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Titolo:
Recombinant AAV-mediated delivery of a tet-inducible reporter gene to the rat retina
Autore:
Sanftner, LHM; Rendahl, KG; Quiroz, D; Coyne, M; Ladner, M; Manning, WC; Flannery, JG;
Indirizzi:
Univ Calif Berkeley, Dept Vis Sci, Berkeley, CA 94720 USA Univ Calif Berkeley Berkeley CA USA 94720 Vis Sci, Berkeley, CA 94720 USA Univ Calif Berkeley, Neurosci Grp, Berkeley, CA 94720 USA Univ Calif Berkeley Berkeley CA USA 94720 sci Grp, Berkeley, CA 94720 USA Chiron Corp, Emeryville, CA 94608 USA Chiron Corp Emeryville CA USA 94608Chiron Corp, Emeryville, CA 94608 USA
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 5, volume: 3, anno: 2001,
parte:, 1
pagine: 688 - 696
SICI:
1525-0016(200105)3:5<688:RADOAT>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
EXPRESSION IN-VIVO; ADENOASSOCIATED VIRUS VECTORS; LONG-TERM CORRECTION; MAMMALIAN-CELLS; HEMOPHILIA-B; MODEL; TRANSDUCTION; DEGENERATION; RESCUE; RETINOPATHY;
Keywords:
rAAV vector; gene therapy; retinal degeneration; tet-inducible transgene;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Flannery, JG Univ Calif Berkeley, Dept Vis Sci, 596 Minor Hall, Berkeley, CA 94720 USA Univ Calif Berkeley 596 Minor Hall Berkeley CA USA 94720 USA
Citazione:
L.H.M. Sanftner et al., "Recombinant AAV-mediated delivery of a tet-inducible reporter gene to the rat retina", MOL THER, 3(5), 2001, pp. 688-696

Abstract

Viral delivery of neurotrophins or other therapeutic genes is an attractive option for treating retinal degeneration. Regulated expression of these genes in the retina is needed to aid in dose delivery and to promote safety. To evaluate whether tetracycline (tet)-inducible transgenes encapsidated in recombinant adeno-associated viruses (rAAV) can provide controlled gene expression in vitro and in the rat retina, two viruses were constructed: a silencer/activator vector and an inducible doxycycline (dox)-responsive GFP vector. Combinations of these two viruses were subretinally injected into wild-type rats and dox was orally administered through the drinking water. Retinal GFP expression was monitored in vivo with a noninvasive fluorescenceimaging method. Eyes were also examined by histology, Western analysis, and electroretinography. Subretinal injection of rAAV efficiently delivers inducible genes to both photoreceptors and retinal pigment epithelial cells. GFP expression was initially observed 1 week postinduction, and GFP proteinwas undetectable after removal of dox. In uninduced animals, GFP expression was negligible. The dox dosage was varied in vivo and showed a correlation to the level of GFP expression. Thus, transduction of retinal cells with tet-inducible vectors allows for tight regulation of gene expression.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/01/20 alle ore 18:48:24