DK2825654T3 - SYSTEMS, PROCEDURES, AND COMPOSITIONS WITH CRISPR-CAS COMPONENTS FOR SEQUENCE MANIPULATION. - Google Patents

SYSTEMS, PROCEDURES, AND COMPOSITIONS WITH CRISPR-CAS COMPONENTS FOR SEQUENCE MANIPULATION. Download PDF

Info

Publication number: DK2825654T3
Authority: DK; Denmark
Prior art keywords: sequence; crispr; tracr; target; cas9
Prior art date: 2012-12-12

Application number

DK13812430.0T

Other languages

Danish (da)

English (en)

Inventor

Feng Zhang

David Olivier Bikard

David Benjamin Turitz Cox

Patrick Hsu

Shauiliang Lin

Luciano Marraffini

Randall Jeffrey Platt

Wenyan Jiang

Neville Espi Sanjana

Le Cong

Fei Ran

Original Assignee

Broad Inst Inc

Massachusetts Inst Technology

Harvard College

Univ Rockefeller

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2012-12-12

Filing date

2013-12-12

Publication date

2017-08-21

2013-12-12 Application filed by Broad Inst Inc, Massachusetts Inst Technology, Harvard College, Univ Rockefeller filed Critical Broad Inst Inc

2013-12-12 Priority claimed from PCT/US2013/074611 external-priority patent/WO2014093595A1/en

