WO2019153009A1 - Transcription regulatory elements and uses thereof - Google Patents

Transcription regulatory elements and uses thereof Download PDF

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Publication number
WO2019153009A1
WO2019153009A1 PCT/US2019/016692 US2019016692W WO2019153009A1 WO 2019153009 A1 WO2019153009 A1 WO 2019153009A1 US 2019016692 W US2019016692 W US 2019016692W WO 2019153009 A1 WO2019153009 A1 WO 2019153009A1
Authority
WO
WIPO (PCT)
Prior art keywords
nucleic acid
acid sequence
seq
regulatory element
segment
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.)
Ceased
Application number
PCT/US2019/016692
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English (en)
French (fr)
Inventor
John T. Gray
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.)
Astellas Gene Therapies Inc
Original Assignee
Audentes 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 Audentes Therapeutics Inc filed Critical Audentes Therapeutics Inc
Priority to US16/966,521 priority Critical patent/US12296026B2/en
Priority to EP19748361.3A priority patent/EP3749756A4/en
Priority to JP2020564045A priority patent/JP7381494B2/ja
Priority to CN201980015960.6A priority patent/CN111936621B/zh
Publication of WO2019153009A1 publication Critical patent/WO2019153009A1/en
Anticipated expiration legal-status Critical
Priority to JP2023188066A priority patent/JP7776477B2/ja
Ceased legal-status Critical Current

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    • 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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • 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
    • C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
    • 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
    • A61K48/0058—Nucleic acids adapted for tissue specific expression, e.g. having tissue specific promoters as part of a contruct
    • 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
    • C12N2830/00—Vector systems having a special element relevant for transcription
    • C12N2830/008—Vector systems having a special element relevant for transcription cell type or tissue specific enhancer/promoter combination
    • 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)
    • C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
    • C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)

Definitions

  • the first segment may have a nucleic acid sequence that is at least 90% identical to the nucleic acid sequence of SEQ ID NO: 2. In some embodiments, the first segment has a nucleic acid sequence that is at least 95% identical to the nucleic acid sequence of SEQ ID NO: 2. For example, the first segment may have the nucleic acid sequence of SEQ ID NO: 2.
  • a ligand that specifically binds to a protein may bind to the protein with a KD of up to 100 nM (e.g., between 1 pM and 100 nM).
  • a ligand that does not exhibit specific binding to another molecule or a domain thereof may exhibit a KD of greater than 100 nM (e.g., greater than 200 nM, 300 nM, 400 nM, 500 nM, 600 nm, 700 nM, 800 nM, 900 nM, 1 mM, 100 mM, 500 mM, or 1 mM) for that particular molecule or domain thereof.
  • a variety of assay formats may be used to determine the affinity of a ligand for a specific protein.
  • genes encoding a GAA polypeptide that may be used in conjunction with the compositions and methods described herein include genes encoding the wild-type GAA protein set forth in SEQ ID NO: 14, as well as functional GAA enzymes having at least 85% identical (e.g., 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.9%, or 100% identical) to the amino acid sequence of SEQ ID NO: 14.
  • adeno-associated virus (AAV) vectors were designed to target expression in distinct tissues (e.g., muscle and liver) across a range of doses in a mouse model of Pompe. Outcomes were compared following systemic administration in a Pompe mouse model for six adeno-associated virus (AAV) vectors designed to direct expression of the human acid alpha-glucosidase gene (hGAA) to distinct tissues and/or combinations of tissues across a range of doses. Vectors were selected with the optimal multi-tissue expression profile for translation to clinical trials of systemically administered AAV-GAA for treatment of Pompe disease.
  • AAV adeno-associated virus
  • GAA activity was assessed in muscle and liver tissue. To determine GAA activity in muscles, GAA activity was assessed one month post-dosing (see materials and methods) in quadriceps tissue from male (black dots) and female mice (grey triangles) for control- and vector-treated mice dosed at 1 x10 13 vg/kg (FIG. 2). To determine GAA activity in liver tissue, GAA activity was assessed one month post-dosing in liver tissue from male (black dots) and female mice (grey triangles) for control- and vector- treated mice dosed at 1 x10 13 vg/kg (FIG. 4).

