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Titolo:
Stabilization of transgenes delivered by recombinant adenovirus vectors through extrachromosomal replication
Autore:
Krougliak, VA; Krougliak, N; Eisensmith, RC;
Indirizzi:
Mt Sinai Sch Med, Inst Gene Therapy & Mol Med, New York, NY 10029 USA Mt Sinai Sch Med New York NY USA 10029 & Mol Med, New York, NY 10029 USA Mt Sinai Sch Med, Dept Human Genet, New York, NY 10029 USA Mt Sinai Sch Med New York NY USA 10029 uman Genet, New York, NY 10029 USA
Titolo Testata:
JOURNAL OF GENE MEDICINE
fascicolo: 1, volume: 3, anno: 2001,
pagine: 51 - 58
SICI:
1099-498X(200101/02)3:1<51:SOTDBR>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
EPSTEIN-BARR-VIRUS; GENE-EXPRESSION; MAMMALIAN-CELLS; EARLY REGION-4; IN-VIVO; DNA; CAPACITY; TYPE-5; PERSISTENCE; ACTIVATION;
Keywords:
gene therapy; adenovirus; Epstein-Barr virus (EBV); vectors; episomal maintenance; replication;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
31
Recensione:
Indirizzi per estratti:
Indirizzo: Krougliak, VA Mt Sinai Sch Med, Inst Gene Therapy & Mol Med, Box 1496,1 Gustave L Levy Pl, New York, NY 10029 USA Mt Sinai Sch Med Box 1496,1 GustaveL Levy Pl New York NY USA 10029
Citazione:
V.A. Krougliak et al., "Stabilization of transgenes delivered by recombinant adenovirus vectors through extrachromosomal replication", J GENE MED, 3(1), 2001, pp. 51-58

Abstract

Background A major limitation of adenovirus-mediated gene therapy for metabolic and inherited diseases is the instability of transgene expression in vivo. This instability results, at least in part, from the inability of thevector genome to maintain the transgene through replication or integration. In this study we evaluated the possibility of stabilization of an adenovirus-delivered transgene by non-adenovirus replicative elements. Methods We have developed a novel system for the maintenance of transgenesdelivered by adenovirus vectors through extrachromosomal replication. In its initial configuration, this system combines the Epstein-Barr virus (EBV)replicative elements, a tetracycline (Tc)-inducible expression system, andthe Cre-lox recombination system in the context of a single E1/ E3/E4-deleted adenovirus vector. Induction of Cre expression initiates a Cre mediatedrecombination, resulting in the excision of a fragment of the vector genome and its circularization into an EBV-based episome. Results In vitro studies have demonstrated that excision of the circular episome can occur in a cell-free system as well as in cultured cells transfected with plasmid DNA or transduced by a virus vector carrying the episome-excising cassette. PCR studies have shown that in proliferating, nonpermissive, cultured primate cells the episome generated from the adenovirus vector is maintained much more stably than the genome of the parent vector. Thisepisome was also able to replicate in mammalian cells. Conclusion Together these studies demonstrate the feasibility of this approach for the stabilization of transgenes delivered to dividing cells by adenovirus vectors. Copyright (C) 2000 John Wiley & Sons, Ltd.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 11/07/20 alle ore 20:55:42