2017-08-21 Application granted granted Critical

2017-08-21 Publication of DK2825654T3 publication Critical patent/DK2825654T3/en

Links

238000000034 method Methods 0.000 title claims description 144
239000000203 mixture Substances 0.000 title claims description 27
210000004027 cell Anatomy 0.000 claims description 304
108091033409 CRISPR Proteins 0.000 claims description 290
108090000623 proteins and genes Proteins 0.000 claims description 221
102000004190 Enzymes Human genes 0.000 claims description 176
108090000790 Enzymes Proteins 0.000 claims description 176
239000013598 vector Substances 0.000 claims description 160
230000035772 mutation Effects 0.000 claims description 144
238000003776 cleavage reaction Methods 0.000 claims description 123
102000040430 polynucleotide Human genes 0.000 claims description 123
108091033319 polynucleotide Proteins 0.000 claims description 123
239000002157 polynucleotide Substances 0.000 claims description 123
230000007017 scission Effects 0.000 claims description 122
230000014509 gene expression Effects 0.000 claims description 112
210000003527 eukaryotic cell Anatomy 0.000 claims description 104
239000002773 nucleotide Substances 0.000 claims description 80
125000003729 nucleotide group Chemical group 0.000 claims description 76
230000001105 regulatory effect Effects 0.000 claims description 75
108091092236 Chimeric RNA Proteins 0.000 claims description 56
238000002744 homologous recombination Methods 0.000 claims description 54
230000006801 homologous recombination Effects 0.000 claims description 54
241000282414 Homo sapiens Species 0.000 claims description 40
230000030648 nucleus localization Effects 0.000 claims description 28
230000035897 transcription Effects 0.000 claims description 24
238000013518 transcription Methods 0.000 claims description 24
230000002068 genetic effect Effects 0.000 claims description 21
230000009870 specific binding Effects 0.000 claims description 21
230000008569 process Effects 0.000 claims description 19
238000000338 in vitro Methods 0.000 claims description 18
108020004705 Codon Proteins 0.000 claims description 16
238000009825 accumulation Methods 0.000 claims description 12
210000001236 prokaryotic cell Anatomy 0.000 claims description 12
108091026890 Coding region Proteins 0.000 claims description 11
230000030833 cell death Effects 0.000 claims description 7
241000282412 Homo Species 0.000 claims description 3
210000003855 cell nucleus Anatomy 0.000 claims description 2
238000010354 CRISPR gene editing Methods 0.000 claims 12
230000013011 mating Effects 0.000 claims 3
210000004602 germ cell Anatomy 0.000 claims 1
239000000700 radioactive tracer Substances 0.000 claims 1
229940088598 enzyme Drugs 0.000 description 172
108020004414 DNA Proteins 0.000 description 126
230000008685 targeting Effects 0.000 description 97
239000013612 plasmid Substances 0.000 description 96
230000000694 effects Effects 0.000 description 91
108091079001 CRISPR RNA Proteins 0.000 description 70
102000004169 proteins and genes Human genes 0.000 description 67
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 65
239000000047 product Substances 0.000 description 65
125000006850 spacer group Chemical group 0.000 description 65
235000018102 proteins Nutrition 0.000 description 62
238000003556 assay Methods 0.000 description 55
150000007523 nucleic acids Chemical class 0.000 description 54
108091032973 (ribonucleotides)n+m Proteins 0.000 description 49
238000010362 genome editing Methods 0.000 description 49
201000010099 disease Diseases 0.000 description 45
108020005004 Guide RNA Proteins 0.000 description 42
238000012217 deletion Methods 0.000 description 41
230000009466 transformation Effects 0.000 description 41
108010077850 Nuclear Localization Signals Proteins 0.000 description 40
230000037430 deletion Effects 0.000 description 40
238000005516 engineering process Methods 0.000 description 40
102000039446 nucleic acids Human genes 0.000 description 39
108020004707 nucleic acids Proteins 0.000 description 39
241000588724 Escherichia coli Species 0.000 description 38
238000003780 insertion Methods 0.000 description 38
230000001404 mediated effect Effects 0.000 description 38
230000037431 insertion Effects 0.000 description 37
108091034117 Oligonucleotide Proteins 0.000 description 35
101710163270 Nuclease Proteins 0.000 description 34
229930027917 kanamycin Natural products 0.000 description 33
229960000318 kanamycin Drugs 0.000 description 33
SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 33
229930182823 kanamycin A Natural products 0.000 description 33
241000193996 Streptococcus pyogenes Species 0.000 description 32
230000006798 recombination Effects 0.000 description 32
238000005215 recombination Methods 0.000 description 32
150000001413 amino acids Chemical class 0.000 description 31
UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 30
102100023823 Homeobox protein EMX1 Human genes 0.000 description 28
101001048956 Homo sapiens Homeobox protein EMX1 Proteins 0.000 description 28
239000013604 expression vector Substances 0.000 description 28
239000000523 sample Substances 0.000 description 28
238000004458 analytical method Methods 0.000 description 27
238000013461 design Methods 0.000 description 27
ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 26
210000004940 nucleus Anatomy 0.000 description 25
238000011144 upstream manufacturing Methods 0.000 description 25
241000320123 Streptococcus pyogenes M1 GAS Species 0.000 description 24
235000001014 amino acid Nutrition 0.000 description 24
239000000499 gel Substances 0.000 description 24
108091028043 Nucleic acid sequence Proteins 0.000 description 23
230000004048 modification Effects 0.000 description 23
238000012986 modification Methods 0.000 description 23
108010025678 empty spiracles homeobox proteins Proteins 0.000 description 22
238000002474 experimental method Methods 0.000 description 22
101150087718 srtA gene Proteins 0.000 description 22
238000012163 sequencing technique Methods 0.000 description 21
238000001890 transfection Methods 0.000 description 21
108091093088 Amplicon Proteins 0.000 description 20
241000196324 Embryophyta Species 0.000 description 20
230000027455 binding Effects 0.000 description 20
WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 20
208000035475 disorder Diseases 0.000 description 20
108010008532 Deoxyribonuclease I Proteins 0.000 description 19
102000007260 Deoxyribonuclease I Human genes 0.000 description 19
238000004422 calculation algorithm Methods 0.000 description 19
229960005091 chloramphenicol Drugs 0.000 description 19
101150098466 rpsL gene Proteins 0.000 description 19
101100478373 Bacillus subtilis (strain 168) srtD gene Proteins 0.000 description 18
230000001580 bacterial effect Effects 0.000 description 18
238000012360 testing method Methods 0.000 description 18
230000003612 virological effect Effects 0.000 description 18
210000004962 mammalian cell Anatomy 0.000 description 17
210000001519 tissue Anatomy 0.000 description 17
241000894006 Bacteria Species 0.000 description 16
241000699666 Mus <mouse, genus> Species 0.000 description 16
241000194020 Streptococcus thermophilus Species 0.000 description 16
101150087081 bgaA gene Proteins 0.000 description 16
108020004999 messenger RNA Proteins 0.000 description 16
108010005774 beta-Galactosidase Proteins 0.000 description 15
230000015572 biosynthetic process Effects 0.000 description 15
230000000295 complement effect Effects 0.000 description 15
229960005322 streptomycin Drugs 0.000 description 15
102100026189 Beta-galactosidase Human genes 0.000 description 14
230000007018 DNA scission Effects 0.000 description 14
238000000636 Northern blotting Methods 0.000 description 14
241001633172 Streptococcus thermophilus LMD-9 Species 0.000 description 14
230000005782 double-strand break Effects 0.000 description 14
230000006780 non-homologous end joining Effects 0.000 description 14
239000000872 buffer Substances 0.000 description 13
229960003276 erythromycin Drugs 0.000 description 13
238000009396 hybridization Methods 0.000 description 13
108010035563 Chloramphenicol O-acetyltransferase Proteins 0.000 description 12
241000193998 Streptococcus pneumoniae Species 0.000 description 12
101000910046 Streptococcus thermophilus (strain ATCC BAA-491 / LMD-9) CRISPR-associated endonuclease Cas9 1 Proteins 0.000 description 12
239000012634 fragment Substances 0.000 description 12
230000006870 function Effects 0.000 description 12
230000004927 fusion Effects 0.000 description 12
238000010453 CRISPR/Cas method Methods 0.000 description 11
102000053602 DNA Human genes 0.000 description 11
JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 11
238000000137 annealing Methods 0.000 description 11
101150038500 cas9 gene Proteins 0.000 description 11
238000010367 cloning Methods 0.000 description 11
102000037865 fusion proteins Human genes 0.000 description 11
108020001507 fusion proteins Proteins 0.000 description 11
238000001415 gene therapy Methods 0.000 description 11
230000001965 increasing effect Effects 0.000 description 11
230000007246 mechanism Effects 0.000 description 11
230000036961 partial effect Effects 0.000 description 11
108090000765 processed proteins & peptides Proteins 0.000 description 11
238000011160 research Methods 0.000 description 11
238000006467 substitution reaction Methods 0.000 description 11
241000702421 Dependoparvovirus Species 0.000 description 10
101000706121 Homo sapiens Parvalbumin alpha Proteins 0.000 description 10
238000013459 approach Methods 0.000 description 10
239000003795 chemical substances by application Substances 0.000 description 10
238000001514 detection method Methods 0.000 description 10
230000037361 pathway Effects 0.000 description 10
102000004196 processed proteins & peptides Human genes 0.000 description 10
230000008439 repair process Effects 0.000 description 10
230000002441 reversible effect Effects 0.000 description 10
238000007400 DNA extraction Methods 0.000 description 9
241001465754 Metazoa Species 0.000 description 9
108091027544 Subgenomic mRNA Proteins 0.000 description 9
230000036039 immunity Effects 0.000 description 9
230000006698 induction Effects 0.000 description 9
239000002609 medium Substances 0.000 description 9
238000012545 processing Methods 0.000 description 9
238000011002 quantification Methods 0.000 description 9
108700028369 Alleles Proteins 0.000 description 8
101100118093 Drosophila melanogaster eEF1alpha2 gene Proteins 0.000 description 8
102100030856 Myoglobin Human genes 0.000 description 8
230000008901 benefit Effects 0.000 description 8
230000002759 chromosomal effect Effects 0.000 description 8
230000001419 dependent effect Effects 0.000 description 8
239000003623 enhancer Substances 0.000 description 8
238000001727 in vivo Methods 0.000 description 8
230000001939 inductive effect Effects 0.000 description 8
238000005457 optimization Methods 0.000 description 8
238000004806 packaging method and process Methods 0.000 description 8
230000002103 transcriptional effect Effects 0.000 description 8
108091033380 Coding strand Proteins 0.000 description 7
239000006144 Dulbecco’s modiﬁed Eagle's medium Substances 0.000 description 7
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 7
238000010222 PCR analysis Methods 0.000 description 7
108010008281 Recombinant Fusion Proteins Proteins 0.000 description 7
102000007056 Recombinant Fusion Proteins Human genes 0.000 description 7
108091081062 Repeated sequence (DNA) Proteins 0.000 description 7
108091028113 Trans-activating crRNA Proteins 0.000 description 7
101150055766 cat gene Proteins 0.000 description 7
238000010276 construction Methods 0.000 description 7
230000003247 decreasing effect Effects 0.000 description 7
238000012350 deep sequencing Methods 0.000 description 7
230000002255 enzymatic effect Effects 0.000 description 7
229910052739 hydrogen Inorganic materials 0.000 description 7
239000012528 membrane Substances 0.000 description 7
244000052769 pathogen Species 0.000 description 7
230000009467 reduction Effects 0.000 description 7
239000000243 solution Substances 0.000 description 7
208000024891 symptom Diseases 0.000 description 7
239000013603 viral vector Substances 0.000 description 7
238000010446 CRISPR interference Methods 0.000 description 6
108700010070 Codon Usage Proteins 0.000 description 6
238000011529 RT qPCR Methods 0.000 description 6
241000700605 Viruses Species 0.000 description 6
230000000692 anti-sense effect Effects 0.000 description 6
238000004113 cell culture Methods 0.000 description 6
230000005754 cellular signaling Effects 0.000 description 6
239000003153 chemical reaction reagent Substances 0.000 description 6
210000000349 chromosome Anatomy 0.000 description 6
238000009826 distribution Methods 0.000 description 6
230000034431 double-strand break repair via homologous recombination Effects 0.000 description 6
238000003205 genotyping method Methods 0.000 description 6
UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 6
210000000987 immune system Anatomy 0.000 description 6
230000010354 integration Effects 0.000 description 6
230000003993 interaction Effects 0.000 description 6
239000003550 marker Substances 0.000 description 6
231100000350 mutagenesis Toxicity 0.000 description 6
238000003199 nucleic acid amplification method Methods 0.000 description 6
229920001184 polypeptide Polymers 0.000 description 6
239000002243 precursor Substances 0.000 description 6
230000010076 replication Effects 0.000 description 6
230000001177 retroviral effect Effects 0.000 description 6
241000894007 species Species 0.000 description 6
241000701161 unidentified adenovirus Species 0.000 description 6
101150069031 CSN2 gene Proteins 0.000 description 5
241000701022 Cytomegalovirus Species 0.000 description 5
102000004533 Endonucleases Human genes 0.000 description 5
108010042407 Endonucleases Proteins 0.000 description 5
108010043121 Green Fluorescent Proteins Proteins 0.000 description 5
102000004144 Green Fluorescent Proteins Human genes 0.000 description 5
208000026350 Inborn Genetic disease Diseases 0.000 description 5
241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 5
241000124008 Mammalia Species 0.000 description 5
101100101250 Mus musculus Th gene Proteins 0.000 description 5
108700020796 Oncogene Proteins 0.000 description 5
241000194017 Streptococcus Species 0.000 description 5
239000002253 acid Substances 0.000 description 5
230000004913 activation Effects 0.000 description 5
230000003044 adaptive effect Effects 0.000 description 5
230000003321 amplification Effects 0.000 description 5
210000004899 c-terminal region Anatomy 0.000 description 5
150000001875 compounds Chemical class 0.000 description 5
239000003814 drug Substances 0.000 description 5
208000016361 genetic disease Diseases 0.000 description 5
239000001257 hydrogen Substances 0.000 description 5
210000003734 kidney Anatomy 0.000 description 5
238000004519 manufacturing process Methods 0.000 description 5
-1 mutant forms thereof Proteins 0.000 description 5
230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 5
238000000746 purification Methods 0.000 description 5
229960000268 spectinomycin Drugs 0.000 description 5
UNFWWIHTNXNPBV-WXKVUWSESA-N spectinomycin Chemical compound O([C@@H]1[C@@H](NC)[C@@H](O)[C@H]([C@@H]([C@H]1O1)O)NC)[C@]2(O)[C@H]1O[C@H](C)CC2=O UNFWWIHTNXNPBV-WXKVUWSESA-N 0.000 description 5
229940031000 streptococcus pneumoniae Drugs 0.000 description 5