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biomedical Technology (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Veterinary Medicine (AREA)
  • Virology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Microbiology (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Epidemiology (AREA)
  • Diabetes (AREA)
  • Immunology (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (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)
  • Medicinal Preparation (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
PCT/US2019/016692 2018-02-05 2019-02-05 Transcription regulatory elements and uses thereof Ceased WO2019153009A1 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
US16/966,521 US12296026B2 (en) 2018-02-05 2019-02-05 Transcription regulatory elements and uses thereof
EP19748361.3A EP3749756A4 (en) 2018-02-05 2019-02-05 ELEMENTS OF TRANSCRIPTION REGULATION AND ASSOCIATED USES
JP2020564045A JP7381494B2 (ja) 2018-02-05 2019-02-05 転写調節要素及びその使用
CN201980015960.6A CN111936621B (zh) 2018-02-05 2019-02-05 转录调控元件和它的用途
JP2023188066A JP7776477B2 (ja) 2018-02-05 2023-11-02 転写調節要素及びその使用

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201862626561P 2018-02-05 2018-02-05
US62/626,561 2018-02-05

Publications (1)

Publication Number Publication Date
WO2019153009A1 true WO2019153009A1 (en) 2019-08-08

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PCT/US2019/016692 Ceased WO2019153009A1 (en) 2018-02-05 2019-02-05 Transcription regulatory elements and uses thereof

Country Status (6)

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US (1) US12296026B2 (https=)
EP (1) EP3749756A4 (https=)
JP (2) JP7381494B2 (https=)
CN (1) CN111936621B (https=)
MA (1) MA51753A (https=)
WO (1) WO2019153009A1 (https=)

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021102107A1 (en) * 2019-11-19 2021-05-27 Asklepios Biopharmaceutical, Inc. Therapeutic adeno-associated virus comprising liver-specific promoters for treating pompe disease and lysosomal disorders
JP2021514201A (ja) * 2018-02-07 2021-06-10 ジェネトン ハイブリッド調節要素
WO2021165350A1 (en) * 2020-02-18 2021-08-26 Vrije Universiteit Brussel Novel combination of nucleic acid regulatory elements and methods and uses thereof
US11208458B2 (en) 2017-06-07 2021-12-28 Regeneron Pharmaceuticals, Inc. Compositions and methods for internalizing enzymes
US11517631B2 (en) 2018-08-20 2022-12-06 Ucl Business Ltd Factor IX encoding nucleotides
JP2022554141A (ja) * 2019-10-25 2022-12-28 オーデンツ セラピューティクス，インコーポレーテッド 糖原病を治療するための組成物及び方法
WO2023006890A1 (en) * 2021-07-28 2023-02-02 Vrije Universiteit Brussel Improving the efficacy of muscle-targeted gene therapy
US20230330266A1 (en) * 2020-08-24 2023-10-19 Combigene Ab Gene therapy for lipodystrophy
WO2023173078A3 (en) * 2022-03-11 2023-10-19 Homology Medicines, Inc. Bidirectional dual promoter expression vectors and uses thereof
WO2025004002A2 (en) 2023-06-30 2025-01-02 Takeda Pharmaceutical Company Limited Treatment of pompe disease
US12209262B2 (en) 2018-08-20 2025-01-28 Ucl Business Ltd Factor IX encoding nucleotides
US12252544B2 (en) 2018-05-17 2025-03-18 Regeneron Pharmaceuticals, Inc. Anti-CD63 antibodies, conjugates, and uses thereof
US12258597B2 (en) 2018-02-07 2025-03-25 Regeneron Pharmaceuticals, Inc. Methods and compositions for therapeutic protein delivery

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20210148273A (ko) * 2019-04-08 2021-12-07 제네똥 근육 발현을 위한 하이브리드 프로모터
WO2024006775A2 (en) * 2022-06-27 2024-01-04 Astellas Gene Therapies, Inc. Compositions and methods for the treatment of myotonic dystrophies
EP4598590A1 (en) * 2022-10-08 2025-08-13 Lingyi Biotech Co., Ltd. Construct for enhancing gene expression
CN118064436B (zh) * 2024-04-18 2024-07-26 上海凌医生物科技有限公司 一种增强基因表达的嵌合启动子

Citations (4)

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US20070161031A1 (en) * 2005-12-16 2007-07-12 The Board Of Trustees Of The Leland Stanford Junior University Functional arrays for high throughput characterization of gene expression regulatory elements
US20100120152A1 (en) * 2001-08-27 2010-05-13 Wooddell Christine I Methods for expression of transgenes
US20170218395A1 (en) * 2014-06-20 2017-08-03 University Of Florida Research Foundation, Inc. Methods of packaging multiple adeno-associated virus vectors
US20170275649A1 (en) * 2014-01-21 2017-09-28 Vrije Universiteit Brussel Muscle-Specific Nucleic Acid Regulatory Elements and Methods and Use Thereof

