Directed integration of new insulated lentiviral vectors to heterochromatin towards safer gene transfer to stem cells

Détails

ID Serval
serval:BIB_0892D6FCDE62
Type
Actes de conférence (partie): contribution originale à la littérature scientifique, publiée à l'occasion de conférences scientifiques, dans un ouvrage de compte-rendu (proceedings), ou dans l'édition spéciale d'un journal reconnu (conference proceedings).
Sous-type
Poster: résume de manière illustrée et sur une page unique les résultats d'un projet de recherche. Les résumés de poster doivent être entrés sous "Abstract" et non "Poster".
Collection
Publications
Titre
Directed integration of new insulated lentiviral vectors to heterochromatin towards safer gene transfer to stem cells
Titre de la conférence
ESGCT, DGGT, GSZ, and ISCT 2009 Poster Presentations
Auteur(s)
Artus A., Duros C., Botbol Y., Gaussin A., Mermod N., Lavigne M., Cohen-Haguenauer O.
Organisation
Abstracts, Combined Meeting 2009, November 20-25, 2009, Hannover, Germany, Convention Center at Hannover Fairground XVIIth Annual Congress of the European Society of Gene and Cell Therapy, 16th Annual Meeting of the German Society of Gene Therapy, 4th Annual Congress of the German Society for Stem Cell Research, Co-organized by the European Branch of the International Society for Cellular Therapy
ISBN
1043-0342
Statut éditorial
Publié
Date de publication
2009
Peer-reviewed
Oui
Volume
20
Série
Human Gene Therapy
Pages
1502-1502
Langue
anglais
Notes
Publication type : Meeting Abstract
Résumé
The need for better gene transfer systems towards improved
risk=benefit balance for patients remains a major challenge in
the clinical translation of gene therapy (GT). We have investigated
the improvement of integrating vectors safety in
combining (i) new short synthetic genetic insulator elements
(GIE) and (ii) directing genetic integration to heterochromatin.
We have designed SIN-insulated retrovectors with two candidate
GIEs and could identify a specific combination of insulator
2 repeats which translates into best functional activity,
high titers and boundary effect in both gammaretro (p20) and
lentivectors (DCaro4) (see Duros et al, abstract ibid). Since
GIEs are believed to shield the transgenic cassette from inhibitory
effects and silencing, DCaro4 has been further tested
with chimeric HIV-1 derived integrases which comprise C-ter
chromodomains targeting heterochromatin through either
histone H3 (ML6chimera) or methylatedCpGislands (ML10).
With DCaro4 only and both chimeras, a homogeneous expression
is evidenced in over 20% of the cells which is sustained
over time. With control lentivectors, less than 2% of
cells express GFP as compared to background using a control
double-mutant in both catalytic and ledgf binding-sites; in
addition, a two-times increase of expression can be induced
with histone deacetylase inhibitors. Our approach could significantly
reduce integration into open chromatin sensitive
sites in stem cells at the time of transduction, a feature which
might significantly decrease subsequent genotoxicity, according
to X-SCIDs patients data.Work performed with the
support of EC-DG research within the FP6-Network of Excellence,
CLINIGENE: LSHB-CT-2006-018933
Web of science
Création de la notice
15/06/2010 10:39
Dernière modification de la notice
20/08/2019 12:30
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