Supercharge Your Innovation With Domain-Expert AI Agents!

Permanent epigenetic gene silencing

A technology for silencing, target genes, in the field of gene silencing and/or epigenetic editing

Active Publication Date: 2017-08-29
OSPEDALE SAN RAFFAELE SRL +1
View PDF9 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these studies failed to demonstrate permanent epigenetic silencing in the absence of continuous expression of ATR, possibly due to the ability of selected effector domains to reestablish a self-propagating chromatin repression state at ATR target loci. Inner inability

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Permanent epigenetic gene silencing
  • Permanent epigenetic gene silencing
  • Permanent epigenetic gene silencing

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0547] To recapitulate the endogenous epigenetic mechanism that permanently silences endogenous retroviruses (ERVs) during development, we employed the human zinc finger protein 10 (ZNF10; Szulc, J. et al. (2006) Nat. Methods3: 109-16) and the catalytic domain of human DNA methyltransferase 3A (DNMT3A; Law, J.A. et al. (2010) Nat. Rev. Genet. 11:204-20). The amino acid sequences of these domains are shown in Table 1.

[0548] To test the activity and stability of gene silencing induced by these two effector domains, we used a tetracycline (tet) responsive system. We fused the two effector domains to the Escherichia coli tetracycline-controlled repressor (tetR) DNA-binding domain (Gossen, M. et al. (1992) Proc. Natl. Acad. Sci. USA89:5547-51), generating tetR:KRAB and tetR:DNMT3A artificial transcriptional repressors (ATR, hereinafter referred to as tetR:K and tetR:D3A, respectively). An advantage of the tetR system is that it allows temporal control of the binding of tetR to...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

A product comprising two or more artificial transcription repressors (ATRs), or polynucleotides encoding therefor, selected from groups (a), (b), (c) or (d): (a) an ATR comprising a DNA-binding domain operably linked to a KRAB domain or homologue thereof; (b) an ATR comprising a DNA-binding domain operably linked to a DNMT3A, DNMT3B or DNMT1 domain or homologue thereof; (c) an ATR comprising a DNA-binding domain operably linked to a DNMT3L domain or homologue thereof; and (d) an ATR comprising a DNA-binding domain operably linked to a SETDB1 domain or homologue thereof, wherein at least two of the ATRs are selected from different groups (a), (b), (c) or (d).

Description

field of invention [0001] The present invention relates to gene silencing and / or epigenetic editing. More specifically, the present invention relates to improved methods for silencing a gene of interest or for editing the epigenetic state of a genetic element of interest, including during gene therapy applications. Background of the invention [0002] Gene therapy involves incorporating genetic material into cells to treat or prevent disease. Genetic material can complement defective genes with functional copies of those genes, inactivate genes that are not functioning properly or introduce new therapeutic genes into cells. [0003] A classic example of gene therapy is gene replacement, in which a dysfunctional gene is replaced with a DNA sequence encoding a functional therapeutic gene (Naldini, L. (2011) Nat. Rev. Genet. 12:301-15; Kay, M.A. (2011) Nat .Rev.Genet.12:316-28; Biffi,A.et al.(2013)Science 341:1233158;Aiuti,A.etal.(2013)Science 341:1233151;Aiuti,A.et al.(2009)...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/85A61K35/12A61K38/17A61K38/45A61K48/00
CPCA61K35/12A61K38/1709A61K38/45A61K48/005C12N9/1007C12N15/85C07K14/4703C12Y201/01037C12Y201/01043C07K2319/80C12N2740/16043A61K38/00C12N9/22C12N2310/20C12N15/113C12N2800/80
Inventor L.纳尔迪尼A.L.隆巴尔多A.阿马比尔A.米格利亚拉
Owner OSPEDALE SAN RAFFAELE SRL
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com