CN113785063A - 用于治疗杜氏肌营养不良症的aav载体介导的大规模突变热点缺失 - Google Patents

用于治疗杜氏肌营养不良症的aav载体介导的大规模突变热点缺失 Download PDF

Info

Publication number
CN113785063A
CN113785063A CN202080028248.2A CN202080028248A CN113785063A CN 113785063 A CN113785063 A CN 113785063A CN 202080028248 A CN202080028248 A CN 202080028248A CN 113785063 A CN113785063 A CN 113785063A
Authority
CN
China
Prior art keywords
seq
vector
promoter
gene
grna
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
CN202080028248.2A
Other languages
English (en)
Chinese (zh)
Inventor
查尔斯·A·格斯巴赫
卡伦·布拉克拉克
杰奎琳·N·罗宾逊-哈姆
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.)
Duke University
Original Assignee
Duke University
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 Duke University filed Critical Duke University
Publication of CN113785063A publication Critical patent/CN113785063A/zh
Pending legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4707—Muscular dystrophy
    • C07K14/4708—Duchenne dystrophy
    • 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
    • C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/102—Mutagenizing nucleic acids
    • 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
    • C12N15/111—General methods applicable to biologically active non-coding nucleic acids
    • 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
    • C12N15/86—Viral vectors
    • 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]
    • 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
    • C12N2320/00—Applications; Uses
    • C12N2320/30—Special therapeutic applications
    • C12N2320/32—Special delivery means, e.g. tissue-specific
    • 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
    • C12N2510/00—Genetically modified 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
    • C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
    • C12N2750/00011—Details
    • C12N2750/14011—Parvoviridae
    • C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
    • C12N2750/14141—Use of virus, viral particle or viral elements as a vector
    • C12N2750/14143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
    • 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
    • C12N2800/00—Nucleic acids vectors
    • C12N2800/40—Systems of functionally co-operating vectors

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • Biophysics (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Medicinal Chemistry (AREA)
  • Virology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Cell Biology (AREA)
  • Mycology (AREA)
  • Toxicology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
CN202080028248.2A 2019-04-14 2020-04-14 用于治疗杜氏肌营养不良症的aav载体介导的大规模突变热点缺失 Pending CN113785063A (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201962833760P 2019-04-14 2019-04-14
US62/833,760 2019-04-14
PCT/US2020/028148 WO2020214609A1 (en) 2019-04-14 2020-04-14 Aav vector-mediated deletion of large mutational hotspot for treatment of duchenne muscular dystrophy

Publications (1)

Publication Number Publication Date
CN113785063A true CN113785063A (zh) 2021-12-10

Family

ID=72837591

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202080028248.2A Pending CN113785063A (zh) 2019-04-14 2020-04-14 用于治疗杜氏肌营养不良症的aav载体介导的大规模突变热点缺失

Country Status (17)

Country Link
US (1) US20220184229A1 (https=)
EP (1) EP3931331A4 (https=)
JP (2) JP2022529631A (https=)
KR (1) KR20210151916A (https=)
CN (1) CN113785063A (https=)
AR (1) AR118670A1 (https=)
AU (1) AU2020257898B2 (https=)
BR (1) BR112021020515A2 (https=)
CA (1) CA3137248A1 (https=)
CL (1) CL2021002680A1 (https=)
CO (1) CO2021013692A2 (https=)
EA (1) EA202192815A1 (https=)
IL (1) IL287163A (https=)
MX (1) MX2021012511A (https=)
SG (1) SG11202111172QA (https=)
TW (2) TWI887234B (https=)
WO (1) WO2020214609A1 (https=)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2024193704A1 (en) * 2023-03-22 2024-09-26 Huidagene Therapeutics Co., Ltd. Guide nucleic acids targeting dmd and uses thereof

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013163628A2 (en) 2012-04-27 2013-10-31 Duke University Genetic correction of mutated genes
US9828582B2 (en) 2013-03-19 2017-11-28 Duke University Compositions and methods for the induction and tuning of gene expression
WO2016130600A2 (en) 2015-02-09 2016-08-18 Duke University Compositions and methods for epigenome editing
WO2017035416A2 (en) 2015-08-25 2017-03-02 Duke University Compositions and methods of improving specificity in genomic engineering using rna-guided endonucleases
EP4089175A1 (en) 2015-10-13 2022-11-16 Duke University Genome engineering with type i crispr systems in eukaryotic cells
KR102787119B1 (ko) 2015-11-30 2025-03-27 듀크 유니버시티 유전자 편집에 의한 인간 디스트로핀 유전자의 교정을 위한 치료용 표적 및 사용 방법
US20190127713A1 (en) 2016-04-13 2019-05-02 Duke University Crispr/cas9-based repressors for silencing gene targets in vivo and methods of use
JP7490211B2 (ja) 2016-07-19 2024-05-27 デューク ユニバーシティ Ｃｐｆ１に基づくゲノム編集の治療適用
EP3740580A4 (en) 2018-01-19 2021-10-20 Duke University GENOME ENGINEERING WITH CRISPR-CAS SYSTEMS IN EUKARYONTS
US20230272428A1 (en) * 2019-12-16 2023-08-31 President And Fellows Of Harvard College Methods and compositions for correction of dmd mutations
US20230346978A1 (en) * 2020-04-14 2023-11-02 University Of Massachusetts Dcas13-mediated therapeutic rna base editing for in vivo gene therapy
WO2022087321A1 (en) * 2020-10-21 2022-04-28 Duke University Dual aav vector-mediated deletion of large mutational hotspot for treatment of duchenne muscular dystrophy
MX2024002988A (es) * 2021-09-08 2024-06-11 Flagship Pioneering Innovations Vi Llc Composiciones y metodos moduladores de la serpina.
IL317874A (en) 2022-06-24 2025-02-01 Tune Therapeutics Inc Compounds, systems and methods for reducing low density lipoproteins through targeted gene suppression
WO2025221969A2 (en) 2024-04-18 2025-10-23 Sarepta Therapeutics, Inc. Genetic constructs for gene editing

