WO2023235888A3 - Cpg-reduced polynucleotides, viral vectors and their use in therapy - Google Patents

Cpg-reduced polynucleotides, viral vectors and their use in therapy Download PDF

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Publication number
WO2023235888A3
WO2023235888A3 PCT/US2023/067901 US2023067901W WO2023235888A3 WO 2023235888 A3 WO2023235888 A3 WO 2023235888A3 US 2023067901 W US2023067901 W US 2023067901W WO 2023235888 A3 WO2023235888 A3 WO 2023235888A3
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WIPO (PCT)
Prior art keywords
cpg
reduced
polynucleotides
therapy
viral vectors
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PCT/US2023/067901
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French (fr)
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WO2023235888A2 (en
Inventor
Wenyuan ZHOU
Fred DEITER
Manuel MOHR
Cécile FORTUNY
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Scribe Therapeutics Inc.
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Publication of WO2023235888A2 publication Critical patent/WO2023235888A2/en
Publication of WO2023235888A3 publication Critical patent/WO2023235888A3/en

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    • 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
    • A61K48/0008—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 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition
    • A61K48/0025—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 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition wherein the non-active part clearly interacts with the delivered nucleic acid
    • A61K48/0041—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 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition wherein the non-active part clearly interacts with the delivered nucleic acid the non-active part being polymeric
    • 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
    • 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
    • C07K14/4702—Regulators; Modulating activity
    • C—CHEMISTRY; METALLURGY
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    • 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
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    • 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 RNAses, DNAses
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/09—Fusion polypeptide containing a localisation/targetting motif containing a nuclear localisation signal
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/40—Fusion polypeptide containing a tag for immunodetection, or an epitope for immunisation
    • C07K2319/41—Fusion polypeptide containing a tag for immunodetection, or an epitope for immunisation containing a Myc-tag
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/50—Fusion polypeptide containing protease site
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • 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
    • C12N15/1138—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 against receptors or cell surface proteins
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    • 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 [CRISPRs]
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2320/00—Applications; Uses
    • C12N2320/50—Methods for regulating/modulating their activity
    • C12N2320/53—Methods for regulating/modulating their activity reducing unwanted side-effects
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    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • 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

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Zoology (AREA)
  • Biomedical Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Biophysics (AREA)
  • Microbiology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Plant Pathology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Physics & Mathematics (AREA)
  • Virology (AREA)
  • Toxicology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (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)

Abstract

Provided herein are polynucleotides comprising CpG-reduced regulatory elements, CpG-reduced RNA coding sequences, and CpG-reduced protein coding sequences. In some embodiments, such polynucleotides comprise no more than about 10% CpG dinucleotides. Also provided herein are recombinant vectors comprising such CpG-reduced polynucleotides, and cells expressing such reduced polynucleotides. The CpG-reduced polynucleotides, when used in methods of treatment, are useful for reducing inflammatory responses during such treatment.
PCT/US2023/067901 2022-06-03 2023-06-03 COMPOSITIONS AND METHODS FOR CpG DEPLETION WO2023235888A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202263349009P 2022-06-03 2022-06-03
US63/349,009 2022-06-03

Publications (2)

Publication Number Publication Date
WO2023235888A2 WO2023235888A2 (en) 2023-12-07
WO2023235888A3 true WO2023235888A3 (en) 2024-01-04

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PCT/US2023/067901 WO2023235888A2 (en) 2022-06-03 2023-06-03 COMPOSITIONS AND METHODS FOR CpG DEPLETION

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050101017A1 (en) * 2003-11-10 2005-05-12 Wojtek Auerbach Method of improving gene targeting using a ubiquitin promoter
WO2018089527A1 (en) * 2016-11-09 2018-05-17 Intrexon Corporation Frataxin expression constructs
WO2021207415A1 (en) * 2020-04-07 2021-10-14 The Curators Of The University Of Missouri CpG-FREE ITRs FOR AAV GENE THERAPY
WO2021242785A1 (en) * 2020-05-26 2021-12-02 Expression Therapeutics, Llc Lentiviral system

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CA3142883A1 (en) 2019-06-07 2020-12-10 Benjamin OAKES Engineered casx systems
WO2020247883A2 (en) 2019-06-07 2020-12-10 Scribe Therapeutics Inc. Deep mutational evolution of biomolecules
JP2022547168A (en) 2019-09-09 2022-11-10 スクライブ・セラピューティクス・インコーポレイテッド Compositions and methods for use in immunotherapy
EP4028522A1 (en) 2019-09-09 2022-07-20 Scribe Therapeutics Inc. Compositions and methods for the targeting of sod1
US20230033866A1 (en) 2019-12-06 2023-02-02 Scribe Therapeutics Inc. Compositions and methods for the targeting of rhodopsin
JP2023504536A (en) 2019-12-06 2023-02-03 スクライブ・セラピューティクス・インコーポレイテッド particle delivery system
WO2021113769A1 (en) 2019-12-07 2021-06-10 Scribe Therapeutics Inc. Compositions and methods for the targeting of htt
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EP4256054A1 (en) 2020-12-03 2023-10-11 Scribe Therapeutics Inc. Engineered class 2 type v crispr systems
BR112023010717A2 (en) 2020-12-03 2023-10-03 Scribe Therapeutics Inc COMPOSITIONS AND METHODS FOR TARGETING BCL11A
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Patent Citations (4)

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Publication number Priority date Publication date Assignee Title
US20050101017A1 (en) * 2003-11-10 2005-05-12 Wojtek Auerbach Method of improving gene targeting using a ubiquitin promoter
WO2018089527A1 (en) * 2016-11-09 2018-05-17 Intrexon Corporation Frataxin expression constructs
WO2021207415A1 (en) * 2020-04-07 2021-10-14 The Curators Of The University Of Missouri CpG-FREE ITRs FOR AAV GENE THERAPY
WO2021242785A1 (en) * 2020-05-26 2021-12-02 Expression Therapeutics, Llc Lentiviral system

Non-Patent Citations (8)

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Title
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