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Titolo:
TRANSCRIPTIONAL TARGETING OF REPLICATION-DEFECTIVE ADENOVIRUS TRANSGENE EXPRESSION TO SMOOTH-MUSCLE CELLS IN-VIVO
Autore:
KIM S; LIN H; BARR E; CHU L; LEIDEN JM; PARMACEK MS;
Indirizzi:
UNIV CHICAGO,DEPT MED,ROOM G611,MC 6088,5841 S MARYLAND AVE CHICAGO IL 60637 UNIV CHICAGO,DEPT MED CHICAGO IL 60637 UNIV CHICAGO,DEPT PATHOL CHICAGO IL 60637
Titolo Testata:
The Journal of clinical investigation
fascicolo: 5, volume: 100, anno: 1997,
pagine: 1006 - 1014
SICI:
0021-9738(1997)100:5<1006:TTORAT>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
DEPENDENT KINASE INHIBITOR; RAT CAROTID-ARTERY; GENE-THERAPY; IN-VIVO; RECOMBINANT ADENOVIRUS; BALLOON ANGIOPLASTY; INTIMAL HYPERPLASIA; NEOINTIMA FORMATION; MEDIATED TRANSFER; PORCINE ARTERIES;
Keywords:
SMOOTH MUSCLE; ADENOVIRUS; GENE THERAPY; ATHEROSCLEROSIS; VASCULAR DISEASES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
44
Recensione:
Indirizzi per estratti:
Citazione:
S. Kim et al., "TRANSCRIPTIONAL TARGETING OF REPLICATION-DEFECTIVE ADENOVIRUS TRANSGENE EXPRESSION TO SMOOTH-MUSCLE CELLS IN-VIVO", The Journal of clinical investigation, 100(5), 1997, pp. 1006-1014

Abstract

Gene transfer using replication-defective adenoviruses (RDAd) holds promise for the treatment of vascular proliferative disorders, but is potentially limited by the capacity of these viruses to infect multiplecell lineages, We have generated an RDAd vector, designated AdSM22-lacZ, which encodes the bacterial lacZ reporter gene under the transcriptional control of the smooth muscle cell (SMC)-specific SM22 alpha promoter, Here, we show that in vitro AdSM22-lacZ programs expression of the lacZ reporter gene in primary rat aortic SMCs and immortalized A7r5 SMCs, but not in primary human umbilical vein endothelial cells (HUVECs) or NIH 3T3 cells, Consistent with these results, after intraarterial administration of AdSM22-lacZ to control and balloon-injured rat carotid arteries, beta-galactosidase activity was detected within SMCs of the tunica media and neointima, but not within endothelial or adventitial cells. Moreover, intravenous administration of AdSM22-lacZ did not result in lacZ gene expression in the liver or lungs, Finally, we have shown that direct injection of AdSM22-lacZ into SMC-containing tissues such as the ureter and bladder results in high-level transgene expression in visceral SMCs, Taken together, these results demonstrate that transgene expression after infection with an RDAd vector can be regulated in an SMC lineage-restricted fashion by using a transcriptional cassette containing the SMC-specific SM22 alpha promoter, The demonstration of an efficient gene delivery system targeted specifically toSMCs provides a novel means to restrict expression of recombinant gene products to vascular or visceral SMCs in vivo.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/09/20 alle ore 09:19:26