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Titolo:
A system for the propagation of adenoviral vectors with genetically modified receptor specificities
Autore:
Douglas, JT; Miller, CR; Kim, M; Dmitriev, I; Mikheeva, G; Krasnykh, V; Curiel, DT;
Indirizzi:
Univham,bama, Gene Therapy Ctr, Dept Med, Div Pulm & Crit Care Med, Birming Univ Alabama Birmingham AL USA 35294 d, Div Pulm & Crit Care Med, Birming Univ Alabama, Dept Radiat Oncol, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 diat Oncol, Birmingham, AL 35294 USA
Titolo Testata:
NATURE BIOTECHNOLOGY
fascicolo: 5, volume: 17, anno: 1999,
pagine: 470 - 475
SICI:
1087-0156(199905)17:5<470:ASFTPO>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
GROWTH-FACTOR RECEPTOR; TARGETED GENE DELIVERY; ESCHERICHIA-COLI; MODIFIED FIBERS; PENTON BASE; CELL LINE; TROPISM; VIRUS; PROTEIN; TYPE-5;
Keywords:
adenoviral vector; artificial receptor; gene therapy; targeting;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Agriculture,Biology & Environmental Sciences
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Curiel, DT Univham,bama, Gene Therapy Ctr, Dept Med, Div Pulm & Crit Care Med, Birming Univ Alabama Birmingham AL USA 35294 & Crit Care Med, Birming
Citazione:
J.T. Douglas et al., "A system for the propagation of adenoviral vectors with genetically modified receptor specificities", NAT BIOTECH, 17(5), 1999, pp. 470-475

Abstract

The development of genetically modified adenovirus (Ad) vectors with specificity for a single cell type will require both the introduction of novel tropism determinants and the ablation of endogenous tropism. Consequently, it will not be possible to exploit the native cellular entry pathway in the propagation of these targeted Ad vectors. Based on the concept that Ad enters cells by a two-step process in which a primary receptor serves as a highaffinity binding site for the Ad fiber knob, with subsequent internalization mediated by av integrins, we designed two artificial primary receptors. The extracellular domain of one of these synthetic receptors was derived from a single-chain antibody (sFv) with specificity for Ad5 knob, while the second receptor consisted of an icosapeptide identified by biopanning a phage display library against Ad5 knob. Expression of either of these artificial virus-binding receptors in fiber receptor-negative cells possessing cry integrins conferred susceptibility to Ad infection. We then created a novel mechanism for cell binding by genetically modifying both the vector and thetarget cell. In this approach, six histidine (His) residues were incorporated at the C-terminal of the Ad fiber protein. The resultant Ad vector was able to infect nonpermissive cells displaying the cognate artificial receptor, containing an anti-His sFv. This strategy, comprising a genetically engineered Ad virion and a modified cell line, should be useful in the propagation of targeted Ad vectors that lack the ability to bind the native fiber receptor.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 15/07/20 alle ore 20:50:57