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Titolo:
INCREASED IN-VITRO AND IN-VIVO GENE-TRANSFER BY ADENOVIRUS VECTORS CONTAINING CHIMERIC FIBER PROTEINS
Autore:
WICKHAM TJ; TZENG E; SHEARS LL; ROELVINK PW; LI Y; LEE GM; BROUGH DE; LIZONOVA A; KOVESDI I;
Indirizzi:
GENVEC INC,12111 PARKLAWN DR ROCKVILLE MD 20852 UNIV PITTSBURGH,PRESBYTERIAN UNIV HOSP,DEPT SURG PITTSBURGH PA 15213
Titolo Testata:
Journal of virology
fascicolo: 11, volume: 71, anno: 1997,
pagine: 8221 - 8229
SICI:
0022-538X(1997)71:11<8221:IIAIGB>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
AMINO-ACID-SEQUENCE; RECOMBINANT ADENOVIRUS; CORONARY RESTENOSIS; CYSTIC-FIBROSIS; PENTON BASE; CELLS; INTEGRINS; RECEPTOR; ATTACHMENT; DELIVERY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
49
Recensione:
Indirizzi per estratti:
Citazione:
T.J. Wickham et al., "INCREASED IN-VITRO AND IN-VIVO GENE-TRANSFER BY ADENOVIRUS VECTORS CONTAINING CHIMERIC FIBER PROTEINS", Journal of virology, 71(11), 1997, pp. 8221-8229

Abstract

Alteration of the natural tropism of adenovirus (Ad) will permit genetransfer into specific cell types and thereby greatly broaden the scope of target diseases that can be treated by using Ad. We have constructed two Ad vectors which contain modifications to the Ad fiber coat protein that redirect virus binding to either alpha(v) integrin [AdZ.F(RGD)] or heparan sulfate [AdZ.F(pK7)] cellular receptors. These vectors were constructed by a novel method involving E4 rescue of an E4-deficient Ad with a transfer vector containing both the E4 region and the modified fiber gene. AdZ.F(RGD) increased gene delivery to endothelialand smooth muscle cells expressing a, integrins. Likewise, AdZ.F(pK7)increased transduction 5- to 500-fold in multiple cell types lacking high levels of Ad fiber receptor, including macrophage, endothelial, smooth muscle, fibroblast, and T cells. In addition, AdZ.F(pK7) significantly increased gene transfer in vivo to vascular smooth muscle cellsof the porcine iliac artery following balloon angioplasty. These vectors may therefore be useful in gene therapy for vascular restenosis orfor targeting endothelial cells in tumors. Although binding to the fiber receptor still occurs with these vectors, they demonstrate the feasibility of tissue-specific receptor targeting in cells which express low levels of Ad fiber receptor.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 12/07/20 alle ore 06:21:45