CTF/NF1 transcription factors act as potent genetic insulators for integrating gene transfer vectors.

Détails

ID Serval
serval:BIB_CB32741F814E
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
CTF/NF1 transcription factors act as potent genetic insulators for integrating gene transfer vectors.
Périodique
Gene Therapy
Auteur(s)
Gaussin A., Modlich U., Bauche C., Niederländer N.J., Schambach A., Duros C., Artus A., Baum C., Cohen-Haguenauer O., Mermod N.
ISSN
1476-5462 (Electronic)
ISSN-L
0969-7128
Statut éditorial
Publié
Date de publication
2012
Volume
19
Numéro
1
Pages
15-24
Langue
anglais
Résumé
Gene transfer-based therapeutic approaches have greatly benefited from the ability of some viral vectors to efficiently integrate within the cell genome and ensure persistent transmission of newly acquired transgenes to the target cell progeny. However, integration of provirus has been associated with epigenetic repercussions that may influence the expression of both the transgene and cellular genes close to vector integration loci. The exploitation of genetic insulator elements may overcome both issues through their ability to act as barriers that limit transgene silencing and/or as enhancer-blockers preventing the activation of endogenous genes by the vector enhancer. We established quantitative plasmid-based assay systems to screen enhancer-blocker and barrier genetic elements. Short synthetic insulators that bind to nuclear factor-I protein family transcription factors were identified to exert both enhancer-blocker and barrier functions, and were compared to binding sites for the insulator protein CTCF (CCCTC-binding factor). Gamma-retroviral vectors enclosing these insulator elements were produced at titers similar to their non-insulated counterparts and proved to be less genotoxic in an in vitro immortalization assay, yielding lower activation of Evi1 oncogene expression and reduced clonal expansion of bone marrow cells.
Mots-clé
oncogene, insulators, CTF/NF1, CTCF, genome integration, genotoxicity
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/02/2011 11:27
Dernière modification de la notice
20/08/2019 15:46
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