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SG10201912907PA - Gene editing of deep intronic mutations - Google Patents

Gene editing of deep intronic mutations

Info

Publication number
SG10201912907PA
SG10201912907PA SG10201912907PA SG10201912907PA SG10201912907PA SG 10201912907P A SG10201912907P A SG 10201912907PA SG 10201912907P A SG10201912907P A SG 10201912907PA SG 10201912907P A SG10201912907P A SG 10201912907PA SG 10201912907P A SG10201912907P A SG 10201912907PA
Authority
SG
Singapore
Prior art keywords
gene editing
deep intronic
intronic mutations
mutations
deep
Prior art date
Application number
SG10201912907PA
Inventor
Guoxiang Ruan
Abraham Scaria
Original Assignee
Genzyme Corp
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.)
Filing date
Publication date
Application filed by Genzyme Corp filed Critical Genzyme Corp
Publication of SG10201912907PA publication Critical patent/SG10201912907PA/en

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SG10201912907PA 2015-05-16 2016-04-15 Gene editing of deep intronic mutations SG10201912907PA (en)

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JP (3) JP6985250B2 (en)
KR (2) KR20230142649A (en)
CN (3) CN118879692A (en)
AU (2) AU2016265255B2 (en)
BR (1) BR112017024514A2 (en)
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Families Citing this family (76)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2734621B1 (en) 2011-07-22 2019-09-04 President and Fellows of Harvard College Evaluation and improvement of nuclease cleavage specificity
US20150044192A1 (en) 2013-08-09 2015-02-12 President And Fellows Of Harvard College Methods for identifying a target site of a cas9 nuclease
US9359599B2 (en) 2013-08-22 2016-06-07 President And Fellows Of Harvard College Engineered transcription activator-like effector (TALE) domains and uses thereof
US9340800B2 (en) 2013-09-06 2016-05-17 President And Fellows Of Harvard College Extended DNA-sensing GRNAS
US9526784B2 (en) 2013-09-06 2016-12-27 President And Fellows Of Harvard College Delivery system for functional nucleases
US9388430B2 (en) 2013-09-06 2016-07-12 President And Fellows Of Harvard College Cas9-recombinase fusion proteins and uses thereof
US9840699B2 (en) 2013-12-12 2017-12-12 President And Fellows Of Harvard College Methods for nucleic acid editing
EP3114227B1 (en) 2014-03-05 2021-07-21 Editas Medicine, Inc. Crispr/cas-related methods and compositions for treating usher syndrome and retinitis pigmentosa
US11339437B2 (en) 2014-03-10 2022-05-24 Editas Medicine, Inc. Compositions and methods for treating CEP290-associated disease
WO2015138510A1 (en) 2014-03-10 2015-09-17 Editas Medicine., Inc. Crispr/cas-related methods and compositions for treating leber's congenital amaurosis 10 (lca10)
US11141493B2 (en) 2014-03-10 2021-10-12 Editas Medicine, Inc. Compositions and methods for treating CEP290-associated disease
JP6756700B2 (en) 2014-03-18 2020-09-16 ユニバーシティ オブ マサチューセッツ RAAV-based compositions and methods for treating amyotrophic lateral sclerosis
WO2015148863A2 (en) 2014-03-26 2015-10-01 Editas Medicine, Inc. Crispr/cas-related methods and compositions for treating sickle cell disease
EP3126495A1 (en) 2014-04-02 2017-02-08 Editas Medicine, Inc. Crispr/cas-related methods and compositions for treating primary open angle glaucoma
WO2016022363A2 (en) 2014-07-30 2016-02-11 President And Fellows Of Harvard College Cas9 proteins including ligand-dependent inteins
ES2731437T3 (en) 2014-11-21 2019-11-15 Regeneron Pharma Methods and compositions for directed genetic modification through the use of guide RNA pairs
US11180793B2 (en) 2015-04-24 2021-11-23 Editas Medicine, Inc. Evaluation of Cas9 molecule/guide RNA molecule complexes
MX2017014665A (en) * 2015-05-16 2018-04-24 Genzyme Corp Gene editing of deep intronic mutations.
