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WO2024227047A3 - Modified guide rna - Google Patents

Modified guide rna Download PDF

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Publication number
WO2024227047A3
WO2024227047A3 PCT/US2024/026601 US2024026601W WO2024227047A3 WO 2024227047 A3 WO2024227047 A3 WO 2024227047A3 US 2024026601 W US2024026601 W US 2024026601W WO 2024227047 A3 WO2024227047 A3 WO 2024227047A3
Authority
WO
WIPO (PCT)
Prior art keywords
modified
target
guide rna
modified guide
present
Prior art date
Legal status (The legal status 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 status listed.)
Pending
Application number
PCT/US2024/026601
Other languages
French (fr)
Other versions
WO2024227047A2 (en
Inventor
Brian CAFFERTY
Ho YAU
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Beam Therapeutics Inc
Original Assignee
Beam Therapeutics Inc
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 Beam Therapeutics Inc filed Critical Beam Therapeutics Inc
Priority to CN202480027660.0A priority Critical patent/CN121079412A/en
Priority to AU2024261906A priority patent/AU2024261906A1/en
Publication of WO2024227047A2 publication Critical patent/WO2024227047A2/en
Publication of WO2024227047A3 publication Critical patent/WO2024227047A3/en
Anticipated expiration legal-status Critical
Pending legal-status Critical Current

Links

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
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/20—Type of nucleic acid involving clustered regularly interspaced short palindromic repeats [CRISPR]
    • 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
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/315—Phosphorothioates
    • 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
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/344—Position-specific modifications, e.g. on every purine, at the 3'-end
    • 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
    • C12N2320/00—Applications; Uses
    • C12N2320/50—Methods for regulating/modulating their activity
    • C12N2320/52—Methods for regulating/modulating their activity modulating the physical stability, e.g. GC-content

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Organic Chemistry (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biophysics (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present invention relates to modified gRNA molecules, compositions and methods for site specific gene editing and genomic modification, such as DNA cleavage, and gene activation or repression. The present modified guide RNAs have modified secondary structure (e.g., long upper stem and a modified hairpin structure), which target the target DNA sequence specifically with reduced off-target activity.
PCT/US2024/026601 2023-04-28 2024-04-26 Modified guide rna Pending WO2024227047A2 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
CN202480027660.0A CN121079412A (en) 2023-04-28 2024-04-26 Modified guide RNAs
AU2024261906A AU2024261906A1 (en) 2023-04-28 2024-04-26 Modified guide rna

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202363462873P 2023-04-28 2023-04-28
US63/462,873 2023-04-28

Publications (2)

Publication Number Publication Date
WO2024227047A2 WO2024227047A2 (en) 2024-10-31
WO2024227047A3 true WO2024227047A3 (en) 2024-12-19

Family

ID=91334660

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2024/026601 Pending WO2024227047A2 (en) 2023-04-28 2024-04-26 Modified guide rna

Country Status (3)

Country Link
CN (1) CN121079412A (en)
AU (1) AU2024261906A1 (en)
WO (1) WO2024227047A2 (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020051562A2 (en) 2018-09-07 2020-03-12 Beam Therapeutics Inc. Compositions and methods for improving base editing

Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016089433A1 (en) * 2014-12-03 2016-06-09 Agilent Technologies, Inc. Guide rna with chemical modifications
WO2017044776A1 (en) * 2015-09-10 2017-03-16 Texas Tech University System Single-guide rna (sgrna) with improved knockout efficiency
WO2017068377A1 (en) * 2015-10-23 2017-04-27 Silence Therapeutics (London) Ltd Modified guide rnas, methods and uses
WO2018107028A1 (en) * 2016-12-08 2018-06-14 Intellia Therapeutics, Inc. Modified guide rnas
WO2019126037A1 (en) * 2017-12-19 2019-06-27 City Of Hope Modified tracrrnas grnas, and uses thereof
WO2019183000A1 (en) * 2018-03-19 2019-09-26 University Of Massachusetts Modified guide rnas for crispr genome editing
WO2021113494A1 (en) * 2019-12-03 2021-06-10 Beam Therapeutics Inc. Synthetic guide rna, compositions, methods, and uses thereof
WO2022248454A1 (en) * 2021-05-27 2022-12-01 MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. Novel crispr grnas
WO2023245141A2 (en) * 2022-06-15 2023-12-21 Beam Therapeutics Inc. Compositions and methods for reducing complement activation
WO2024006772A2 (en) * 2022-06-27 2024-01-04 Beam Therapeutics Inc. Adenosine deaminase base editors and methods for use thereof
WO2024042489A1 (en) * 2022-08-25 2024-02-29 LifeEDIT Therapeutics, Inc. Chemical modification of guide rnas with locked nucleic acid for rna guided nuclease-mediated gene editing

