Characterization of insulators and barrier elements for gene therapy

Détails

ID Serval
serval:BIB_86FC6084DC0C
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
Abstract (résumé de présentation): article court qui reprend les éléments essentiels présentés à l'occasion d'une conférence scientifique dans un poster ou lors d'une intervention orale.
Collection
Publications
Titre
Characterization of insulators and barrier elements for gene therapy
Titre de la conférence
SFTCG 2009 Invited Presentations
Auteur(s)
Mermod N.
Organisation
Abstracts 8th Annual Meeting French Society of Cell and Gene Therapy, 21-23 June 2009, Faculté de Médecine de la Pitié-Salpêtrière, Paris, France
ISBN
1043-0342
Statut éditorial
Publié
Date de publication
2009
Peer-reviewed
Oui
Volume
20
Série
Human Gene Therapy
Pages
658-658
Langue
anglais
Notes
8th Annual Meeting of the French-Society-of-Cell-and-Gene-Therapy Paris, FRANCE, JUN 21-23, 2009 French Soc Cell & Gene Therapy
Résumé
Gene transfer that relies on integrating vectors often suffers
from epigenetic or regulatory effects that influence the expression
of the therapeutic gene and=or of cellular genes located
near the vector integration site in the chromosome.
Insulator elements act to block gene activation by enhancers,
while chromatin domain boundary or barrier sequences
prevent gene-silencing effects. At present, the modes of action
of insulator and barriers are poorly understood, and their use
in the context of gene therapies remains to be documented.
Using combinations of reporter genes coding for indicator
fluorescent proteins, we constructed assay systems that allow
the quantification of the insulator or barrier activities of genetic
elements in individual cells. This presentation will illustrate
how these assay systems were used to identify short
DNA elements that insulate nearby genes from activation by
viral vector elements, and=or that block the propagation of a
silent chromatin structure that leads to gene silencing. We
will show that some barrier elements do not merely block
repressive effects, but that they can act to stabilize and sustain
transgene expression. We will illustrate that this may be
beneficial when transgenes are introduced into stem or precursor
cells using non-viral vectors, where later differentiation
may lead to the silencing of the therapeutic gene. We will
show that these elements can be used to maintain efficient
transgene expression upon the differentiation of murine
precursor cells towards myofibers, in a model of cell therapy
for muscle dystrophies.
Création de la notice
15/06/2010 11:55
Dernière modification de la notice
03/03/2018 19:00
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