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Titolo:
Free cholesterol enhances adenoviral vector gene transfer and expression in CAR-deficient cells
Autore:
Worgall, S; Worgall, TS; Kostarelos, K; Singh, R; Leopold, PL; Hackett, NR; Crystal, RG;
Indirizzi:
Cornell Univ, Weill Med Coll, Div Pulm & Crit Care Med, New York, NY 10021USA Cornell Univ New York NY USA 10021 & Crit Care Med, New York, NY 10021USA Cornell Univ, Weill Med Coll, Belfer Gene Therapy Core Facil, New York, NY10021 USA Cornell Univ New York NY USA 10021 rapy Core Facil, New York, NY10021 USA Cornell Univ, Weill Med Coll, Inst Med Genet, New York, NY 10021 USA Cornell Univ New York NY USA 10021 Inst Med Genet, New York, NY 10021 USA Columbia Univ, Sch Phys & Surg, Inst Human Nutr, New York, NY 10032 USA Columbia Univ New York NY USA 10032 st Human Nutr, New York, NY 10032 USA Columbia Univ, Sch Phys & Surg, Dept Pediat, New York, NY 10032 USA Columbia Univ New York NY USA 10032 , Dept Pediat, New York, NY 10032 USA
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 1, volume: 1, anno: 2000,
pagine: 39 - 48
SICI:
1525-0016(200001)1:1<39:FCEAVG>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
IN-VITRO; CATIONIC LIPIDS; HUMAN-FIBROBLASTS; EFFICIENCY; RECEPTOR; DELIVERY; PATHWAY; LYMPHOCYTES; MACROPHAGES; ANTIBODIES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
46
Recensione:
Indirizzi per estratti:
Indirizzo: Worgall, S Cornell Univ, New York Presbyterian Hosp, Weill Med Coll, Inst Med Genet, 520 E 70th St,ST 505, New York, NY 10021 USA Cornell Univ 520 E 70th St,ST 505 New York NY USA 10021 021 USA
Citazione:
S. Worgall et al., "Free cholesterol enhances adenoviral vector gene transfer and expression in CAR-deficient cells", MOL THER, 1(1), 2000, pp. 39-48

Abstract

Efficient adenovirus vector-mediated gene transfer depends on the presenceof sufficient amounts of the high-affinity coxsackie-adenovirus (Ad) receptor (CAR) on the surface of the target cell leading to receptor-mediated endocytosis of the vector. The present study evaluates the effect of free cholesterol, a lipid component of endocytic vesicles, on Ad uptake into CAR-deficient cells. Infection in the presence of free cholesterol at its maximumsolubility in water led to increased binding, uptake, and expression of Adin human skin fibroblasts and alveolar macrophages, two primary human cells known to be deficient in CAR. The effect of free cholesterol was maximal at its solubility maximum in aqueous solution. Increase of Ad vector-mediated gene transfer with cholesterol was dependent on the lack of CAR receptorexpression on the surface and was diminished by overexpression of CAR in CAR-deficient cells. Cholesterol-mediated increase of Ad-mediated gene expression was dependent on coincubation of both cholesterol and Ad and was not dependent on the cholesterol content of the cell. Increased Ad vector-mediated gene expression in the presence of free cholesterol was also observed in murine skin in vivo. Structural analysis of the Ad-cholesterol mixture showed complexation between Ad particles leading to formation of multivirus aggregates due to hydrophobic interaction. The addition of free cholesterol with Ad vectors may be a simple way to increase Ad-mediated gene transfer to cells that are poor targets due to their lack of a sufficient number of Ad receptors.

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Documento generato il 25/09/20 alle ore 23:56:50