238000012546 transfer Methods 0.000 description 5
230000009261 transgenic effect Effects 0.000 description 5
230000014616 translation Effects 0.000 description 5
241001430294 unidentified retrovirus Species 0.000 description 5
102000040650 (ribonucleotides)n+m Human genes 0.000 description 4
HJCMDXDYPOUFDY-WHFBIAKZSA-N Ala-Gln Chemical compound C[C@H](N)C(=O)N[C@H](C(O)=O)CCC(N)=O HJCMDXDYPOUFDY-WHFBIAKZSA-N 0.000 description 4
102100033312 Alpha-2-macroglobulin Human genes 0.000 description 4
101000651036 Arabidopsis thaliana Galactolipid galactosyltransferase SFR2, chloroplastic Proteins 0.000 description 4
108091032955 Bacterial small RNA Proteins 0.000 description 4
108091003079 Bovine Serum Albumin Proteins 0.000 description 4
101710170303 Chromodomain-helicase-DNA-binding protein 8 Proteins 0.000 description 4
238000001712 DNA sequencing Methods 0.000 description 4
108010070675 Glutathione transferase Proteins 0.000 description 4
102100029100 Hematopoietic prostaglandin D synthase Human genes 0.000 description 4
108091027305 Heteroduplex Proteins 0.000 description 4
241000238631 Hexapoda Species 0.000 description 4
101000635854 Homo sapiens Myoglobin Proteins 0.000 description 4
101000891092 Homo sapiens TAR DNA-binding protein 43 Proteins 0.000 description 4
101000687905 Homo sapiens Transcription factor SOX-2 Proteins 0.000 description 4
241000272168 Laridae Species 0.000 description 4
239000012097 Lipofectamine 2000 Substances 0.000 description 4
206010028980 Neoplasm Diseases 0.000 description 4
108020004711 Nucleic Acid Probes Proteins 0.000 description 4
229930182555 Penicillin Natural products 0.000 description 4
JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 4
102100033616 Phospholipid-transporting ATPase ABCA1 Human genes 0.000 description 4
108010015078 Pregnancy-Associated alpha 2-Macroglobulins Proteins 0.000 description 4
241000700159 Rattus Species 0.000 description 4
102100030547 Serotonin N-acetyltransferase Human genes 0.000 description 4
241000694196 Streptococcus pneumoniae R6 Species 0.000 description 4
241001505901 Streptococcus sp. 'group A' Species 0.000 description 4
108010021188 Superoxide Dismutase-1 Proteins 0.000 description 4
102100038836 Superoxide dismutase [Cu-Zn] Human genes 0.000 description 4
238000010459 TALEN Methods 0.000 description 4
102100040347 TAR DNA-binding protein 43 Human genes 0.000 description 4
108010043645 Transcription Activator-Like Effector Nucleases Proteins 0.000 description 4
108010073062 Transcription Activator-Like Effectors Proteins 0.000 description 4
108020004566 Transfer RNA Proteins 0.000 description 4
101710176279 Tubulin beta-2 chain Proteins 0.000 description 4
108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 4
108010073925 Vascular Endothelial Growth Factor B Proteins 0.000 description 4
102000009520 Vascular Endothelial Growth Factor C Human genes 0.000 description 4
108010073923 Vascular Endothelial Growth Factor C Proteins 0.000 description 4
102100039037 Vascular endothelial growth factor A Human genes 0.000 description 4
102100038217 Vascular endothelial growth factor B Human genes 0.000 description 4
108010017070 Zinc Finger Nucleases Proteins 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
239000013543 active substance Substances 0.000 description 4
201000008266 amyotrophic lateral sclerosis type 2 Diseases 0.000 description 4
208000029560 autism spectrum disease Diseases 0.000 description 4
230000009286 beneficial effect Effects 0.000 description 4
230000008238 biochemical pathway Effects 0.000 description 4
238000006243 chemical reaction Methods 0.000 description 4
238000012761 co-transfection Methods 0.000 description 4
230000007547 defect Effects 0.000 description 4
230000029087 digestion Effects 0.000 description 4
229940079593 drug Drugs 0.000 description 4
238000006911 enzymatic reaction Methods 0.000 description 4
206010015037 epilepsy Diseases 0.000 description 4
239000012091 fetal bovine serum Substances 0.000 description 4
238000010363 gene targeting Methods 0.000 description 4
239000005090 green fluorescent protein Substances 0.000 description 4
230000036541 health Effects 0.000 description 4
238000003384 imaging method Methods 0.000 description 4
238000011534 incubation Methods 0.000 description 4
208000032799 juvenile amyotrophic lateral sclerosis type 2 Diseases 0.000 description 4
238000001638 lipofection Methods 0.000 description 4
230000035800 maturation Effects 0.000 description 4
238000010369 molecular cloning Methods 0.000 description 4
238000002703 mutagenesis Methods 0.000 description 4
239000013642 negative control Substances 0.000 description 4
239000002853 nucleic acid probe Substances 0.000 description 4
229940049954 penicillin Drugs 0.000 description 4
229920002401 polyacrylamide Polymers 0.000 description 4
229920000642 polymer Polymers 0.000 description 4
238000003259 recombinant expression Methods 0.000 description 4
230000011664 signaling Effects 0.000 description 4
239000004055 small Interfering RNA Substances 0.000 description 4
230000001225 therapeutic effect Effects 0.000 description 4
230000005026 transcription initiation Effects 0.000 description 4
230000005030 transcription termination Effects 0.000 description 4
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
108020005345 3' Untranslated Regions Proteins 0.000 description 3
102100035923 4-aminobutyrate aminotransferase, mitochondrial Human genes 0.000 description 3
239000013607 AAV vector Substances 0.000 description 3
HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 3
208000024827 Alzheimer disease Diseases 0.000 description 3
108010039224 Amidophosphoribosyltransferase Proteins 0.000 description 3
241000203069 Archaea Species 0.000 description 3
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 3
102100025064 Cellular tumor antigen p53 Human genes 0.000 description 3
102000000018 Chemokine CCL2 Human genes 0.000 description 3
241000195597 Chlamydomonas reinhardtii Species 0.000 description 3
102100038165 Chromodomain-helicase-DNA-binding protein 8 Human genes 0.000 description 3
101710177611 DNA polymerase II large subunit Proteins 0.000 description 3
101710184669 DNA polymerase II small subunit Proteins 0.000 description 3
241000252212 Danio rerio Species 0.000 description 3
241000588722 Escherichia Species 0.000 description 3
108700024394 Exon Proteins 0.000 description 3
241000282326 Felis catus Species 0.000 description 3
101150106478 GPS1 gene Proteins 0.000 description 3
108700039691 Genetic Promoter Regions Proteins 0.000 description 3
239000007995 HEPES buffer Substances 0.000 description 3
101000721661 Homo sapiens Cellular tumor antigen p53 Proteins 0.000 description 3
102100021244 Integral membrane protein GPR180 Human genes 0.000 description 3
241000713666 Lentivirus Species 0.000 description 3
102000018697 Membrane Proteins Human genes 0.000 description 3
108010052285 Membrane Proteins Proteins 0.000 description 3
101100219625 Mus musculus Casd1 gene Proteins 0.000 description 3
108020004485 Nonsense Codon Proteins 0.000 description 3
102000002488 Nucleoplasmin Human genes 0.000 description 3
241000283973 Oryctolagus cuniculus Species 0.000 description 3
101100273635 Rattus norvegicus Ccn5 gene Proteins 0.000 description 3
102000003661 Ribonuclease III Human genes 0.000 description 3
108010057163 Ribonuclease III Proteins 0.000 description 3
241000714474 Rous sarcoma virus Species 0.000 description 3
241000700584 Simplexvirus Species 0.000 description 3
241000205101 Sulfolobus Species 0.000 description 3
108010006785 Taq Polymerase Proteins 0.000 description 3
230000002159 abnormal effect Effects 0.000 description 3
208000021841 acute erythroid leukemia Diseases 0.000 description 3
230000006978 adaptation Effects 0.000 description 3
229960000723 ampicillin Drugs 0.000 description 3
AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 3
210000004102 animal cell Anatomy 0.000 description 3
230000008436 biogenesis Effects 0.000 description 3
210000004369 blood Anatomy 0.000 description 3
239000008280 blood Substances 0.000 description 3
230000003197 catalytic effect Effects 0.000 description 3
230000008859 change Effects 0.000 description 3
230000001332 colony forming effect Effects 0.000 description 3
230000009918 complex formation Effects 0.000 description 3
101150055601 cops2 gene Proteins 0.000 description 3
108010082025 cyan fluorescent protein Proteins 0.000 description 3
230000034994 death Effects 0.000 description 3
230000007123 defense Effects 0.000 description 3
238000011156 evaluation Methods 0.000 description 3
210000002950 fibroblast Anatomy 0.000 description 3
238000001914 filtration Methods 0.000 description 3
238000003209 gene knockout Methods 0.000 description 3
238000010353 genetic engineering Methods 0.000 description 3
102000049240 human PVALB Human genes 0.000 description 3
230000000415 inactivating effect Effects 0.000 description 3
230000002147 killing effect Effects 0.000 description 3
230000000670 limiting effect Effects 0.000 description 3
239000002502 liposome Substances 0.000 description 3
238000011068 loading method Methods 0.000 description 3
108060005597 nucleoplasmin Proteins 0.000 description 3
230000001717 pathogenic effect Effects 0.000 description 3
238000013081 phylogenetic analysis Methods 0.000 description 3
238000003752 polymerase chain reaction Methods 0.000 description 3
238000002360 preparation method Methods 0.000 description 3
108020001580 protein domains Proteins 0.000 description 3
230000002829 reductive effect Effects 0.000 description 3
238000007894 restriction fragment length polymorphism technique Methods 0.000 description 3
238000007480 sanger sequencing Methods 0.000 description 3
201000000980 schizophrenia Diseases 0.000 description 3
208000011580 syndromic disease Diseases 0.000 description 3
230000009897 systematic effect Effects 0.000 description 3
238000012353 t test Methods 0.000 description 3
RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical class CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 3
238000013519 translation Methods 0.000 description 3
229910021642 ultra pure water Inorganic materials 0.000 description 3
239000012498 ultrapure water Substances 0.000 description 3
241000701447 unidentified baculovirus Species 0.000 description 3
241001515965 unidentified phage Species 0.000 description 3
238000010200 validation analysis Methods 0.000 description 3
238000012800 visualization Methods 0.000 description 3
102100023912 40S ribosomal protein S12 Human genes 0.000 description 2
FVFVNNKYKYZTJU-UHFFFAOYSA-N 6-chloro-1,3,5-triazine-2,4-diamine Chemical compound NC1=NC(N)=NC(Cl)=N1 FVFVNNKYKYZTJU-UHFFFAOYSA-N 0.000 description 2
101150092476 ABCA1 gene Proteins 0.000 description 2
102100024378 AF4/FMR2 family member 2 Human genes 0.000 description 2
108700005241 ATP Binding Cassette Transporter 1 Proteins 0.000 description 2
102100036618 ATP-binding cassette sub-family A member 13 Human genes 0.000 description 2
102100033618 ATP-binding cassette sub-family A member 2 Human genes 0.000 description 2
229920001817 Agar Polymers 0.000 description 2
102100024401 Alpha-1D adrenergic receptor Human genes 0.000 description 2
102100022815 Alpha-2A adrenergic receptor Human genes 0.000 description 2
102100025983 Alpha-2C adrenergic receptor Human genes 0.000 description 2
108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 description 2
102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 description 2
102100032187 Androgen receptor Human genes 0.000 description 2
102100029470 Apolipoprotein E Human genes 0.000 description 2
108010074515 Arylalkylamine N-Acetyltransferase Proteins 0.000 description 2
102000007370 Ataxin2 Human genes 0.000 description 2
108010032951 Ataxin2 Proteins 0.000 description 2
102100021257 Beta-secretase 1 Human genes 0.000 description 2
101710150192 Beta-secretase 1 Proteins 0.000 description 2
208000014644 Brain disease Diseases 0.000 description 2
101710155857 C-C motif chemokine 2 Proteins 0.000 description 2
101000909256 Caldicellulosiruptor bescii (strain ATCC BAA-1888 / DSM 6725 / Z-1320) DNA polymerase I Proteins 0.000 description 2
241000195585 Chlamydomonas Species 0.000 description 2
206010010904 Convulsion Diseases 0.000 description 2
239000004971 Cross linker Substances 0.000 description 2
241000195493 Cryptophyta Species 0.000 description 2
230000007067 DNA methylation Effects 0.000 description 2
230000033616 DNA repair Effects 0.000 description 2
230000004543 DNA replication Effects 0.000 description 2
230000006820 DNA synthesis Effects 0.000 description 2
230000004568 DNA-binding Effects 0.000 description 2
102000001301 EGF receptor Human genes 0.000 description 2
108060006698 EGF receptor Proteins 0.000 description 2
101100275895 Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139) csnB gene Proteins 0.000 description 2
102100030013 Endoribonuclease Human genes 0.000 description 2
108010093099 Endoribonucleases Proteins 0.000 description 2
101100326871 Escherichia coli (strain K12) ygbF gene Proteins 0.000 description 2
101100438439 Escherichia coli (strain K12) ygbT gene Proteins 0.000 description 2
241000206602 Eukaryota Species 0.000 description 2
241000192125 Firmicutes Species 0.000 description 2
108010032606 Fragile X Mental Retardation Protein Proteins 0.000 description 2
102000003869 Frataxin Human genes 0.000 description 2
108090000217 Frataxin Proteins 0.000 description 2
208000024412 Friedreich ataxia Diseases 0.000 description 2
241000233866 Fungi Species 0.000 description 2
102100024375 Gamma-glutamylaminecyclotransferase Human genes 0.000 description 2
101710201613 Gamma-glutamylaminecyclotransferase Proteins 0.000 description 2
102100033713 Gamma-secretase subunit APH-1B Human genes 0.000 description 2
102100028260 Gamma-secretase subunit PEN-2 Human genes 0.000 description 2
241000713813 Gibbon ape leukemia virus Species 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
102100040870 Glycine amidinotransferase, mitochondrial Human genes 0.000 description 2
208000032007 Glycogen storage disease due to acid maltase deficiency Diseases 0.000 description 2
206010053185 Glycogen storage disease type II Diseases 0.000 description 2
101710154606 Hemagglutinin Proteins 0.000 description 2
101001000686 Homo sapiens 4-aminobutyrate aminotransferase, mitochondrial Proteins 0.000 description 2
101000929660 Homo sapiens ATP-binding cassette sub-family A member 13 Proteins 0.000 description 2
101000801645 Homo sapiens ATP-binding cassette sub-family A member 2 Proteins 0.000 description 2
101000756842 Homo sapiens Alpha-2A adrenergic receptor Proteins 0.000 description 2
101000720032 Homo sapiens Alpha-2C adrenergic receptor Proteins 0.000 description 2
101000733778 Homo sapiens Gamma-secretase subunit APH-1B Proteins 0.000 description 2
101000579663 Homo sapiens Gamma-secretase subunit PEN-2 Proteins 0.000 description 2
101000893303 Homo sapiens Glycine amidinotransferase, mitochondrial Proteins 0.000 description 2
101000957437 Homo sapiens Mitochondrial carnitine/acylcarnitine carrier protein Proteins 0.000 description 2
101000801684 Homo sapiens Phospholipid-transporting ATPase ABCA1 Proteins 0.000 description 2
101000801640 Homo sapiens Phospholipid-transporting ATPase ABCA3 Proteins 0.000 description 2
101001135385 Homo sapiens Prostacyclin synthase Proteins 0.000 description 2
101000801643 Homo sapiens Retinal-specific phospholipid-transporting ATPase ABCA4 Proteins 0.000 description 2
