Stable transduction of actively dividing cells via a novel adenoviral/episomal vector

Citation
H. Leblois et al., Stable transduction of actively dividing cells via a novel adenoviral/episomal vector, MOL THER, 1(4), 2000, pp. 314-322
Citations number
25
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
MOLECULAR THERAPY
ISSN journal
1525-0016 → ACNP
Volume
1
Issue
4
Year of publication
2000
Pages
314 - 322
Database
ISI
SICI code
1525-0016(200004)1:4<314:STOADC>2.0.ZU;2-8
Abstract
Many gene therapy indications would benefit from vectors capable of achievi ng efficient in vivo delivery and long-term transgene expression in either dividing or nondividing cells. Such vector systems are not yet available. T o achieve both goals, we have used noncytotoxic E1- and E4-deleted adenovir al vectors as vehicles for delivering an Epstein-Barr virus-based self-repl icating episome (replicon) via Cre/loxP site-specific recombination. Go-inf ection of human cells with a proreplicon-encoded and a Cre-expressing adeno virus resulted in efficient delivery and excision of a functional replicon in the absence of vector-induced cytotoxicity. In addition, replication and nuclear retention of the replicon in the cell progeny translated into a pr olonged transgene expression in actively dividing cells, both in vitro and in vivo. Combining desired features from different viruses within a single hybrid vector system should expand the range of clinical indications curren tly amenable to gene transfer.