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014197748A2 (en) * 2013-06-05 2014-12-11 Duke University Rna-guided gene editing and gene regulation
WO2015195621A1 (en) * 2014-06-16 2015-12-23 The Johns Hopkins University Compositions and methods for the expression of crispr guide rnas using the h1 promoter
EP3199632A1 (en) * 2016-01-26 2017-08-02 ACIB GmbH Temperature-inducible crispr/cas system
CN108779466A (zh) * 2015-11-30 2018-11-09 杜克大学 用于通过基因编辑修正人肌营养不良蛋白基因的治疗靶标和使用方法
US20190038776A1 (en) * 2016-02-11 2019-02-07 The Regents Of The University Of California Methods and Compositions for Modifying a Mutant Dystrophin Gene in a Cell's Genome

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005035718A2 (en) * 2003-10-03 2005-04-21 Welgen, Inc. Biderectional promoters for small rna expression
AU2016344609B2 (en) * 2015-10-28 2022-05-12 Vertex Pharmaceuticals Incorporated Materials and methods for treatment of duchenne muscular dystrophy
US20190330626A1 (en) * 2016-07-15 2019-10-31 Ionis Pharmaceuticals, Inc. Compounds and methods for use in dystrophin transcript
US10687520B2 (en) * 2017-03-07 2020-06-23 The Board Of Regents Of The University Of Texas System Generation and correction of a humanized mouse model with a deletion of dystrophin exon 44
US11779653B2 (en) * 2017-09-29 2023-10-10 The Regents Of The University Of California Multi-armed polyrotaxane platform for protected nucleic acid delivery

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014197748A2 (en) * 2013-06-05 2014-12-11 Duke University Rna-guided gene editing and gene regulation
WO2015195621A1 (en) * 2014-06-16 2015-12-23 The Johns Hopkins University Compositions and methods for the expression of crispr guide rnas using the h1 promoter
CN108779466A (zh) * 2015-11-30 2018-11-09 杜克大学 用于通过基因编辑修正人肌营养不良蛋白基因的治疗靶标和使用方法
EP3199632A1 (en) * 2016-01-26 2017-08-02 ACIB GmbH Temperature-inducible crispr/cas system
US20190038776A1 (en) * 2016-02-11 2019-02-07 The Regents Of The University Of California Methods and Compositions for Modifying a Mutant Dystrophin Gene in a Cell's Genome

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
DAVID G OUSTEROUT等: "Multiplex CRISPR/Cas9-based genome editing for correction of dystrophin mutations that cause Duchenne muscular dystrophy", 《NAT COMMUN . 》, vol. 6, pages 6244, XP055196515, DOI: 10.1038/ncomms7244 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2024193704A1 (en) * 2023-03-22 2024-09-26 Huidagene Therapeutics Co., Ltd. Guide nucleic acids targeting dmd and uses thereof

Also Published As

Publication number Publication date
TW202104594A (zh) 2021-02-01
IL287163A (en) 2021-12-01
AR118670A1 (es) 2021-10-20
EP3931331A1 (en) 2022-01-05
CL2021002680A1 (es) 2022-07-15
EA202192815A1 (ru) 2022-01-24
US20220184229A1 (en) 2022-06-16
AU2020257898B2 (en) 2026-03-05
WO2020214609A1 (en) 2020-10-22
JP2022529631A (ja) 2022-06-23
AU2020257898A1 (en) 2021-11-04
BR112021020515A2 (pt) 2022-01-04
SG11202111172QA (en) 2021-11-29
KR20210151916A (ko) 2021-12-14
CA3137248A1 (en) 2020-10-22
CO2021013692A2 (es) 2022-01-17
TW202536186A (zh) 2025-09-16
JP2025087680A (ja) 2025-06-10
TWI887234B (zh) 2025-06-21
MX2021012511A (es) 2022-01-06
EP3931331A4 (en) 2022-11-30

Similar Documents

Publication Publication Date Title
JP7633699B2 (ja) Ｃｐｆ１に基づくゲノム編集の治療適用
TWI887234B (zh) 治療杜興氏（ｄｕｃｈｅｎｎｅ）肌肉失養症之大型突變熱點之ａａｖ載體介導之刪除
JP7517724B2 (ja) 遺伝子編集によるヒトジストロフィン遺伝子の修正用の治療標的および使用方法
JP7827288B2 (ja) ジストロフィン機能を修復するためのＣＲＩＳＰＲ／Ｃａｓをベースにしたゲノム編集組成物
EP3452498B1 (en) Crispr/cas-related compositions for treating duchenne muscular dystrophy
HK40112232A (zh) 用於通过基因编辑修正人肌营养不良蛋白基因的治疗靶标和使用方法
EA049120B1 (ru) Опосредуемая aav-вектором делеция крупной мутационной "горячей точки" для лечения мышечной дистрофии дюшенна
HK40004669B (en) Therapeutic applications of cpf1-based genome editing
HK40004669A (en) Therapeutic applications of cpf1-based genome editing
BR112018011133B1 (pt) Composições, polinucleotídeo isolado, vetores e kit

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination