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Titolo:
Reducing the native tropism of adenovirus vectors requires removal of bothCAR and integrin interactions
Autore:
Einfeld, DA; Schroeder, R; Roelvink, PW; Lizonova, A; King, CR; Kovesdi, I; Wickham, TJ;
Indirizzi:
GenVec Inc, Gaithersburg, MD 20878 USA GenVec Inc Gaithersburg MD USA 20878 nVec Inc, Gaithersburg, MD 20878 USA
Titolo Testata:
JOURNAL OF VIROLOGY
fascicolo: 23, volume: 75, anno: 2001,
pagine: 11284 - 11291
SICI:
0022-538X(200112)75:23<11284:RTNTOA>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
MEDIATED GENE-TRANSFER; PENTON BASE; AIRWAY EPITHELIA; FIBER PROTEINS; SUBGROUP-C; RECEPTOR; EXPRESSION; DELIVERY; ATTACHMENT; ENTRY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
33
Recensione:
Indirizzi per estratti:
Indirizzo: Einfeld, DA GenVec Inc, 65 W Watkins Mill Rd, Gaithersburg, MD 20878 USA GenVec Inc 65 W Watkins Mill Rd Gaithersburg MD USA 20878 USA
Citazione:
D.A. Einfeld et al., "Reducing the native tropism of adenovirus vectors requires removal of bothCAR and integrin interactions", J VIROLOGY, 75(23), 2001, pp. 11284-11291

Abstract

The development of tissue-selective virus-based vectors requires a better understanding of the role of receptors in gene transfer in vivo, both to rid the vectors of their native tropism and to introduce new specificity. CARand alphav integrins have been identified as the primary cell surface components that interact with adenovirus type 5 (Ad5)-based vectors during in vitro transduction. We have constructed a set of four vectors, which individually retain the wild-type cell interactions, lack CAR binding, lack alphavintegrin binding, or lack both CAR and alphav integrin binding. These vectors have been used to examine the roles of CAR and av integrin in determining the tropism of Ad vectors in a mouse model following intrajugular or intramuscular injection. CAR was found to play a significant role in liver transduction. The absence of CAR binding alone, however, had little effect on the low level of expression from Ad in other tissues. Binding of alphav integrins appeared to have more influence than did binding of CAR in promotingthe expression in these tissues and was also found to be important in liver transduction by Ad vectors. An effect of the penton base modification wasa reduction in the number of vector genomes that could be detected in several tissues. In the liver, where CAR binding is important, combining defects in CAR and alphav integrin binding was essential to effectively reduce the high level of expression from Ad vectors. While there may be differences in Ad vector tropism among species, our results indicate that both CAR and av integrins can impact vector distribution in vivo. Disruption of both CARand av integrin Interactions may be critical for effectively reducing native tropism and enhancing the efficacy of specific targeting ligands in redirecting Ad vectors to target tissues.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 12/07/20 alle ore 06:36:34