101100257362 Homo sapiens SOX2 gene Proteins 0.000 description 2
101000785063 Homo sapiens Serine-protein kinase ATM Proteins 0.000 description 2
101000904787 Homo sapiens Serine/threonine-protein kinase ATR Proteins 0.000 description 2
101000652292 Homo sapiens Serotonin N-acetyltransferase Proteins 0.000 description 2
108010001336 Horseradish Peroxidase Proteins 0.000 description 2
241000725303 Human immunodeficiency virus Species 0.000 description 2
208000023105 Huntington disease Diseases 0.000 description 2
206010061218 Inflammation Diseases 0.000 description 2
108010015268 Integration Host Factors Proteins 0.000 description 2
102000004388 Interleukin-4 Human genes 0.000 description 2
108090000978 Interleukin-4 Proteins 0.000 description 2
108091092195 Intron Proteins 0.000 description 2
102100036600 Kynurenine/alpha-aminoadipate aminotransferase, mitochondrial Human genes 0.000 description 2
208000005870 Lafora disease Diseases 0.000 description 2
208000014161 Lafora myoclonic epilepsy Diseases 0.000 description 2
101710128836 Large T antigen Proteins 0.000 description 2
208000009625 Lesch-Nyhan syndrome Diseases 0.000 description 2
235000007688 Lycopersicon esculentum Nutrition 0.000 description 2
108091077181 M protein family Proteins 0.000 description 2
101710175625 Maltose/maltodextrin-binding periplasmic protein Proteins 0.000 description 2
102100025169 Max-binding protein MNT Human genes 0.000 description 2
238000007476 Maximum Likelihood Methods 0.000 description 2
241001599018 Melanogaster Species 0.000 description 2
102000000440 Melanoma-associated antigen Human genes 0.000 description 2
108050008953 Melanoma-associated antigen Proteins 0.000 description 2
208000036626 Mental retardation Diseases 0.000 description 2
102100038738 Mitochondrial carnitine/acylcarnitine carrier protein Human genes 0.000 description 2
241001529936 Murinae Species 0.000 description 2
241000714177 Murine leukemia virus Species 0.000 description 2
241000699670 Mus sp. Species 0.000 description 2
108010052185 Myotonin-Protein Kinase Proteins 0.000 description 2
102100022437 Myotonin-protein kinase Human genes 0.000 description 2
102100028719 NEDD8-activating enzyme E1 catalytic subunit Human genes 0.000 description 2
108700019961 Neoplasm Genes Proteins 0.000 description 2
102000048850 Neoplasm Genes Human genes 0.000 description 2
208000012902 Nervous system disease Diseases 0.000 description 2
108010040718 Neurokinin-1 Receptors Proteins 0.000 description 2
208000025966 Neurological disease Diseases 0.000 description 2
208000002537 Neuronal Ceroid-Lipofuscinoses Diseases 0.000 description 2
102100022397 Nitric oxide synthase, brain Human genes 0.000 description 2
101710093908 Outer capsid protein VP4 Proteins 0.000 description 2
101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 2
238000012408 PCR amplification Methods 0.000 description 2
208000018737 Parkinson disease Diseases 0.000 description 2
206010057249 Phagocytosis Diseases 0.000 description 2
102100033623 Phospholipid-transporting ATPase ABCA3 Human genes 0.000 description 2
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
108010021757 Polynucleotide 5'-Hydroxyl-Kinase Proteins 0.000 description 2
102000008422 Polynucleotide 5'-hydroxyl-kinase Human genes 0.000 description 2
102100022033 Presenilin-1 Human genes 0.000 description 2
102100022036 Presenilin-2 Human genes 0.000 description 2
102000029797 Prion Human genes 0.000 description 2
108091000054 Prion Proteins 0.000 description 2
208000024777 Prion disease Diseases 0.000 description 2
102100033075 Prostacyclin synthase Human genes 0.000 description 2
101710176177 Protein A56 Proteins 0.000 description 2
102100034180 Protein AATF Human genes 0.000 description 2
101710155502 Protein AATF Proteins 0.000 description 2
108700020978 Proto-Oncogene Proteins 0.000 description 2
102000052575 Proto-Oncogene Human genes 0.000 description 2
101000902592 Pyrococcus furiosus (strain ATCC 43587 / DSM 3638 / JCM 8422 / Vc1) DNA polymerase Proteins 0.000 description 2
102100038188 RNA binding protein fox-1 homolog 1 Human genes 0.000 description 2
108020004511 Recombinant DNA Proteins 0.000 description 2
108700008625 Reporter Genes Proteins 0.000 description 2
101100273253 Rhizopus niveus RNAP gene Proteins 0.000 description 2
102000004389 Ribonucleoproteins Human genes 0.000 description 2
108010081734 Ribonucleoproteins Proteins 0.000 description 2
240000004808 Saccharomyces cerevisiae Species 0.000 description 2
206010039491 Sarcoma Diseases 0.000 description 2
102100020824 Serine-protein kinase ATM Human genes 0.000 description 2
102100023921 Serine/threonine-protein kinase ATR Human genes 0.000 description 2
241000713311 Simian immunodeficiency virus Species 0.000 description 2
108091027967 Small hairpin RNA Proteins 0.000 description 2
108020004459 Small interfering RNA Proteins 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
240000003768 Solanum lycopersicum Species 0.000 description 2
102000005157 Somatostatin Human genes 0.000 description 2
108010056088 Somatostatin Proteins 0.000 description 2
241000191967 Staphylococcus aureus Species 0.000 description 2
238000000692 Student's t-test Methods 0.000 description 2
102100037346 Substance-P receptor Human genes 0.000 description 2
102100023532 Synaptic functional regulator FMR1 Human genes 0.000 description 2
101100329497 Thermoproteus tenax (strain ATCC 35583 / DSM 2078 / JCM 9277 / NBRC 100435 / Kra 1) cas2 gene Proteins 0.000 description 2
102100036407 Thioredoxin Human genes 0.000 description 2
208000035317 Total hypoxanthine-guanine phosphoribosyl transferase deficiency Diseases 0.000 description 2
108091023040 Transcription factor Proteins 0.000 description 2
102000040945 Transcription factor Human genes 0.000 description 2
102100024270 Transcription factor SOX-2 Human genes 0.000 description 2
108700019146 Transgenes Proteins 0.000 description 2
238000010162 Tukey test Methods 0.000 description 2
102100037160 Ubiquitin-like modifier-activating enzyme 1 Human genes 0.000 description 2
101710191412 Ubiquitin-like modifier-activating enzyme 1 Proteins 0.000 description 2
102100039066 Very low-density lipoprotein receptor Human genes 0.000 description 2
108091093126 WHP Posttrascriptional Response Element Proteins 0.000 description 2
108010091383 Xanthine dehydrogenase Proteins 0.000 description 2
102000005773 Xanthine dehydrogenase Human genes 0.000 description 2
108010093894 Xanthine oxidase Proteins 0.000 description 2
201000004525 Zellweger Syndrome Diseases 0.000 description 2
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
ZKHQWZAMYRWXGA-KNYAHOBESA-N [[(2r,3s,4r,5r)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] dihydroxyphosphoryl hydrogen phosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)O[32P](O)(O)=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KNYAHOBESA-N 0.000 description 2
210000005006 adaptive immune system Anatomy 0.000 description 2
230000004721 adaptive immunity Effects 0.000 description 2
239000008272 agar Substances 0.000 description 2
239000011543 agarose gel Substances 0.000 description 2
206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 2
230000003698 anagen phase Effects 0.000 description 2
238000004873 anchoring Methods 0.000 description 2
108010080146 androgen receptors Proteins 0.000 description 2
239000003242 anti bacterial agent Substances 0.000 description 2
229940088710 antibiotic agent Drugs 0.000 description 2
230000003416 augmentation Effects 0.000 description 2
230000002146 bilateral effect Effects 0.000 description 2
230000003115 biocidal effect Effects 0.000 description 2
230000008827 biological function Effects 0.000 description 2
108091005948 blue fluorescent proteins Proteins 0.000 description 2
201000011510 cancer Diseases 0.000 description 2
101150000705 cas1 gene Proteins 0.000 description 2
101150117416 cas2 gene Proteins 0.000 description 2
108020001778 catalytic domains Proteins 0.000 description 2
210000002421 cell wall Anatomy 0.000 description 2
230000001413 cellular effect Effects 0.000 description 2
208000003131 cerebrooculofacioskeletal syndrome 1 Diseases 0.000 description 2
101150085358 chd8 gene Proteins 0.000 description 2
230000004186 co-expression Effects 0.000 description 2
239000003086 colorant Substances 0.000 description 2
239000002299 complementary DNA Substances 0.000 description 2
230000021615 conjugation Effects 0.000 description 2
238000005520 cutting process Methods 0.000 description 2
230000005860 defense response to virus Effects 0.000 description 2
230000002950 deficient Effects 0.000 description 2
230000002939 deleterious effect Effects 0.000 description 2
LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
230000012361 double-strand break repair Effects 0.000 description 2
238000004520 electroporation Methods 0.000 description 2
210000001671 embryonic stem cell Anatomy 0.000 description 2
238000010195 expression analysis Methods 0.000 description 2
108091006047 fluorescent proteins Proteins 0.000 description 2
102000034287 fluorescent proteins Human genes 0.000 description 2
230000037433 frameshift Effects 0.000 description 2
238000003633 gene expression assay Methods 0.000 description 2
238000012252 genetic analysis Methods 0.000 description 2
230000007614 genetic variation Effects 0.000 description 2
238000012268 genome sequencing Methods 0.000 description 2
201000004502 glycogen storage disease II Diseases 0.000 description 2
239000000185 hemagglutinin Substances 0.000 description 2
102000047444 human SOX2 Human genes 0.000 description 2
230000001976 improved effect Effects 0.000 description 2
230000006872 improvement Effects 0.000 description 2
230000002779 inactivation Effects 0.000 description 2
230000004054 inflammatory process Effects 0.000 description 2
230000000977 initiatory effect Effects 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
229940028885 interleukin-4 Drugs 0.000 description 2
238000002372 labelling Methods 0.000 description 2
150000002632 lipids Chemical class 0.000 description 2
238000009630 liquid culture Methods 0.000 description 2
210000004185 liver Anatomy 0.000 description 2
208000002780 macular degeneration Diseases 0.000 description 2
230000011987 methylation Effects 0.000 description 2
238000007069 methylation reaction Methods 0.000 description 2
108091070501 miRNA Proteins 0.000 description 2
239000002679 microRNA Substances 0.000 description 2
238000012737 microarray-based gene expression Methods 0.000 description 2
230000033607 mismatch repair Effects 0.000 description 2
238000012243 multiplex automated genomic engineering Methods 0.000 description 2
231100000219 mutagenic Toxicity 0.000 description 2
239000003471 mutagenic agent Substances 0.000 description 2
230000003505 mutagenic effect Effects 0.000 description 2
230000036438 mutation frequency Effects 0.000 description 2
230000009826 neoplastic cell growth Effects 0.000 description 2
210000002569 neuron Anatomy 0.000 description 2
108091027963 non-coding RNA Proteins 0.000 description 2
102000042567 non-coding RNA Human genes 0.000 description 2
210000000496 pancreas Anatomy 0.000 description 2
239000002245 particle Substances 0.000 description 2
230000001575 pathological effect Effects 0.000 description 2
230000008782 phagocytosis Effects 0.000 description 2
239000003016 pheromone Substances 0.000 description 2
239000002953 phosphate buffered saline Substances 0.000 description 2
108010079892 phosphoglycerol kinase Proteins 0.000 description 2
230000026731 phosphorylation Effects 0.000 description 2
238000006366 phosphorylation reaction Methods 0.000 description 2
239000013600 plasmid vector Substances 0.000 description 2
238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 2
239000013641 positive control Substances 0.000 description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
230000000069 prophylactic effect Effects 0.000 description 2
238000001243 protein synthesis Methods 0.000 description 2
230000003252 repetitive effect Effects 0.000 description 2
230000004044 response Effects 0.000 description 2
230000000717 retained effect Effects 0.000 description 2
108010092841 ribosomal protein S12 Proteins 0.000 description 2
102200028670 rs1940475 Human genes 0.000 description 2
239000000344 soap Substances 0.000 description 2
NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 2
229960000553 somatostatin Drugs 0.000 description 2
210000000130 stem cell Anatomy 0.000 description 2
239000006228 supernatant Substances 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
WWJZWCUNLNYYAU-UHFFFAOYSA-N temephos Chemical compound C1=CC(OP(=S)(OC)OC)=CC=C1SC1=CC=C(OP(=S)(OC)OC)C=C1 WWJZWCUNLNYYAU-UHFFFAOYSA-N 0.000 description 2
108060008226 thioredoxin Proteins 0.000 description 2
108091006107 transcriptional repressors Proteins 0.000 description 2
238000010361 transduction Methods 0.000 description 2
230000026683 transduction Effects 0.000 description 2
230000001052 transient effect Effects 0.000 description 2
239000006150 trypticase soy agar Substances 0.000 description 2
230000001018 virulence Effects 0.000 description 2
238000005406 washing Methods 0.000 description 2
108091005957 yellow fluorescent proteins Proteins 0.000 description 2
229910052725 zinc Inorganic materials 0.000 description 2
239000011701 zinc Substances 0.000 description 2
OJHZNMVJJKMFGX-RNWHKREASA-N (4r,4ar,7ar,12bs)-9-methoxy-3-methyl-1,2,4,4a,5,6,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-7-one;2,3-dihydroxybutanedioic acid Chemical compound OC(=O)C(O)C(O)C(O)=O.O=C([C@@H]1O2)CC[C@H]3[C@]4([H])N(C)CC[C@]13C1=C2C(OC)=CC=C1C4 OJHZNMVJJKMFGX-RNWHKREASA-N 0.000 description 1
GUAHPAJOXVYFON-ZETCQYMHSA-N (8S)-8-amino-7-oxononanoic acid zwitterion Chemical compound C[C@H](N)C(=O)CCCCCC(O)=O GUAHPAJOXVYFON-ZETCQYMHSA-N 0.000 description 1
GZCWLCBFPRFLKL-UHFFFAOYSA-N 1-prop-2-ynoxypropan-2-ol Chemical compound CC(O)COCC#C GZCWLCBFPRFLKL-UHFFFAOYSA-N 0.000 description 1
OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
102100039217 3-ketoacyl-CoA thiolase, peroxisomal Human genes 0.000 description 1
FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 1
101710094518 4-aminobutyrate aminotransferase Proteins 0.000 description 1
102100024959 5-hydroxytryptamine receptor 2C Human genes 0.000 description 1
101150020052 AADAT gene Proteins 0.000 description 1
108091022885 ADAM Proteins 0.000 description 1
101710184468 AF4/FMR2 family member 2 Proteins 0.000 description 1
101150037123 APOE gene Proteins 0.000 description 1
102100039601 ARF GTPase-activating protein GIT1 Human genes 0.000 description 1
102220489925 AT-rich interactive domain-containing protein 1B_A11AA_mutation Human genes 0.000 description 1
102100024643 ATP-binding cassette sub-family D member 1 Human genes 0.000 description 1
102100033092 ATP-binding cassette sub-family G member 8 Human genes 0.000 description 1
102000013563 Acid Phosphatase Human genes 0.000 description 1
108010051457 Acid Phosphatase Proteins 0.000 description 1
208000034012 Acid sphingomyelinase deficiency Diseases 0.000 description 1
241000589291 Acinetobacter Species 0.000 description 1
102100036732 Actin, aortic smooth muscle Human genes 0.000 description 1
102100022900 Actin, cytoplasmic 1 Human genes 0.000 description 1
108010085238 Actins Proteins 0.000 description 1
102000008161 Adenosine A3 Receptor Human genes 0.000 description 1
108010060261 Adenosine A3 Receptor Proteins 0.000 description 1