WO2016205825A1 (en) * 2015-06-19 2016-12-22 Precision Biosciences, Inc. Self-limiting viral vectors encoding nucleases
IL258821B (en) 2015-10-23 2022-07-01 Harvard College Nucleobase editors and uses thereof
US11512311B2 (en) 2016-03-25 2022-11-29 Editas Medicine, Inc. Systems and methods for treating alpha 1-antitrypsin (A1AT) deficiency
MX2018014172A (en) 2016-05-20 2019-08-22 Regeneron Pharma Methods for breaking immunological tolerance using multiple guide rnas.
WO2018026976A1 (en) * 2016-08-02 2018-02-08 Editas Medicine, Inc. Compositions and methods for treating cep290 associated disease
KR20250103795A (en) 2016-08-03 2025-07-07 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 Adenosine nucleobase editors and uses thereof
CA3033327A1 (en) 2016-08-09 2018-02-15 President And Fellows Of Harvard College Programmable cas9-recombinase fusion proteins and uses thereof
WO2018039438A1 (en) 2016-08-24 2018-03-01 President And Fellows Of Harvard College Incorporation of unnatural amino acids into proteins using base editing
IT201600102542A1 (en) * 2016-10-12 2018-04-12 Univ Degli Studi Di Trento Plasmid and lentiviral system containing a self-limiting Cas9 circuit that increases its safety.
JP7588390B2 (en) 2016-10-14 2024-11-22 プレジデント アンド フェローズ オブ ハーバード カレッジ AAV Delivery of Nucleobase Editors
CA3046076A1 (en) 2016-12-05 2018-06-14 Editas Medicine, Inc. Systems and methods for one-shot guide rna (ogrna) targeting of endogenous and source dna
WO2018119359A1 (en) 2016-12-23 2018-06-28 President And Fellows Of Harvard College Editing of ccr5 receptor gene to protect against hiv infection
CN110662556A (en) 2017-03-09 2020-01-07 哈佛大学的校长及成员们 Cancer vaccine
WO2018165504A1 (en) 2017-03-09 2018-09-13 President And Fellows Of Harvard College Suppression of pain by gene editing
JP2020510439A (en) 2017-03-10 2020-04-09 プレジデント アンド フェローズ オブ ハーバード カレッジ Base-editing factor from cytosine to guanine
EP3596217A1 (en) 2017-03-14 2020-01-22 Editas Medicine, Inc. Systems and methods for the treatment of hemoglobinopathies
BR112019019655A2 (en) 2017-03-23 2020-04-22 Harvard College nucleobase editors comprising nucleic acid programmable dna binding proteins
US11859179B2 (en) 2017-05-09 2024-01-02 University Of Massachusetts Methods of treating amyotrophic lateral sclerosis (ALS)
EP3622070A2 (en) 2017-05-10 2020-03-18 Editas Medicine, Inc. Crispr/rna-guided nuclease systems and methods
WO2018209320A1 (en) 2017-05-12 2018-11-15 President And Fellows Of Harvard College Aptazyme-embedded guide rnas for use with crispr-cas9 in genome editing and transcriptional activation
JP2020534795A (en) 2017-07-28 2020-12-03 プレジデント アンド フェローズ オブ ハーバード カレッジ Methods and Compositions for Evolving Base Editing Factors Using Phage-Supported Continuous Evolution (PACE)
US11319532B2 (en) 2017-08-30 2022-05-03 President And Fellows Of Harvard College High efficiency base editors comprising Gam
WO2019060686A1 (en) 2017-09-22 2019-03-28 University Of Massachusetts Sod1 dual expression vectors and uses thereof
KR20250107288A (en) 2017-10-16 2025-07-11 더 브로드 인스티튜트, 인코퍼레이티드 Uses of adenosine base editors
US10662425B2 (en) 2017-11-21 2020-05-26 Crispr Therapeutics Ag Materials and methods for treatment of autosomal dominant retinitis pigmentosa
WO2019118949A1 (en) 2017-12-15 2019-06-20 The Broad Institute, Inc. Systems and methods for predicting repair outcomes in genetic engineering
CA3093702A1 (en) 2018-03-14 2019-09-19 Editas Medicine, Inc. Systems and methods for the treatment of hemoglobinopathies