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EP1390490B1 (en) * 2001-05-24 2009-04-15 Genzyme Corporation Muscle-specific expression vectors
WO2006036502A2 (en) 2004-09-22 2006-04-06 St. Jude Children's Research Hospital Improved expression of factor ix in gene therapy vectors
KR20150020250A (ko) * 2012-06-19 2015-02-25 유니버시티 오브 플로리다 리서치 파운데이션, 인코포레이티드 당뇨병을 치료하기 위한 조성물 및 방법
CN105229144A (zh) * 2013-02-22 2016-01-06 细胞动力学国际有限公司 通过组合的遗传工程和化学工程经由正向编程产生肝细胞
EP3285788B1 (en) * 2015-04-23 2024-12-18 University of Massachusetts Modulation of aav vector transgene expression
TW202446416A (zh) * 2015-09-24 2024-12-01 美商拜奧馬林製藥公司 腺相關病毒因子viii載體、相關病毒粒子及包含其之治療調配物

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100120152A1 (en) * 2001-08-27 2010-05-13 Wooddell Christine I Methods for expression of transgenes
US20070161031A1 (en) * 2005-12-16 2007-07-12 The Board Of Trustees Of The Leland Stanford Junior University Functional arrays for high throughput characterization of gene expression regulatory elements
US20170275649A1 (en) * 2014-01-21 2017-09-28 Vrije Universiteit Brussel Muscle-Specific Nucleic Acid Regulatory Elements and Methods and Use Thereof
US20170218395A1 (en) * 2014-06-20 2017-08-03 University Of Florida Research Foundation, Inc. Methods of packaging multiple adeno-associated virus vectors

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11208458B2 (en) 2017-06-07 2021-12-28 Regeneron Pharmaceuticals, Inc. Compositions and methods for internalizing enzymes
US12215138B2 (en) 2017-06-07 2025-02-04 Regeneron Pharmaceuticals, Inc. Compositions and methods for internalizing enzymes
US12258597B2 (en) 2018-02-07 2025-03-25 Regeneron Pharmaceuticals, Inc. Methods and compositions for therapeutic protein delivery
JP7467356B2 (ja) 2018-02-07 2024-04-15 ジェネトン ハイブリッド調節要素
JP2024079819A (ja) * 2018-02-07 2024-06-11 ジェネトン ハイブリッド調節要素
JP2021514201A (ja) * 2018-02-07 2021-06-10 ジェネトン ハイブリッド調節要素
US12252544B2 (en) 2018-05-17 2025-03-18 Regeneron Pharmaceuticals, Inc. Anti-CD63 antibodies, conjugates, and uses thereof
US11517631B2 (en) 2018-08-20 2022-12-06 Ucl Business Ltd Factor IX encoding nucleotides
US12209262B2 (en) 2018-08-20 2025-01-28 Ucl Business Ltd Factor IX encoding nucleotides
JP2022554141A (ja) * 2019-10-25 2022-12-28 オーデンツ セラピューティクス，インコーポレーテッド 糖原病を治療するための組成物及び方法
CN116096895A (zh) * 2019-11-19 2023-05-09 阿斯克肋匹奥生物制药公司 用于治疗庞贝氏病和溶酶体紊乱的包含肝特异性启动子的治疗性腺相关病毒
WO2021102107A1 (en) * 2019-11-19 2021-05-27 Asklepios Biopharmaceutical, Inc. Therapeutic adeno-associated virus comprising liver-specific promoters for treating pompe disease and lysosomal disorders
WO2021165350A1 (en) * 2020-02-18 2021-08-26 Vrije Universiteit Brussel Novel combination of nucleic acid regulatory elements and methods and uses thereof
US20230330266A1 (en) * 2020-08-24 2023-10-19 Combigene Ab Gene therapy for lipodystrophy
WO2023006890A1 (en) * 2021-07-28 2023-02-02 Vrije Universiteit Brussel Improving the efficacy of muscle-targeted gene therapy
WO2023173078A3 (en) * 2022-03-11 2023-10-19 Homology Medicines, Inc. Bidirectional dual promoter expression vectors and uses thereof
WO2025004002A2 (en) 2023-06-30 2025-01-02 Takeda Pharmaceutical Company Limited Treatment of pompe disease

Also Published As

Publication number Publication date
JP7381494B2 (ja) 2023-11-15
MA51753A (fr) 2020-12-16
JP2024012479A (ja) 2024-01-30
JP7776477B2 (ja) 2025-11-26
US20210162073A1 (en) 2021-06-03
CN111936621B (zh) 2025-05-13
CN111936621A (zh) 2020-11-13
JP2021512649A (ja) 2021-05-20
EP3749756A4 (en) 2021-12-08
EP3749756A1 (en) 2020-12-16
US12296026B2 (en) 2025-05-13

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