102100036006 Adenosine receptor A3 Human genes 0.000 description 1
201000011452 Adrenoleukodystrophy Diseases 0.000 description 1
241000567147 Aeropyrum Species 0.000 description 1
101150029691 Aff2 gene Proteins 0.000 description 1
241000589158 Agrobacterium Species 0.000 description 1
208000024341 Aicardi syndrome Diseases 0.000 description 1
102000009027 Albumins Human genes 0.000 description 1
108010088751 Albumins Proteins 0.000 description 1
208000011403 Alexander disease Diseases 0.000 description 1
208000006829 Allan-Herndon-Dudley syndrome Diseases 0.000 description 1
KHOITXIGCFIULA-UHFFFAOYSA-N Alophen Chemical compound C1=CC(OC(=O)C)=CC=C1C(C=1N=CC=CC=1)C1=CC=C(OC(C)=O)C=C1 KHOITXIGCFIULA-UHFFFAOYSA-N 0.000 description 1
208000036022 Alpers' disease Diseases 0.000 description 1
101710109805 Alpha-1D adrenergic receptor Proteins 0.000 description 1
208000030894 Alpha-N-acetylgalactosaminidase deficiency type 1 Diseases 0.000 description 1
102100023635 Alpha-fetoprotein Human genes 0.000 description 1
206010068783 Alstroem syndrome Diseases 0.000 description 1
201000005932 Alstrom Syndrome Diseases 0.000 description 1
208000026833 Alzheimer disease 4 Diseases 0.000 description 1
208000031277 Amaurotic familial idiocy Diseases 0.000 description 1
102100022704 Amyloid-beta precursor protein Human genes 0.000 description 1
101710151993 Amyloid-beta precursor protein Proteins 0.000 description 1
241000192542 Anabaena Species 0.000 description 1
108010048154 Angiopoietin-1 Proteins 0.000 description 1
102000009088 Angiopoietin-1 Human genes 0.000 description 1
102100034594 Angiopoietin-1 Human genes 0.000 description 1
101710095339 Apolipoprotein E Proteins 0.000 description 1
241000207208 Aquifex Species 0.000 description 1
101001123982 Arabidopsis thaliana Protochlorophyllide reductase C, chloroplastic Proteins 0.000 description 1
241000205046 Archaeoglobus Species 0.000 description 1
241000238421 Arthropoda Species 0.000 description 1
206010003594 Ataxia telangiectasia Diseases 0.000 description 1
208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 1
208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 1
206010003805 Autism Diseases 0.000 description 1
208000020706 Autistic disease Diseases 0.000 description 1
208000001992 Autosomal Dominant Optic Atrophy Diseases 0.000 description 1
208000026553 Autosomal dominant optic atrophy, classic form Diseases 0.000 description 1
238000012935 Averaging Methods 0.000 description 1
206010063659 Aversion Diseases 0.000 description 1
241000193830 Bacillus <bacterium> Species 0.000 description 1
208000035143 Bacterial infection Diseases 0.000 description 1
201000005943 Barth syndrome Diseases 0.000 description 1
206010061692 Benign muscle neoplasm Diseases 0.000 description 1
BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
206010048409 Brain malformation Diseases 0.000 description 1
102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 1
108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 1
102100035875 C-C chemokine receptor type 5 Human genes 0.000 description 1
101710149870 C-C chemokine receptor type 5 Proteins 0.000 description 1
102100021943 C-C motif chemokine 2 Human genes 0.000 description 1
102000014814 CACNA1C Human genes 0.000 description 1
208000010482 CADASIL Diseases 0.000 description 1
108700013048 CCL2 Proteins 0.000 description 1
101150052909 CCL2 gene Proteins 0.000 description 1
101150083327 CCR2 gene Proteins 0.000 description 1
101150017501 CCR5 gene Proteins 0.000 description 1
238000010356 CRISPR-Cas9 genome editing Methods 0.000 description 1
101710172824 CRISPR-associated endonuclease Cas9 Proteins 0.000 description 1
101150018129 CSF2 gene Proteins 0.000 description 1
101150023944 CXCR5 gene Proteins 0.000 description 1
102100027557 Calcipressin-1 Human genes 0.000 description 1
240000001432 Calendula officinalis Species 0.000 description 1
235000005881 Calendula officinalis Nutrition 0.000 description 1
241000589876 Campylobacter Species 0.000 description 1
208000022526 Canavan disease Diseases 0.000 description 1
241000972912 Canis lupus labradorius Species 0.000 description 1
208000024172 Cardiovascular disease Diseases 0.000 description 1
102000014914 Carrier Proteins Human genes 0.000 description 1
108090000994 Catalytic RNA Proteins 0.000 description 1
102000053642 Catalytic RNA Human genes 0.000 description 1
108090000712 Cathepsin B Proteins 0.000 description 1
102000004225 Cathepsin B Human genes 0.000 description 1
102100021633 Cathepsin B Human genes 0.000 description 1
108090000625 Cathepsin K Proteins 0.000 description 1
102000004171 Cathepsin K Human genes 0.000 description 1
102100024940 Cathepsin K Human genes 0.000 description 1
241000282693 Cercopithecidae Species 0.000 description 1
208000033221 Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy Diseases 0.000 description 1
208000033935 Cerebral autosomal dominant arteriopathy-subcortical infarcts-leukoencephalopathy Diseases 0.000 description 1
241000191366 Chlorobium Species 0.000 description 1
241000588881 Chromobacterium Species 0.000 description 1
241000193403 Clostridium Species 0.000 description 1
101100007328 Cocos nucifera COS-1 gene Proteins 0.000 description 1
102000008186 Collagen Human genes 0.000 description 1
108010035532 Collagen Proteins 0.000 description 1
102100033601 Collagen alpha-1(I) chain Human genes 0.000 description 1
206010010099 Combined immunodeficiency Diseases 0.000 description 1
101710082261 Competence-stimulating peptide Proteins 0.000 description 1
102100027826 Complexin-1 Human genes 0.000 description 1
208000037141 Congenital muscular dystrophy, Fukuyama type Diseases 0.000 description 1
102000020856 Copper Transport Proteins Human genes 0.000 description 1
108091004554 Copper Transport Proteins Proteins 0.000 description 1
201000009343 Cornelia de Lange syndrome Diseases 0.000 description 1
241000186216 Corynebacterium Species 0.000 description 1
101150074775 Csf1 gene Proteins 0.000 description 1
101150074155 DHFR gene Proteins 0.000 description 1
230000005971 DNA damage repair Effects 0.000 description 1
108010063593 DNA modification methylase SssI Proteins 0.000 description 1
241000450599 DNA viruses Species 0.000 description 1
108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
208000003471 De Lange Syndrome Diseases 0.000 description 1
206010012289 Dementia Diseases 0.000 description 1
206010012335 Dependence Diseases 0.000 description 1
241000605716 Desulfovibrio Species 0.000 description 1
101100257467 Dictyostelium discoideum spcs1 gene Proteins 0.000 description 1
208000004986 Diffuse Cerebral Sclerosis of Schilder Diseases 0.000 description 1
206010061818 Disease progression Diseases 0.000 description 1
102100022825 Disintegrin and metalloproteinase domain-containing protein 22 Human genes 0.000 description 1
102100022273 Disrupted in schizophrenia 1 protein Human genes 0.000 description 1
102100035966 DnaJ homolog subfamily A member 2 Human genes 0.000 description 1
201000007547 Dravet syndrome Diseases 0.000 description 1
102100028554 Dual specificity tyrosine-phosphorylation-regulated kinase 1A Human genes 0.000 description 1
108010040648 Dyrk kinase Proteins 0.000 description 1
102100038132 Endogenous retrovirus group K member 6 Pro protein Human genes 0.000 description 1
108010013369 Enteropeptidase Proteins 0.000 description 1
102100029727 Enteropeptidase Human genes 0.000 description 1
101710091045 Envelope protein Proteins 0.000 description 1
YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 1
241000588698 Erwinia Species 0.000 description 1
241000660147 Escherichia coli str. K-12 substr. MG1655 Species 0.000 description 1
108091029865 Exogenous DNA Proteins 0.000 description 1
101150107205 FCGR2 gene Proteins 0.000 description 1
101150061264 FXR1 gene Proteins 0.000 description 1
208000024720 Fabry Disease Diseases 0.000 description 1
108010074860 Factor Xa Proteins 0.000 description 1
102100036334 Fragile X mental retardation syndrome-related protein 1 Human genes 0.000 description 1
102100036336 Fragile X mental retardation syndrome-related protein 2 Human genes 0.000 description 1
208000001914 Fragile X syndrome Diseases 0.000 description 1
208000002234 Fryns syndrome Diseases 0.000 description 1
201000006813 Fukuyama congenital muscular dystrophy Diseases 0.000 description 1
241000223221 Fusarium oxysporum Species 0.000 description 1
241000611205 Fusarium oxysporum f. sp. lycopersici Species 0.000 description 1
241000605909 Fusobacterium Species 0.000 description 1
208000017462 Galactosialidosis Diseases 0.000 description 1
102100039556 Galectin-4 Human genes 0.000 description 1
102100040004 Gamma-glutamylcyclotransferase Human genes 0.000 description 1
208000015872 Gaucher disease Diseases 0.000 description 1
108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
108700007698 Genetic Terminator Regions Proteins 0.000 description 1
229940123611 Genome editing Drugs 0.000 description 1
208000031448 Genomic Instability Diseases 0.000 description 1
241001135750 Geobacter Species 0.000 description 1
208000003736 Gerstmann-Straussler-Scheinker Disease Diseases 0.000 description 1
206010072075 Gerstmann-Straussler-Scheinker syndrome Diseases 0.000 description 1
208000010055 Globoid Cell Leukodystrophy Diseases 0.000 description 1
108010060309 Glucuronidase Proteins 0.000 description 1
102000053187 Glucuronidase Human genes 0.000 description 1
239000004471 Glycine Substances 0.000 description 1
108010051975 Glycogen Synthase Kinase 3 beta Proteins 0.000 description 1
102100022975 Glycogen synthase kinase-3 alpha Human genes 0.000 description 1
102100038104 Glycogen synthase kinase-3 beta Human genes 0.000 description 1
241000288105 Grus Species 0.000 description 1
102100022662 Guanylyl cyclase C Human genes 0.000 description 1
101710198293 Guanylyl cyclase C Proteins 0.000 description 1
108050008753 HNH endonucleases Proteins 0.000 description 1
102000000310 HNH endonucleases Human genes 0.000 description 1
241000204988 Haloferax mediterranei Species 0.000 description 1
102100021519 Hemoglobin subunit beta Human genes 0.000 description 1
108091005904 Hemoglobin subunit beta Proteins 0.000 description 1
208000036066 Hemophagocytic Lymphohistiocytosis Diseases 0.000 description 1
101001023784 Heteractis crispa GFP-like non-fluorescent chromoprotein Proteins 0.000 description 1
102000016871 Hexosaminidase A Human genes 0.000 description 1
108010053317 Hexosaminidase A Proteins 0.000 description 1
208000032672 Histiocytosis haematophagic Diseases 0.000 description 1
108010033040 Histones Proteins 0.000 description 1
101000761348 Homo sapiens 5-hydroxytryptamine receptor 2C Proteins 0.000 description 1
101100153048 Homo sapiens ACAA1 gene Proteins 0.000 description 1
101000888659 Homo sapiens ARF GTPase-activating protein GIT1 Proteins 0.000 description 1
101000929319 Homo sapiens Actin, aortic smooth muscle Proteins 0.000 description 1
101000783645 Homo sapiens Adenosine receptor A3 Proteins 0.000 description 1
101000775498 Homo sapiens Adenylate cyclase type 10 Proteins 0.000 description 1
101000924552 Homo sapiens Angiopoietin-1 Proteins 0.000 description 1
101000898449 Homo sapiens Cathepsin B Proteins 0.000 description 1
101000761509 Homo sapiens Cathepsin K Proteins 0.000 description 1
101000859600 Homo sapiens Complexin-1 Proteins 0.000 description 1
101000756722 Homo sapiens Disintegrin and metalloproteinase domain-containing protein 22 Proteins 0.000 description 1
101000902072 Homo sapiens Disrupted in schizophrenia 1 protein Proteins 0.000 description 1
101000870166 Homo sapiens DnaJ homolog subfamily C member 14 Proteins 0.000 description 1
101000619542 Homo sapiens E3 ubiquitin-protein ligase parkin Proteins 0.000 description 1
101100335685 Homo sapiens FXR2 gene Proteins 0.000 description 1
101000930945 Homo sapiens Fragile X mental retardation syndrome-related protein 1 Proteins 0.000 description 1
101000930952 Homo sapiens Fragile X mental retardation syndrome-related protein 2 Proteins 0.000 description 1
101000608765 Homo sapiens Galectin-4 Proteins 0.000 description 1
101000886680 Homo sapiens Gamma-glutamylcyclotransferase Proteins 0.000 description 1
101000903717 Homo sapiens Glycogen synthase kinase-3 alpha Proteins 0.000 description 1
101000843809 Homo sapiens Hydroxycarboxylic acid receptor 2 Proteins 0.000 description 1
101000929733 Homo sapiens Kynurenine/alpha-aminoadipate aminotransferase, mitochondrial Proteins 0.000 description 1
101000917826 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-a Proteins 0.000 description 1
101000917824 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-b Proteins 0.000 description 1
101001057159 Homo sapiens Melanoma-associated antigen C3 Proteins 0.000 description 1
101000615488 Homo sapiens Methyl-CpG-binding domain protein 2 Proteins 0.000 description 1
101000829958 Homo sapiens N-acetyllactosaminide beta-1,6-N-acetylglucosaminyl-transferase Proteins 0.000 description 1
101000837517 Homo sapiens NEDD8-activating enzyme E1 catalytic subunit Proteins 0.000 description 1
101001108436 Homo sapiens Neurexin-1 Proteins 0.000 description 1
101001108433 Homo sapiens Neurexin-1-beta Proteins 0.000 description 1
101000974009 Homo sapiens Nitric oxide synthase, brain Proteins 0.000 description 1
101001109698 Homo sapiens Nuclear receptor subfamily 4 group A member 2 Proteins 0.000 description 1
101000617536 Homo sapiens Presenilin-1 Proteins 0.000 description 1
101000617546 Homo sapiens Presenilin-2 Proteins 0.000 description 1
101000845206 Homo sapiens Putative peripheral benzodiazepine receptor-related protein Proteins 0.000 description 1
101000600434 Homo sapiens Putative uncharacterized protein encoded by MIR7-3HG Proteins 0.000 description 1
101100247605 Homo sapiens RCAN1 gene Proteins 0.000 description 1
101000665449 Homo sapiens RNA binding protein fox-1 homolog 1 Proteins 0.000 description 1
101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
101000605835 Homo sapiens Serine/threonine-protein kinase PINK1, mitochondrial Proteins 0.000 description 1
101000845233 Homo sapiens Translocator protein Proteins 0.000 description 1
101000892398 Homo sapiens Tryptophan 2,3-dioxygenase Proteins 0.000 description 1
101000830742 Homo sapiens Tryptophan 5-hydroxylase 1 Proteins 0.000 description 1
101000851865 Homo sapiens Tryptophan 5-hydroxylase 2 Proteins 0.000 description 1
101000867811 Homo sapiens Voltage-dependent L-type calcium channel subunit alpha-1C Proteins 0.000 description 1
101000983956 Homo sapiens Voltage-dependent L-type calcium channel subunit beta-2 Proteins 0.000 description 1
101001074035 Homo sapiens Zinc finger protein GLI2 Proteins 0.000 description 1
206010020460 Human T-cell lymphotropic virus type I infection Diseases 0.000 description 1
241000714260 Human T-lymphotropic virus 1 Species 0.000 description 1
241000701109 Human adenovirus 2 Species 0.000 description 1
208000025500 Hutchinson-Gilford progeria syndrome Diseases 0.000 description 1
102100030643 Hydroxycarboxylic acid receptor 2 Human genes 0.000 description 1
108010073807 IgG Receptors Proteins 0.000 description 1
102000009490 IgG Receptors Human genes 0.000 description 1
206010061598 Immunodeficiency Diseases 0.000 description 1
208000029462 Immunodeficiency disease Diseases 0.000 description 1
108060003951 Immunoglobulin Proteins 0.000 description 1
208000028547 Inborn Urea Cycle disease Diseases 0.000 description 1
