WO2026077659A1 - Enrichissement en cellules souches hématopoïétiques génétiquement modifiées par édition épigénomique - Google Patents

Enrichissement en cellules souches hématopoïétiques génétiquement modifiées par édition épigénomique

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Publication number
WO2026077659A1
WO2026077659A1 PCT/EP2025/076396 EP2025076396W WO2026077659A1 WO 2026077659 A1 WO2026077659 A1 WO 2026077659A1 EP 2025076396 W EP2025076396 W EP 2025076396W WO 2026077659 A1 WO2026077659 A1 WO 2026077659A1
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Prior art keywords
cells
editing
epigenome
sequence
population
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Pending
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PCT/EP2025/076396
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English (en)
Inventor
Annarita MICCIO
Simone AMISTADI
Fotios Papadopoulos
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Assistance Publique Hopitaux de Paris APHP
Institut National de la Sante et de la Recherche Medicale INSERM
Fondation Imagine
Universite Paris Cite
Original Assignee
Assistance Publique Hopitaux de Paris APHP
Institut National de la Sante et de la Recherche Medicale INSERM
Fondation Imagine
Universite Paris Cite
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Application filed by Assistance Publique Hopitaux de Paris APHP, Institut National de la Sante et de la Recherche Medicale INSERM, Fondation Imagine, Universite Paris Cite filed Critical Assistance Publique Hopitaux de Paris APHP
Publication of WO2026077659A1 publication Critical patent/WO2026077659A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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    • C12N5/0647—Haematopoietic stem cells; Uncommitted or multipotent progenitors
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    • A61K35/28—Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • 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
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    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
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    • C12N9/14—Hydrolases (3)
    • C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
    • C12N9/22—Ribonucleases [RNase]; Deoxyribonucleases [DNase]
    • C12N9/222—Clustered regularly interspaced short palindromic repeats [CRISPR]-associated [CAS] enzymes
    • C12N9/226—Class 2 CAS enzyme complex, e.g. single CAS protein
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    • C07K2319/00—Fusion polypeptide
    • C07K2319/80—Fusion polypeptide containing a DNA binding domain, e.g. Lacl or Tet-repressor
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    • 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
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    • 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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    • C12N2510/00—Genetically modified cells

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Abstract

Ici, nous avons développé une stratégie d'édition épigénomique pour enrichir en HSPC éditées de base en régulant à la baisse de manière transitoire l'expression de CD33. CD33 est un marqueur de surface de la lignée myéloïde, qui est exprimé sur les CSH humaines ayant un potentiel régénératif élevé. Grâce à cette approche, la répression transitoire assurera une régulation à la baisse de CD33 uniquement dans le délai nécessaire pour sélectionner et enrichir en HSPC éditées de base. En particulier, la présente invention concerne un procédé d'édition d'une population de cellules eucaryotes comprenant la mise en contact de la population de cellules eucaryotes avec une plateforme d'édition épigénomique qui comprend (a) une ou plusieurs enzymes d'édition épigénomique, et (b) une ou plusieurs molécules d'ARN guide conçues pour guider l'enzyme d'édition épigénomique vers une séquence cible dans le gène codant pour le CD33 de façon à inactiver l'expression de CD33.
PCT/EP2025/076396 2024-09-17 2025-09-16 Enrichissement en cellules souches hématopoïétiques génétiquement modifiées par édition épigénomique Pending WO2026077659A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP24306532 2024-09-17
EP24306532.3 2024-09-17

Publications (1)

Publication Number Publication Date
WO2026077659A1 true WO2026077659A1 (fr) 2026-04-16

Family

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PCT/EP2025/076396 Pending WO2026077659A1 (fr) 2024-09-17 2025-09-16 Enrichissement en cellules souches hématopoïétiques génétiquement modifiées par édition épigénomique

Country Status (1)

Country Link
WO (1) WO2026077659A1 (fr)

Citations (21)

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WO2024165484A1 (fr) * 2023-02-06 2024-08-15 Institut National de la Santé et de la Recherche Médicale Enrichissement de cellules souches hématopoïétiques génétiquement modifiées par édition de bases multiplex

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