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US6043060A (en) 1996-11-18 2000-03-28 Imanishi; Takeshi Nucleotide analogues
JP3756313B2 (en) 1997-03-07 2006-03-15 武 今西 Novel bicyclonucleosides and oligonucleotide analogues
SI20474A (en) 1998-05-26 2001-08-31 Icn Pharmaceuticals, Inc. Novel nucleosides having bicyclic sugar moiety
CA2368135C (en) 1999-03-18 2010-06-08 Exiqon A/S Xylo-lna analogues
WO2000056746A2 (en) 1999-03-24 2000-09-28 Exiqon A/S Improved synthesis of [2.2.1]bicyclo nucleosides
PT1178999E (en) 1999-05-04 2007-06-26 Santaris Pharma As L-ribo-lna analogues
AU5429000A (en) 1999-06-25 2001-01-31 Sankyo Company Limited Novel bicyclonucleoside derivatives
JP4151751B2 (en) 1999-07-22 2008-09-17 第一三共株式会社 New bicyclonucleoside analogues
CA2504694C (en) 2002-11-05 2013-10-01 Isis Pharmaceuticals, Inc. Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation
JP4731324B2 (en) 2003-08-28 2011-07-20 武 今西 N-O bond cross-linked novel artificial nucleic acid
WO2005027962A1 (en) 2003-09-18 2005-03-31 Isis Pharmaceuticals, Inc. 4’-thionucleosides and oligomeric compounds
ES2516815T3 (en) 2006-01-27 2014-10-31 Isis Pharmaceuticals, Inc. Analogs of bicyclic nucleic acids modified at position 6
US20100190837A1 (en) 2007-02-15 2010-07-29 Isis Pharmaceuticals, Inc. 5'-Substituted-2-F' Modified Nucleosides and Oligomeric Compounds Prepared Therefrom
WO2008150729A2 (en) 2007-05-30 2008-12-11 Isis Pharmaceuticals, Inc. N-substituted-aminomethylene bridged bicyclic nucleic acid analogs
EP2173760B2 (en) 2007-06-08 2015-11-04 Isis Pharmaceuticals, Inc. Carbocyclic bicyclic nucleic acid analogs
AU2008272918B2 (en) 2007-07-05 2012-09-13 Isis Pharmaceuticals, Inc. 6-disubstituted bicyclic nucleic acid analogs
US12043852B2 (en) 2015-10-23 2024-07-23 President And Fellows Of Harvard College Evolved Cas9 proteins for gene editing
KR20250103795A (en) 2016-08-03 2025-07-07 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 Adenosine nucleobase editors and uses thereof
KR20230158531A (en) 2021-03-23 2023-11-20 빔 테라퓨틱스, 인크. Novel CRISPR enzymes, methods, systems and uses thereof
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Patent Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016089433A1 (en) * 2014-12-03 2016-06-09 Agilent Technologies, Inc. Guide rna with chemical modifications
WO2017044776A1 (en) * 2015-09-10 2017-03-16 Texas Tech University System Single-guide rna (sgrna) with improved knockout efficiency
WO2017068377A1 (en) * 2015-10-23 2017-04-27 Silence Therapeutics (London) Ltd Modified guide rnas, methods and uses
WO2018107028A1 (en) * 2016-12-08 2018-06-14 Intellia Therapeutics, Inc. Modified guide rnas
WO2019126037A1 (en) * 2017-12-19 2019-06-27 City Of Hope Modified tracrrnas grnas, and uses thereof
WO2019183000A1 (en) * 2018-03-19 2019-09-26 University Of Massachusetts Modified guide rnas for crispr genome editing
WO2021113494A1 (en) * 2019-12-03 2021-06-10 Beam Therapeutics Inc. Synthetic guide rna, compositions, methods, and uses thereof
WO2022248454A1 (en) * 2021-05-27 2022-12-01 MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. Novel crispr grnas
WO2023245141A2 (en) * 2022-06-15 2023-12-21 Beam Therapeutics Inc. Compositions and methods for reducing complement activation
WO2024006772A2 (en) * 2022-06-27 2024-01-04 Beam Therapeutics Inc. Adenosine deaminase base editors and methods for use thereof
WO2024042489A1 (en) * 2022-08-25 2024-02-29 LifeEDIT Therapeutics, Inc. Chemical modification of guide rnas with locked nucleic acid for rna guided nuclease-mediated gene editing

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
HAO YIN ET AL: "Structure-guided chemical modification of guide RNA enables potent non-viral in vivo genome editing", NATURE BIOTECHNOLOGY, vol. 35, no. 12, 13 November 2017 (2017-11-13), New York, pages 1179 - 1187, XP055484407, ISSN: 1087-0156, DOI: 10.1038/nbt.4005 *

Also Published As

Publication number Publication date
WO2024227047A2 (en) 2024-10-31
CN121079412A (en) 2025-12-05
AU2024261906A1 (en) 2025-10-23

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