Novel insulated gamma and lentis retroviral vectors towards safer genetic modification of stem cells

Détails

ID Serval
serval:BIB_F9F942D64015
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
Novel insulated gamma and lentis retroviral vectors towards safer genetic modification of stem cells
Titre de la conférence
ESGCT, DGGT, GSZ, and ISCT 2009 Poster Presentations
Auteur(s)
Duros C., Artus A., Gaussin A., Scholtz S., Mermod N., Schmidt M., von Kalle C., 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
1505-1505
Langue
anglais
Notes
Publication type : Meeting Abstract
Résumé
In otherwise successful gene therapy trials insertional
mutagenesis has resulted in leukemia. The identification of
new short synthetic genetic insulator elements (GIE) which
would both prevent such activation effects and shield the
transgene from silencing, is a main challenge. Previous attempts
with e.g. b-globin HS4, have met with poor efficacy
and genetic instability. We have investigated potential
improvement with two new candidate synthetic GIEs in
SIN-gamma and lentiviral vectors. With each constructs two
internal promoters have been tested: either the strong Fr-
MuLV-U3 or the housekeeping hPGK.We could identify a
specific combination of insulator 2 repeats which translates
into best functional activity, high titers and boundary effect in
both gammaretro and lentivectors. In target cells a dramatic
shift of expression is observed with an homogenous profile
the level of which strictly depends on the promoter strength.
These data remain stable in both HeLa cells over three
months and cord blood HSCs for two months, irrespective of
the multiplicity of infection (MOI). In comparison, control
native and SIN vectors expression levels show heterogeneous,
depend on the MOI and prove unstable. We have
undertaken genotoxicity assessment in comparing integration
patterns ingenuity in human target cells sampled over
three months using high-throughput pyro-sequencing. Data
will be presented. Further genotoxicity assessment will include
in vivo studies. We have established insulated vectors
which harbour both boundary and enhancer-blocking effect
and show stable in prolonged in vitro culture conditions.
Work performed with support of EC-DG research FP6-NoE,
CLINIGENE: LSHB-CT-2006-018933
Web of science
Création de la notice
15/06/2010 10:46
Dernière modification de la notice
20/08/2019 16:25
Données d'usage