EP4186921A1 (en) * 2018-03-23 2023-05-31 The Trustees of Columbia University in the City of New York Gene editing for autosomal dominant diseases
BR112020019079A2 (en) * 2018-03-23 2020-12-29 Massachusetts Eye And Ear Infirmary CRISPR / CAS9 MEDIUM JUMP APPROACH FOR USHER SYNDROME ASSOCIATED WITH USH2A
EP3781174A4 (en) 2018-04-09 2022-01-26 Allen Institute RESCUING VOLTAGE-SENSITIVE SODIUM CHANNEL FUNCTION IN INHIBITOR NEURONS
WO2019226953A1 (en) 2018-05-23 2019-11-28 The Broad Institute, Inc. Base editors and uses thereof
WO2019232253A1 (en) 2018-05-30 2019-12-05 The Regents Of The University Of California Gene editing of monogenic disorders in human hematopoietic stem cells -- correction of x-linked agammaglobulinemia (xla)
GB201809588D0 (en) * 2018-06-12 2018-07-25 Univ Bristol Materials and methods for modulating intraocular and intracranial pressure
AU2019314208A1 (en) * 2018-08-02 2021-02-18 Editas Medicine, Inc. Compositions and methods for treating CEP290-associated disease
KR102103103B1 (en) 2018-08-16 2020-04-21 (주)라트바이오 Transgenic animals and transgenic embryos producing an engineered nuclease
AR116569A1 (en) 2018-10-01 2021-05-19 Ultragenyx Pharmaceutical Inc GENE THERAPY TO TREAT PROPIONIC ACIDEMIA
AU2019358806B2 (en) 2018-10-08 2025-06-05 Allen Institute Artificial expression constructs for selectively modulating gene expression in interneurons
WO2020092453A1 (en) 2018-10-29 2020-05-07 The Broad Institute, Inc. Nucleobase editors comprising geocas9 and uses thereof
CN113302201A (en) * 2018-11-21 2021-08-24 斯特里迪比奥公司 Recombinant viral vectors and nucleic acids for producing the same
IT201800020230A1 (en) * 2018-12-19 2020-06-19 Univ Degli Studi Di Siena CRISPR-Cas system for gene therapy.
US12351837B2 (en) 2019-01-23 2025-07-08 The Broad Institute, Inc. Supernegatively charged proteins and uses thereof
US20220047618A1 (en) * 2019-02-28 2022-02-17 Regeneron Pharmaceuticals, Inc. Adeno-associated virus vectors for the delivery of therapeutics
EP3942042A1 (en) 2019-03-19 2022-01-26 The Broad Institute, Inc. Methods and compositions for editing nucleotide sequences
PH12021552383A1 (en) * 2019-03-27 2022-06-13 Res Inst Nationwide Childrens Hospital Generation of chimeric antigen receptor (car)-primary nk cells for cancer immunotherapy using a combination of cas9/rnp and aav viruses
WO2020197330A1 (en) * 2019-03-28 2020-10-01 주식회사 툴젠 Composition for treating hemophilia by means of blood coagulation factor viii gene inversion correction
JP2022529650A (en) * 2019-04-15 2022-06-23 ザ・トラステイーズ・オブ・ザ・ユニバーシテイ・オブ・ペンシルベニア Compositions for regulating and self-inactivating enzyme expression and methods for regulating off-target activity of enzymes
EP3956349A1 (en) 2019-04-17 2022-02-23 The Broad Institute, Inc. Adenine base editors with reduced off-target effects
US12435330B2 (en) 2019-10-10 2025-10-07 The Broad Institute, Inc. Methods and compositions for prime editing RNA
CN111370055B (en) * 2020-03-05 2023-05-23 中南大学 Method for establishing intron retention prediction model and its prediction method
IL296662A (en) * 2020-03-24 2022-11-01 Generation Bio Co Non-viral DNA vectors and their use for expression of Gauche cure
WO2021226558A1 (en) 2020-05-08 2021-11-11 The Broad Institute, Inc. Methods and compositions for simultaneous editing of both strands of a target double-stranded nucleotide sequence
US12171813B2 (en) 2021-02-05 2024-12-24 Christiana Care Gene Editing Institute, Inc. Methods of and compositions for reducing gene expression and/or activity