102000000589 Interleukin-1 Human genes 0.000 description 1
108010002352 Interleukin-1 Proteins 0.000 description 1
208000021548 Jervell and Lange-Nielsen syndrome Diseases 0.000 description 1
201000003992 Jervell-Lange Nielsen Syndrome Diseases 0.000 description 1
208000028226 Krabbe disease Diseases 0.000 description 1
208000012383 LAMA2-related muscular dystrophy Diseases 0.000 description 1
208000031905 Laminin subunit alpha 2-related muscular dystrophy Diseases 0.000 description 1
102100022745 Laminin subunit alpha-2 Human genes 0.000 description 1
241000589248 Legionella Species 0.000 description 1
208000007764 Legionnaires' Disease Diseases 0.000 description 1
208000006136 Leigh Disease Diseases 0.000 description 1
208000017507 Leigh syndrome Diseases 0.000 description 1
108010020246 Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 Proteins 0.000 description 1
102100032693 Leucine-rich repeat serine/threonine-protein kinase 2 Human genes 0.000 description 1
102000003960 Ligases Human genes 0.000 description 1
108090000364 Ligases Proteins 0.000 description 1
206010048911 Lissencephaly Diseases 0.000 description 1
241000186781 Listeria Species 0.000 description 1
206010057926 Long QT syndrome congenital Diseases 0.000 description 1
102100029204 Low affinity immunoglobulin gamma Fc region receptor II-a Human genes 0.000 description 1
108060001084 Luciferase Proteins 0.000 description 1
239000005089 Luciferase Substances 0.000 description 1
239000006142 Luria-Bertani Agar Substances 0.000 description 1
208000003221 Lysosomal acid lipase deficiency Diseases 0.000 description 1
102100033448 Lysosomal alpha-glucosidase Human genes 0.000 description 1
208000024889 MECP2 duplication syndrome Diseases 0.000 description 1
239000007993 MOPS buffer Substances 0.000 description 1
GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
208000030162 Maple syrup disease Diseases 0.000 description 1
108010049137 Member 1 Subfamily D ATP Binding Cassette Transporter Proteins 0.000 description 1
108010090822 Member 8 Subfamily G ATP Binding Cassette Transporter Proteins 0.000 description 1
241001214257 Mene Species 0.000 description 1
208000008948 Menkes Kinky Hair Syndrome Diseases 0.000 description 1
208000012583 Menkes disease Diseases 0.000 description 1
201000011442 Metachromatic leukodystrophy Diseases 0.000 description 1
241000202974 Methanobacterium Species 0.000 description 1
241000203353 Methanococcus Species 0.000 description 1
241000205276 Methanosarcina Species 0.000 description 1
102000006890 Methyl-CpG-Binding Protein 2 Human genes 0.000 description 1
108010072388 Methyl-CpG-Binding Protein 2 Proteins 0.000 description 1
102100021299 Methyl-CpG-binding domain protein 2 Human genes 0.000 description 1
241000589345 Methylococcus Species 0.000 description 1
206010051403 Mitochondrial DNA deletion Diseases 0.000 description 1
208000035155 Mitochondrial DNA-associated Leigh syndrome Diseases 0.000 description 1
201000002169 Mitochondrial myopathy Diseases 0.000 description 1
208000034819 Mobility Limitation Diseases 0.000 description 1
208000033180 Monosomy 22q13.3 Diseases 0.000 description 1
241000993286 Mucidula mucida Species 0.000 description 1
208000008955 Mucolipidoses Diseases 0.000 description 1
206010072927 Mucolipidosis type I Diseases 0.000 description 1
206010072928 Mucolipidosis type II Diseases 0.000 description 1
208000002678 Mucopolysaccharidoses Diseases 0.000 description 1
102000016943 Muramidase Human genes 0.000 description 1
108010014251 Muramidase Proteins 0.000 description 1
101100144701 Mus musculus Drosha gene Proteins 0.000 description 1
101000981253 Mus musculus GPI-linked NAD(P)(+)-arginine ADP-ribosyltransferase 1 Proteins 0.000 description 1
208000007101 Muscle Cramp Diseases 0.000 description 1
102100038895 Myc proto-oncogene protein Human genes 0.000 description 1
101710135898 Myc proto-oncogene protein Proteins 0.000 description 1
241000186359 Mycobacterium Species 0.000 description 1
241000187479 Mycobacterium tuberculosis Species 0.000 description 1
241000204031 Mycoplasma Species 0.000 description 1
208000036572 Myoclonic epilepsy Diseases 0.000 description 1
108010062374 Myoglobin Proteins 0.000 description 1
201000004458 Myoma Diseases 0.000 description 1
241000863420 Myxococcus Species 0.000 description 1
108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
102100023315 N-acetyllactosaminide beta-1,6-N-acetylglucosaminyl-transferase Human genes 0.000 description 1
108700037255 NEDD8-activating enzyme E1 catalytic subunit Proteins 0.000 description 1
108010054200 NR2B NMDA receptor Proteins 0.000 description 1
108091061960 Naked DNA Proteins 0.000 description 1
241000588653 Neisseria Species 0.000 description 1
208000009869 Neu-Laxova syndrome Diseases 0.000 description 1
102000048238 Neuregulin-1 Human genes 0.000 description 1
108090000556 Neuregulin-1 Proteins 0.000 description 1
102100021582 Neurexin-1-beta Human genes 0.000 description 1
108010088373 Neurofilament Proteins Proteins 0.000 description 1
102000008763 Neurofilament Proteins Human genes 0.000 description 1
101100058191 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) bcp-1 gene Proteins 0.000 description 1
101100385413 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) csm-3 gene Proteins 0.000 description 1
208000010577 Niemann-Pick disease type C Diseases 0.000 description 1
108010008858 Nitric Oxide Synthase Type I Proteins 0.000 description 1
108091092724 Noncoding DNA Proteins 0.000 description 1
208000035544 Nonketotic hyperglycinaemia Diseases 0.000 description 1
102100022676 Nuclear receptor subfamily 4 group A member 2 Human genes 0.000 description 1
208000035023 Oculocerebrorenal syndrome of Lowe Diseases 0.000 description 1
108700026244 Open Reading Frames Proteins 0.000 description 1
206010031243 Osteogenesis imperfecta Diseases 0.000 description 1
208000018344 PLA2G6-associated neurodegeneration Diseases 0.000 description 1
108010011536 PTEN Phosphohydrolase Proteins 0.000 description 1
241000606860 Pasteurella Species 0.000 description 1
241001494479 Pecora Species 0.000 description 1
241000009328 Perro Species 0.000 description 1
201000004316 Perry syndrome Diseases 0.000 description 1
201000006880 Phelan-McDermid syndrome Diseases 0.000 description 1
102100032543 Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN Human genes 0.000 description 1
241000607568 Photobacterium Species 0.000 description 1
ZYFVNVRFVHJEIU-UHFFFAOYSA-N PicoGreen Chemical compound CN(C)CCCN(CCCN(C)C)C1=CC(=CC2=[N+](C3=CC=CC=C3S2)C)C2=CC=CC=C2N1C1=CC=CC=C1 ZYFVNVRFVHJEIU-UHFFFAOYSA-N 0.000 description 1
241000204826 Picrophilus Species 0.000 description 1
102000012338 Poly(ADP-ribose) Polymerases Human genes 0.000 description 1
108010061844 Poly(ADP-ribose) Polymerases Proteins 0.000 description 1
229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 description 1
108010036933 Presenilin-1 Proteins 0.000 description 1
108010036908 Presenilin-2 Proteins 0.000 description 1
208000007932 Progeria Diseases 0.000 description 1
208000033063 Progressive myoclonic epilepsy Diseases 0.000 description 1
229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
102000007659 Protein Deglycase DJ-1 Human genes 0.000 description 1
108010032428 Protein Deglycase DJ-1 Proteins 0.000 description 1
108010029485 Protein Isoforms Proteins 0.000 description 1
102000001708 Protein Isoforms Human genes 0.000 description 1
101710188315 Protein X Proteins 0.000 description 1
101710130181 Protochlorophyllide reductase A, chloroplastic Proteins 0.000 description 1
101710138718 Protochlorophyllide reductase B, chloroplastic Proteins 0.000 description 1
208000033876 Proximal Xq28 duplication syndrome Diseases 0.000 description 1
101100396930 Pseudomonas aeruginosa imm1 gene Proteins 0.000 description 1
241000567197 Puccinia graminis f. sp. tritici Species 0.000 description 1
102100031269 Putative peripheral benzodiazepine receptor-related protein Human genes 0.000 description 1
102100037401 Putative uncharacterized protein encoded by MIR7-3HG Human genes 0.000 description 1
241000205226 Pyrobaculum Species 0.000 description 1
241000205160 Pyrococcus Species 0.000 description 1
102000014450 RNA Polymerase III Human genes 0.000 description 1
108010078067 RNA Polymerase III Proteins 0.000 description 1
101710199540 RNA binding protein fox-1 homolog 1 Proteins 0.000 description 1
230000007022 RNA scission Effects 0.000 description 1
101100240886 Rattus norvegicus Nptx2 gene Proteins 0.000 description 1
101100047461 Rattus norvegicus Trpm8 gene Proteins 0.000 description 1
102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 1
101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 description 1
102100029986 Receptor tyrosine-protein kinase erbB-3 Human genes 0.000 description 1
102100029981 Receptor tyrosine-protein kinase erbB-4 Human genes 0.000 description 1
101710100963 Receptor tyrosine-protein kinase erbB-4 Proteins 0.000 description 1
102100033617 Retinal-specific phospholipid-transporting ATPase ABCA4 Human genes 0.000 description 1
201000000582 Retinoblastoma Diseases 0.000 description 1
201000008539 Rhizomelic chondrodysplasia punctata type 1 Diseases 0.000 description 1
108010083644 Ribonucleases Proteins 0.000 description 1
102000006382 Ribonucleases Human genes 0.000 description 1
108091028664 Ribonucleotide Proteins 0.000 description 1
201000001718 Roberts syndrome Diseases 0.000 description 1
101100170553 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) DLD2 gene Proteins 0.000 description 1
241000607142 Salmonella Species 0.000 description 1
208000021811 Sandhoff disease Diseases 0.000 description 1
101100023124 Schizosaccharomyces pombe (strain 972 / ATCC 24843) mfr2 gene Proteins 0.000 description 1
101100395426 Schizosaccharomyces pombe (strain 972 / ATCC 24843) sty1 gene Proteins 0.000 description 1
101150068315 Scn2a gene Proteins 0.000 description 1
108091081021 Sense strand Proteins 0.000 description 1
102100038376 Serine/threonine-protein kinase PINK1, mitochondrial Human genes 0.000 description 1
102220520989 Serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha_K42T_mutation Human genes 0.000 description 1
206010073677 Severe myoclonic epilepsy of infancy Diseases 0.000 description 1
201000007410 Smith-Lemli-Opitz syndrome Diseases 0.000 description 1
208000005392 Spasm Diseases 0.000 description 1
241000191940 Staphylococcus Species 0.000 description 1
108091081024 Start codon Proteins 0.000 description 1
102100036325 Sterol 26-hydroxylase, mitochondrial Human genes 0.000 description 1
201000005010 Streptococcus pneumonia Diseases 0.000 description 1
241000187747 Streptomyces Species 0.000 description 1
102100021997 Synphilin-1 Human genes 0.000 description 1
101710140334 Synphilin-1 Proteins 0.000 description 1
108700005078 Synthetic Genes Proteins 0.000 description 1
239000012163 TRI reagent Substances 0.000 description 1
241000255588 Tephritidae Species 0.000 description 1
241000186339 Thermoanaerobacter Species 0.000 description 1
241000204667 Thermoplasma Species 0.000 description 1
241000204652 Thermotoga Species 0.000 description 1
241000589596 Thermus Species 0.000 description 1
229910052776 Thorium Inorganic materials 0.000 description 1
108010022394 Threonine synthase Proteins 0.000 description 1
108090000190 Thrombin Proteins 0.000 description 1
241000283907 Tragelaphus oryx Species 0.000 description 1
108700009124 Transcription Initiation Site Proteins 0.000 description 1
101710150448 Transcriptional regulator Myc Proteins 0.000 description 1
241000589886 Treponema Species 0.000 description 1
239000007983 Tris buffer Substances 0.000 description 1
241000209140 Triticum Species 0.000 description 1
235000021307 Triticum Nutrition 0.000 description 1
229920004890 Triton X-100 Polymers 0.000 description 1
239000013504 Triton X-100 Substances 0.000 description 1
102100040653 Tryptophan 2,3-dioxygenase Human genes 0.000 description 1
102100024971 Tryptophan 5-hydroxylase 1 Human genes 0.000 description 1
208000007930 Type C Niemann-Pick Disease Diseases 0.000 description 1
108091026822 U6 spliceosomal RNA Proteins 0.000 description 1
101150044377 UBA1 gene Proteins 0.000 description 1
101150035006 UBA3 gene Proteins 0.000 description 1
108010005656 Ubiquitin Thiolesterase Proteins 0.000 description 1
102000005918 Ubiquitin Thiolesterase Human genes 0.000 description 1
208000014769 Usher Syndromes Diseases 0.000 description 1
241000251539 Vertebrata <Metazoa> Species 0.000 description 1
101710177612 Very low-density lipoprotein receptor Proteins 0.000 description 1
108020005202 Viral DNA Proteins 0.000 description 1
101150115477 Vldlr gene Proteins 0.000 description 1
102100025807 Voltage-dependent L-type calcium channel subunit beta-2 Human genes 0.000 description 1
201000006793 Walker-Warburg syndrome Diseases 0.000 description 1
239000005862 Whey Substances 0.000 description 1
102000007544 Whey Proteins Human genes 0.000 description 1
108010046377 Whey Proteins Proteins 0.000 description 1
208000006254 Wolf-Hirschhorn Syndrome Diseases 0.000 description 1
241000605941 Wolinella Species 0.000 description 1
241001492404 Woodchuck hepatitis virus Species 0.000 description 1
101000678336 Xenopus laevis Actin, alpha skeletal muscle 2 Proteins 0.000 description 1
101000678338 Xenopus tropicalis Actin, alpha cardiac muscle 2 Proteins 0.000 description 1
201000006083 Xeroderma Pigmentosum Diseases 0.000 description 1
241000607734 Yersinia <bacteria> Species 0.000 description 1
102100035558 Zinc finger protein GLI2 Human genes 0.000 description 1
WCDYMMVGBZNUGB-ORPFKJIMSA-N [(2r,3r,4s,5r,6r)-6-[[(1r,3r,4r,5r,6r)-4,5-dihydroxy-2,7-dioxabicyclo[4.2.0]octan-3-yl]oxy]-3,4,5-trihydroxyoxan-2-yl]methyl 3-hydroxy-2-tetradecyloctadecanoate Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](COC(=O)C(CCCCCCCCCCCCCC)C(O)CCCCCCCCCCCCCCC)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H]2OC[C@H]2O1 WCDYMMVGBZNUGB-ORPFKJIMSA-N 0.000 description 1
230000005856 abnormality Effects 0.000 description 1
230000021736 acetylation Effects 0.000 description 1
238000006640 acetylation reaction Methods 0.000 description 1
230000003213 activating effect Effects 0.000 description 1
201000009628 adenosine deaminase deficiency Diseases 0.000 description 1
230000002411 adverse Effects 0.000 description 1
238000001261 affinity purification Methods 0.000 description 1
206010064930 age-related macular degeneration Diseases 0.000 description 1
230000009418 agronomic effect Effects 0.000 description 1
235000004279 alanine Nutrition 0.000 description 1
125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 1
108010029483 alpha 1 Chain Collagen Type I Proteins 0.000 description 1
102000009899 alpha Karyopherins Human genes 0.000 description 1
108010077099 alpha Karyopherins Proteins 0.000 description 1
108020004102 alpha-1 Adrenergic Receptor Proteins 0.000 description 1
108010026331 alpha-Fetoproteins Proteins 0.000 description 1
201000008333 alpha-mannosidosis Diseases 0.000 description 1
125000000539 amino acid group Chemical group 0.000 description 1
108010025592 aminoadipoyl-cysteinyl-allylglycine Proteins 0.000 description 1
238000000540 analysis of variance Methods 0.000 description 1
230000019552 anatomical structure morphogenesis Effects 0.000 description 1
230000003466 anti-cipated effect Effects 0.000 description 1
239000000427 antigen Substances 0.000 description 1
108091007433 antigens Proteins 0.000 description 1
