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Titolo:
CAR-dependent and CAR-independent pathways of adenovirus vector-mediated gene transfer and expression in human fibroblasts
Autore:
Hidaka, C; Milano, E; Leopold, PL; Bergelson, JM; Hackett, NR; Finberg, RW; Wickham, TJ; Kovesdi, I; Roelvink, P; Crystal, RG;
Indirizzi:
Cornellareiv, New York Presbyterian Hosp, Weill Med Coll, Div Pulm & Crit C Cornell Univ New York NY USA 10021 osp, Weill Med Coll, Div Pulm & Crit C Hosp Special Surg, Lab Soft Tissue Res, New York, NY 10021 USA Hosp Special Surg New York NY USA 10021 issue Res, New York, NY 10021 USA Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA Childrens Hosp Philadelphia Philadelphia PA USA 19104 lphia, PA 19104 USA Dana Farber Canc Inst, Div Infect Dis, Boston, MA 02115 USA Dana Farber Canc Inst Boston MA USA 02115 nfect Dis, Boston, MA 02115 USA GenVec Inc, Rockville, MD 20852 USA GenVec Inc Rockville MD USA 20852GenVec Inc, Rockville, MD 20852 USA
Titolo Testata:
JOURNAL OF CLINICAL INVESTIGATION
fascicolo: 4, volume: 103, anno: 1999,
pagine: 579 - 587
SICI:
0021-9738(199902)103:4<579:CACPOA>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
PENTON BASE PROTEIN; CELLULAR RECEPTORS; FIBER RECEPTOR; SUBGROUP-C; HIGH-LEVEL; ACIDIC PH; IN-VITRO; ALPHA-V; CELLS; INTEGRIN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
47
Recensione:
Indirizzi per estratti:
Indirizzo: Crystal, RG Cornellareiv, New York Presbyterian Hosp, Weill Med Coll, Div Pulm & Crit C Cornell Univ 520 E 70th St,ST505 New York NY USA 10021 Crit C
Citazione:
C. Hidaka et al., "CAR-dependent and CAR-independent pathways of adenovirus vector-mediated gene transfer and expression in human fibroblasts", J CLIN INV, 103(4), 1999, pp. 579-587

Abstract

Primary fibroblasts are not efficiently transduced by subgroup C adenovirus (Ad) vectors because they express low levels of the high-affinity Coxsackie virus and adenovirus receptor (CAR). In the present study, we have used primary human dermal fibroblasts as a model to explore strategies by which Ad vectors can be designed to enter cells deficient in CAR. Using an Ad vector expressing the human CAR cDNA (AdCAR) at high multiplicity of infection, primary fibroblasts were converted from being CAR deficient to CAR sufficient. Efficiency of subsequent gene transfer by standard Ad5-based vectors and Ad5-based vectors with alterations in penton and fiber was evaluated. Marked enhancement of binding and transgene expression by standard Ad5 vectors was achieved in CAR-sufficient fibroblasts. Expression by Ad Delta RGD beta gal, an Ad5-based vector lacking the arginine-glycine-aspartate (RGD) alpha(v) integrin recognition site from its penton base, was achieved in CAR-sufficient, but not CAR-deficient, cells. Fiber-altered Ad5-based Meters, including (a) AdF(pK7)beta gal (bearing seven lysines on the end of fiber) (b) AdF(RGD)beta gal (bearing a high-affinity RGD sequence on the end of fiber), and (c) AdF9sK beta gal(bearing a short fiber and Ad9 knob), demonstrated enhanced gene transfer in CAR-deficient fibroblasts, with no further enhancement in CAR-sufficient fibroblasts. Together, these observations demonstrate that CAR deficiency on Ad targets can be circumvented either by supplying CAR or by modifying the Ad fiber to bind to other cell-surface receptors.

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Documento generato il 03/07/20 alle ore 00:56:40