WO2022187571A1 (en) * 2021-03-04 2022-09-09 Research Institute At Nationwide Children's Hospital Products and methods for treatment of dystrophin-based myopathies using crispr-cas9 to correct dmd exon duplications
US20220325298A1 (en) * 2021-04-12 2022-10-13 University Of Pittsburgh - Of The Commonwealth System Of Higher Education Crispr epigenetic therapeutics for pain management
JP7780172B2 (en) * 2021-07-30 2025-12-04 国立研究開発法人理化学研究所 Mutations in the CEP290 gene in amyotrophic lateral sclerosis
CN114306277B (en) * 2021-11-02 2023-08-04 中国人民解放军空军军医大学 PSMA-targeted macrophage membrane-wrapped bionic nano-drug carrier and application thereof
EP4223877A1 (en) 2022-02-08 2023-08-09 Eberhard Karls Universität Tübingen Medizinische Fakultät System and method for editing genomic dna to modulate splicing
WO2025135916A1 (en) * 2023-12-22 2025-06-26 주식회사 툴젠 Cas9 protein variant with low immunogenicity

Family Cites Families (41)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4217344A (en) 1976-06-23 1980-08-12 L'oreal Compositions containing aqueous dispersions of lipid spheres
US4235871A (en) 1978-02-24 1980-11-25 Papahadjopoulos Demetrios P Method of encapsulating biologically active materials in lipid vesicles
US4186183A (en) 1978-03-29 1980-01-29 The United States Of America As Represented By The Secretary Of The Army Liposome carriers in chemotherapy of leishmaniasis
US4261975A (en) 1979-09-19 1981-04-14 Merck & Co., Inc. Viral liposome particle
US4485054A (en) 1982-10-04 1984-11-27 Lipoderm Pharmaceuticals Limited Method of encapsulating biologically active materials in multilamellar lipid vesicles (MLV)
US4501728A (en) 1983-01-06 1985-02-26 Technology Unlimited, Inc. Masking of liposomes from RES recognition
US5049386A (en) 1985-01-07 1991-09-17 Syntex (U.S.A.) Inc. N-ω,(ω-1)-dialkyloxy)- and N-(ω,(ω-1)-dialkenyloxy)Alk-1-YL-N,N,N-tetrasubstituted ammonium lipids and uses therefor
US4897355A (en) 1985-01-07 1990-01-30 Syntex (U.S.A.) Inc. N[ω,(ω-1)-dialkyloxy]- and N-[ω,(ω-1)-dialkenyloxy]-alk-1-yl-N,N,N-tetrasubstituted ammonium lipids and uses therefor
US4946787A (en) 1985-01-07 1990-08-07 Syntex (U.S.A.) Inc. N-(ω,(ω-1)-dialkyloxy)- and N-(ω,(ω-1)-dialkenyloxy)-alk-1-yl-N,N,N-tetrasubstituted ammonium lipids and uses therefor
US4774085A (en) 1985-07-09 1988-09-27 501 Board of Regents, Univ. of Texas Pharmaceutical administration systems containing a mixture of immunomodulators
US4837028A (en) 1986-12-24 1989-06-06 Liposome Technology, Inc. Liposomes with enhanced circulation time
US5264618A (en) 1990-04-19 1993-11-23 Vical, Inc. Cationic lipids for intracellular delivery of biologically active molecules
AU7979491A (en) 1990-05-03 1991-11-27 Vical, Inc. Intracellular delivery of biologically active substances by means of self-assembling lipid complexes
JP2001500015A (en) 1996-09-06 2001-01-09 トラステイーズ・オブ・ザ・ユニバーシテイ・オブ・ペンシルベニア Method for producing inducible recombinant adeno-associated virus using T7 polymerase
US6566118B1 (en) 1997-09-05 2003-05-20 Targeted Genetics Corporation Methods for generating high titer helper-free preparations of released recombinant AAV vectors
US6995006B2 (en) 1997-09-05 2006-02-07 Targeted Genetics Corporation Methods for generating high titer helper-free preparations of released recombinant AAV vectors
JP4827353B2 (en) 1999-08-09 2011-11-30 ターゲティッド ジェネティクス コーポレイション Increased expression of single-stranded heterologous nucleotide sequences from recombinant viral vectors by designing sequences to form intrastrand base pairs