102000036639 antigens Human genes 0.000 description 1
239000003293 antisense oligodeoxyribonucleotide Substances 0.000 description 1
210000000709 aorta Anatomy 0.000 description 1
235000009697 arginine Nutrition 0.000 description 1
150000001484 arginines Chemical class 0.000 description 1
238000003149 assay kit Methods 0.000 description 1
230000005784 autoimmunity Effects 0.000 description 1
208000036556 autosomal recessive T cell-negative B cell-negative NK cell-negative due to adenosine deaminase deficiency severe combined immunodeficiency Diseases 0.000 description 1
210000003578 bacterial chromosome Anatomy 0.000 description 1
230000008970 bacterial immunity Effects 0.000 description 1
208000022362 bacterial infectious disease Diseases 0.000 description 1
230000037429 base substitution Effects 0.000 description 1
208000005980 beta thalassemia Diseases 0.000 description 1
108091008324 binding proteins Proteins 0.000 description 1
230000008236 biological pathway Effects 0.000 description 1
238000001369 bisulfite sequencing Methods 0.000 description 1
238000006664 bond formation reaction Methods 0.000 description 1
210000000988 bone and bone Anatomy 0.000 description 1
229940041514 candida albicans extract Drugs 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
125000002091 cationic group Chemical group 0.000 description 1
230000001364 causal effect Effects 0.000 description 1
230000022131 cell cycle Effects 0.000 description 1
230000032823 cell division Effects 0.000 description 1
239000013592 cell lysate Substances 0.000 description 1
208000025434 cerebellar degeneration Diseases 0.000 description 1
208000016886 cerebral arteriopathy with subcortical infarcts and leukoencephalopathy Diseases 0.000 description 1
210000003710 cerebral cortex Anatomy 0.000 description 1
208000001088 cerebrotendinous xanthomatosis Diseases 0.000 description 1
238000012512 characterization method Methods 0.000 description 1
210000003763 chloroplast Anatomy 0.000 description 1
208000035110 classic form autosomal dominant optic atrophy Diseases 0.000 description 1
229920001436 collagen Polymers 0.000 description 1
208000003536 colpocephaly Diseases 0.000 description 1
238000002742 combinatorial mutagenesis Methods 0.000 description 1
230000009850 completed effect Effects 0.000 description 1
239000012141 concentrate Substances 0.000 description 1
235000008504 concentrate Nutrition 0.000 description 1
201000006815 congenital muscular dystrophy Diseases 0.000 description 1
238000011109 contamination Methods 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
210000000877 corpus callosum Anatomy 0.000 description 1
239000013078 crystal Substances 0.000 description 1
101150064416 csp1 gene Proteins 0.000 description 1
238000012258 culturing Methods 0.000 description 1
210000000805 cytoplasm Anatomy 0.000 description 1
SPTYHKZRPFATHJ-HYZXJONISA-N dT6 Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(=O)O[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)O[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)O[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)O[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)O[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)CO)[C@@H](O)C1 SPTYHKZRPFATHJ-HYZXJONISA-N 0.000 description 1
238000007405 data analysis Methods 0.000 description 1
230000007812 deficiency Effects 0.000 description 1
238000006731 degradation reaction Methods 0.000 description 1
239000005547 deoxyribonucleotide Substances 0.000 description 1
125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
238000011161 development Methods 0.000 description 1
230000018109 developmental process Effects 0.000 description 1
238000003745 diagnosis Methods 0.000 description 1
102000004419 dihydrofolate reductase Human genes 0.000 description 1
230000005750 disease progression Effects 0.000 description 1
206010013663 drug dependence Diseases 0.000 description 1
238000007877 drug screening Methods 0.000 description 1
241001493065 dsRNA viruses Species 0.000 description 1
230000008190 early vertebrate development Effects 0.000 description 1
208000025688 early-onset autosomal dominant Alzheimer disease Diseases 0.000 description 1
230000013020 embryo development Effects 0.000 description 1
230000002708 enhancing effect Effects 0.000 description 1
238000001952 enzyme assay Methods 0.000 description 1
230000007717 exclusion Effects 0.000 description 1
239000013613 expression plasmid Substances 0.000 description 1
208000015756 familial Alzheimer disease Diseases 0.000 description 1
230000001605 fetal effect Effects 0.000 description 1
238000002795 fluorescence method Methods 0.000 description 1
108010021843 fluorescent protein 583 Proteins 0.000 description 1
231100000221 frame shift mutation induction Toxicity 0.000 description 1
201000008049 fucosidosis Diseases 0.000 description 1
101150045500 galK gene Proteins 0.000 description 1
238000001476 gene delivery Methods 0.000 description 1
238000007429 general method Methods 0.000 description 1
239000003862 glucocorticoid Substances 0.000 description 1
201000011205 glycine encephalopathy Diseases 0.000 description 1
230000013595 glycosylation Effects 0.000 description 1
238000006206 glycosylation reaction Methods 0.000 description 1
PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
208000014752 hemophagocytic syndrome Diseases 0.000 description 1
208000006454 hepatitis Diseases 0.000 description 1
231100000283 hepatitis Toxicity 0.000 description 1
HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
210000005119 human aortic smooth muscle cell Anatomy 0.000 description 1
210000005260 human cell Anatomy 0.000 description 1
239000005457 ice water Substances 0.000 description 1
230000008076 immune mechanism Effects 0.000 description 1
230000007813 immunodeficiency Effects 0.000 description 1
102000018358 immunoglobulin Human genes 0.000 description 1
229940072221 immunoglobulins Drugs 0.000 description 1
238000003364 immunohistochemistry Methods 0.000 description 1
230000008676 import Effects 0.000 description 1
238000000126 in silico method Methods 0.000 description 1
208000010194 infantile onset spinocerebellar ataxia Diseases 0.000 description 1
208000015181 infectious disease Diseases 0.000 description 1
206010022000 influenza Diseases 0.000 description 1
108700032552 influenza virus INS1 Proteins 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
230000009878 intermolecular interaction Effects 0.000 description 1
208000008106 junctional epidermolysis bullosa Diseases 0.000 description 1
208000017476 juvenile neuronal ceroid lipofuscinosis Diseases 0.000 description 1
101150044508 key gene Proteins 0.000 description 1
238000011813 knockout mouse model Methods 0.000 description 1
238000011005 laboratory method Methods 0.000 description 1
238000012177 large-scale sequencing Methods 0.000 description 1
239000003446 ligand Substances 0.000 description 1
230000029226 lipidation Effects 0.000 description 1
208000014817 lissencephaly spectrum disease Diseases 0.000 description 1
239000012160 loading buffer Substances 0.000 description 1
230000007774 longterm Effects 0.000 description 1
210000004698 lymphocyte Anatomy 0.000 description 1
235000018977 lysine Nutrition 0.000 description 1
150000002669 lysines Chemical class 0.000 description 1
239000012139 lysis buffer Substances 0.000 description 1
229960000274 lysozyme Drugs 0.000 description 1
239000004325 lysozyme Substances 0.000 description 1
235000010335 lysozyme Nutrition 0.000 description 1
210000000415 mammalian chromosome Anatomy 0.000 description 1
210000001161 mammalian embryo Anatomy 0.000 description 1
210000005075 mammary gland Anatomy 0.000 description 1
208000024393 maple syrup urine disease Diseases 0.000 description 1
239000000463 material Substances 0.000 description 1
238000005259 measurement Methods 0.000 description 1
230000010534 mechanism of action Effects 0.000 description 1
230000000813 microbial effect Effects 0.000 description 1
244000005700 microbiome Species 0.000 description 1
238000000520 microinjection Methods 0.000 description 1
235000013336 milk Nutrition 0.000 description 1
239000008267 milk Substances 0.000 description 1
210000004080 milk Anatomy 0.000 description 1
230000003278 mimic effect Effects 0.000 description 1
210000003470 mitochondria Anatomy 0.000 description 1
201000011561 mitochondrial DNA depletion syndrome 7 Diseases 0.000 description 1
230000009456 molecular mechanism Effects 0.000 description 1
208000020460 mucolipidosis II alpha/beta Diseases 0.000 description 1
206010028093 mucopolysaccharidosis Diseases 0.000 description 1
101150034514 murC gene Proteins 0.000 description 1
210000003205 muscle Anatomy 0.000 description 1
208000025855 muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 Diseases 0.000 description 1
CJWXCNXHAIFFMH-AVZHFPDBSA-N n-[(2s,3r,4s,5s,6r)-2-[(2r,3r,4s,5r)-2-acetamido-4,5,6-trihydroxy-1-oxohexan-3-yl]oxy-3,5-dihydroxy-6-methyloxan-4-yl]acetamide Chemical compound C[C@H]1O[C@@H](O[C@@H]([C@@H](O)[C@H](O)CO)[C@@H](NC(C)=O)C=O)[C@H](O)[C@@H](NC(C)=O)[C@@H]1O CJWXCNXHAIFFMH-AVZHFPDBSA-N 0.000 description 1
208000033510 neuroaxonal dystrophy Diseases 0.000 description 1
201000007601 neurodegeneration with brain iron accumulation Diseases 0.000 description 1
230000000626 neurodegenerative effect Effects 0.000 description 1
230000001123 neurodevelopmental effect Effects 0.000 description 1
210000005044 neurofilament Anatomy 0.000 description 1
201000007607 neuronal ceroid lipofuscinosis 3 Diseases 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
201000006352 oculocerebrorenal syndrome Diseases 0.000 description 1
229940046166 oligodeoxynucleotide Drugs 0.000 description 1
208000001749 optic atrophy Diseases 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
210000003463 organelle Anatomy 0.000 description 1
201000008152 organic acidemia Diseases 0.000 description 1
230000008520 organization Effects 0.000 description 1
102000045222 parkin Human genes 0.000 description 1
238000005192 partition Methods 0.000 description 1
239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
238000010647 peptide synthesis reaction Methods 0.000 description 1
239000000816 peptidomimetic Substances 0.000 description 1
208000023269 peroxisome biogenesis disease Diseases 0.000 description 1
238000003976 plant breeding Methods 0.000 description 1
230000008488 polyadenylation Effects 0.000 description 1
238000006116 polymerization reaction Methods 0.000 description 1
230000001124 posttranscriptional effect Effects 0.000 description 1
HIGSLXSBYYMVKI-UHFFFAOYSA-N pralidoxime chloride Chemical compound [Cl-].C[N+]1=CC=CC=C1\C=N\O HIGSLXSBYYMVKI-UHFFFAOYSA-N 0.000 description 1
238000003825 pressing Methods 0.000 description 1
230000037452 priming Effects 0.000 description 1
238000004393 prognosis Methods 0.000 description 1
230000000750 progressive effect Effects 0.000 description 1
201000001204 progressive myoclonus epilepsy Diseases 0.000 description 1
230000000644 propagated effect Effects 0.000 description 1
210000002307 prostate Anatomy 0.000 description 1
239000012474 protein marker Substances 0.000 description 1
230000012743 protein tagging Effects 0.000 description 1
230000006337 proteolytic cleavage Effects 0.000 description 1
239000012264 purified product Substances 0.000 description 1
239000002096 quantum dot Substances 0.000 description 1
102000005962 receptors Human genes 0.000 description 1
108020003175 receptors Proteins 0.000 description 1
238000009877 rendering Methods 0.000 description 1
230000008263 repair mechanism Effects 0.000 description 1
230000029058 respiratory gaseous exchange Effects 0.000 description 1
108091008146 restriction endonucleases Proteins 0.000 description 1
238000012552 review Methods 0.000 description 1
239000002336 ribonucleotide Substances 0.000 description 1
125000002652 ribonucleotide group Chemical group 0.000 description 1
108020004418 ribosomal RNA Proteins 0.000 description 1
210000003705 ribosome Anatomy 0.000 description 1
108091092562 ribozyme Proteins 0.000 description 1
238000005070 sampling Methods 0.000 description 1
238000012216 screening Methods 0.000 description 1
238000000926 separation method Methods 0.000 description 1
238000012772 sequence design Methods 0.000 description 1
238000013207 serial dilution Methods 0.000 description 1
230000035939 shock Effects 0.000 description 1
230000005783 single-strand break Effects 0.000 description 1
238000002741 site-directed mutagenesis Methods 0.000 description 1
210000003491 skin Anatomy 0.000 description 1
239000002002 slurry Substances 0.000 description 1
210000002460 smooth muscle Anatomy 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
108090000250 sortase A Proteins 0.000 description 1
208000002320 spinal muscular atrophy Diseases 0.000 description 1
230000006641 stabilisation Effects 0.000 description 1
238000011105 stabilization Methods 0.000 description 1
238000007619 statistical method Methods 0.000 description 1
238000013179 statistical model Methods 0.000 description 1
108020003113 steroid hormone receptors Proteins 0.000 description 1
102000005969 steroid hormone receptors Human genes 0.000 description 1
238000003860 storage Methods 0.000 description 1
208000011117 substance-related disease Diseases 0.000 description 1
239000000758 substrate Substances 0.000 description 1
239000013589 supplement Substances 0.000 description 1
230000005062 synaptic transmission Effects 0.000 description 1
238000010809 targeting technique Methods 0.000 description 1
230000002123 temporal effect Effects 0.000 description 1
208000016094 thanatophoric dysplasia type 1 Diseases 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
229940094937 thioredoxin Drugs 0.000 description 1
229960004072 thrombin Drugs 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
230000005029 transcription elongation Effects 0.000 description 1
238000000844 transformation Methods 0.000 description 1
238000011426 transformation method Methods 0.000 description 1
230000001131 transforming effect Effects 0.000 description 1
208000037918 transfusion-transmitted disease Diseases 0.000 description 1
230000010474 transient expression Effects 0.000 description 1
238000003146 transient transfection Methods 0.000 description 1
230000032258 transport Effects 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
230000010415 tropism Effects 0.000 description 1
230000005760 tumorsuppression Effects 0.000 description 1
229910052721 tungsten Inorganic materials 0.000 description 1
208000030954 urea cycle disease Diseases 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
210000003501 vero cell Anatomy 0.000 description 1
210000002845 virion Anatomy 0.000 description 1
239000000277 virosome Substances 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
238000001262 western blot Methods 0.000 description 1
239000012130 whole-cell lysate Substances 0.000 description 1
210000005253 yeast cell Anatomy 0.000 description 1
239000012138 yeast extract Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
- C12N15/90—Stable introduction of foreign DNA into chromosome
- C12N15/902—Stable introduction of foreign DNA into chromosome using homologous recombination
- C12N15/907—Stable introduction of foreign DNA into chromosome using homologous recombination in mammalian cells
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
- C12N9/22—Ribonucleases [RNase]; Deoxyribonucleases [DNase]

Landscapes

Health & Medical Sciences (AREA)
Genetics & Genomics (AREA)
Life Sciences & Earth Sciences (AREA)
Engineering & Computer Science (AREA)
Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Wood Science & Technology (AREA)
Organic Chemistry (AREA)
Biomedical Technology (AREA)
Zoology (AREA)
Biotechnology (AREA)
General Engineering & Computer Science (AREA)
Molecular Biology (AREA)
Microbiology (AREA)
Biochemistry (AREA)
General Health & Medical Sciences (AREA)
Physics & Mathematics (AREA)
Plant Pathology (AREA)
Biophysics (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Cell Biology (AREA)
Mycology (AREA)
Micro-Organisms Or Cultivation Processes Thereof (AREA)
Enzymes And Modification Thereof (AREA)

DK13812430.0T 2012-12-12 2013-12-12 SYSTEMS, PROCEDURES, AND COMPOSITIONS WITH CRISPR-CAS COMPONENTS FOR SEQUENCE MANIPULATION. DK2825654T3 (en)

Applications Claiming Priority (7)

Application Number	Priority Date	Filing Date	Title
US201261736527P	2012-12-12	2012-12-12
US201361748427P	2013-01-02	2013-01-02
US201361757972P	2013-01-29	2013-01-29
US201361768959P	2013-02-25	2013-02-25
US201361791409P	2013-03-15	2013-03-15
US201361835931P	2013-06-17	2013-06-17
PCT/US2013/074611 WO2014093595A1 (en)	2012-12-12	2013-12-12	Crispr-cas component systems, methods and compositions for sequence manipulation

Publications (1)

Publication Number	Publication Date
DK2825654T3 true DK2825654T3 (en)	2017-08-21

Family

ID=55306645

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DK13812430.0T DK2825654T3 (en)	2012-12-12	2013-12-12	SYSTEMS, PROCEDURES, AND COMPOSITIONS WITH CRISPR-CAS COMPONENTS FOR SEQUENCE MANIPULATION.

Country Status (3)

Country	Link
DK (1)	DK2825654T3 (es)
ES (3)	ES2861623T3 (es)
RU (1)	RU2701662C9 (es)

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US9534224B2 (en) *	2002-11-15	2017-01-03	Trustees Of Boston University	Cis/trans riboregulators
DK2341149T3 (en) *	2005-08-26	2017-02-27	Dupont Nutrition Biosci Aps	Use of CRISPR-associated genes (Cas)
US20100076057A1 (en) *	2008-09-23	2010-03-25	Northwestern University	TARGET DNA INTERFERENCE WITH crRNA
WO2012164565A1 (en) *	2011-06-01	2012-12-06	Yeda Research And Development Co. Ltd.	Compositions and methods for downregulating prokaryotic genes

2013
- 2013-12-12 ES ES17162030T patent/ES2861623T3/es active Active
- 2013-12-12 DK DK13812430.0T patent/DK2825654T3/en active
- 2013-12-12 ES ES13812430.0T patent/ES2635244T3/es active Active
- 2013-12-12 ES ES14188820.6T patent/ES2618531T3/es active Active
- 2013-12-12 RU RU2015128102A patent/RU2701662C9/ru active

Also Published As

Publication number	Publication date
RU2015128102A (ru)	2018-12-21
RU2701662C9 (ru)	2019-10-31
HK1208045A1 (en)	2016-02-19
ES2861623T3 (es)	2021-10-06
ES2635244T3 (es)	2017-10-03
ES2618531T3 (es)	2017-06-21
HK1247961A1 (en)	2018-10-05
RU2701662C2 (ru)	2019-09-30
RU2019127238A (ru)	2019-09-20
RU2015128102A3 (es)	2018-12-21

Publication	Publication Date	Title
JP7542681B2 (ja)	2024-08-30	配列操作のためのＣＲＩＳＰＲ－Ｃａｓ成分系、方法および組成物
JP7542595B2 (ja)	2024-08-30	配列操作のための系、方法および最適化ガイド組成物のエンジニアリング
JP7463436B2 (ja)	2024-04-08	遺伝子産物の発現を変更するためのＣＲＩＳＰＲ－Ｃａｓ系および方法
DK2921557T3 (en)	2016-11-07	Design of systems, methods and optimized sequence manipulation guide compositions
DK2898075T3 (en)	2016-06-27	CONSTRUCTION AND OPTIMIZATION OF IMPROVED SYSTEMS, PROCEDURES AND ENZYME COMPOSITIONS FOR SEQUENCE MANIPULATION
WO2014093694A1 (en)	2014-06-19	Crispr-cas nickase systems, methods and compositions for sequence manipulation in eukaryotes
DK2825654T3 (en)	2017-08-21	SYSTEMS, PROCEDURES, AND COMPOSITIONS WITH CRISPR-CAS COMPONENTS FOR SEQUENCE MANIPULATION.
HK1216759B (zh)	2022-01-21	用於序列操纵的系统、方法和优化的指导组合物的工程化