WO2001092551A2 (en) 2000-06-01 2001-12-06 University Of North Carolina At Chapel Hill Duplexed parvovirus vectors
US6723551B2 (en) 2001-11-09 2004-04-20 The United States Of America As Represented By The Department Of Health And Human Services Production of adeno-associated virus in insect cells
SG168422A1 (en) 2001-11-13 2011-02-28 Univ Pennsylvania A method of detecting and/or identifying adeno-associated virus (aav) sequences and isolating novel sequences identified thereby
AU2003295312B2 (en) 2002-05-01 2008-08-14 University Of Florida Research Foundation, Inc. Improved rAAV expression systems for genetic modification of specific capsid proteins
JP4559429B2 (en) 2003-05-21 2010-10-06 ジェンザイム・コーポレーション Method for producing a recombinant AAV virion preparation substantially free of empty capsids
EP1486567A1 (en) 2003-06-11 2004-12-15 Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts Improved adeno-associated virus (AAV) vector for gene therapy
WO2005056762A2 (en) * 2003-12-05 2005-06-23 University Of Iowa Research Foundation Truncated cmv promoters and vectors containing same
US7765583B2 (en) 2005-02-28 2010-07-27 France Telecom System and method for managing virtual user domains
WO2006119432A2 (en) 2005-04-29 2006-11-09 The Government Of The U.S.A., As Rep. By The Sec., Dept. Of Health & Human Services Isolation, cloning and characterization of new adeno-associated virus (aav) serotypes
EP2007795B1 (en) 2006-03-30 2016-11-16 The Board Of Trustees Of The Leland Stanford Junior University Aav capsid proteins
US20100081707A1 (en) 2008-02-21 2010-04-01 Ali Robin R Devices and methods for delivering polynucleotides into retinal cells of the macula and fovea
WO2009121536A1 (en) 2008-04-02 2009-10-08 Fondazione Telethon Method of treating genetic disorders
SMT201800554T1 (en) 2009-06-16 2018-11-09 Genzyme Corp Improved methods for purification of recombinant aav vectors
WO2012099540A1 (en) * 2011-01-17 2012-07-26 Agency For Science, Technology And Research Cmv promoter variants
SG10202007803QA (en) 2011-02-17 2020-09-29 Univ Pennsylvania Compositions and methods for altering tissue specificity and improving aav9-mediated gene transfer
US8697359B1 (en) 2012-12-12 2014-04-15 The Broad Institute, Inc. CRISPR-Cas systems and methods for altering expression of gene products
KR20250012194A (en) * 2013-06-17 2025-01-23 더 브로드 인스티튜트, 인코퍼레이티드 Delivery, use and therapeutic applications of the crispr-cas systems and compositions for targeting disorders and diseases using viral components
JP6625971B2 (en) * 2013-06-17 2019-12-25 ザ・ブロード・インスティテュート・インコーポレイテッド Delivery, engineering and optimization of tandem guide systems, methods and compositions for array manipulation
CA2930015A1 (en) 2013-11-07 2015-05-14 Editas Medicine, Inc. Crispr-related methods and compositions with governing grnas
WO2015089351A1 (en) * 2013-12-12 2015-06-18 The Broad Institute Inc. Compositions and methods of use of crispr-cas systems in nucleotide repeat disorders
WO2015138510A1 (en) * 2014-03-10 2015-09-17 Editas Medicine., Inc. Crispr/cas-related methods and compositions for treating leber's congenital amaurosis 10 (lca10)
MX2017014665A (en) * 2015-05-16 2018-04-24 Genzyme Corp Gene editing of deep intronic mutations.
WO2016205825A1 (en) * 2015-06-19 2016-12-22 Precision Biosciences, Inc. Self-limiting viral vectors encoding nucleases
WO2017136335A1 (en) * 2016-02-01 2017-08-10 The Regents Of The University Of California Self-inactivating endonuclease-encoding nucleic acids and methods of using the same

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