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Titolo:
Specific depletion of human anti-adenovirus antibodies facilitates transduction in an in vivo model for systemic gene therapy
Autore:
Rahman, A; Tsai, V; Goudreau, A; Shinoda, JY; Wen, SF; Ramachandra, M; Ralston, R; Maneval, D; LaFace, D; Shabram, P;
Indirizzi:
Canji Inc, Dept Mol Biol, San Diego, CA 92121 USA Canji Inc San Diego CA USA 92121 , Dept Mol Biol, San Diego, CA 92121 USA Canji Inc, Dept Pharmacol, San Diego, CA 92121 USA Canji Inc San Diego CAUSA 92121 Dept Pharmacol, San Diego, CA 92121 USA Canji Inc, Dept Proc Sci, San Diego, CA 92121 USA Canji Inc San Diego CA USA 92121 , Dept Proc Sci, San Diego, CA 92121 USA
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 5, volume: 3, anno: 2001,
parte:, 1
pagine: 768 - 778
SICI:
1525-0016(200105)3:5<768:SDOHAA>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
CELLULAR IMMUNE-RESPONSES; CONDUCTANCE REGULATOR GENE; ENCODING HUMAN P53; I CLINICAL-TRIAL; RECOMBINANT ADENOVIRUS; PHASE-I; MOUSE-LIVER; NEUTRALIZING ANTIBODY; TRANSGENE EXPRESSION; LUNG-CANCER;
Keywords:
recombinant adenovirus; neutralizing antibodies; capsid columns; immunopheresis; transduction efficiency; beta-galactosidase rAd-vector; empty rAd-vector; green fluorescent protein rAd-vector; depletion;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
51
Recensione:
Indirizzi per estratti:
Indirizzo: Shabram, P Canji Inc, Dept Mol Biol, 3525 John Hopkins Court, San Diego, CA 92121 USA Canji Inc 3525 John Hopkins Court San Diego CA USA 92121 21 USA
Citazione:
A. Rahman et al., "Specific depletion of human anti-adenovirus antibodies facilitates transduction in an in vivo model for systemic gene therapy", MOL THER, 3(5), 2001, pp. 768-778

Abstract

Recombinant adenoviral (rAd) vectors are capable of mediating high-efficiency gene transfer in vivo. Under conditions requiring systemic administration, however, the use of rAd vectors can be problematic due to the presence of circulating anti-adenovirus antibodies developed either through natural infection or during the course of treatment. We developed a passive immunization model in SCID/Beige mice to assess the effect of human and mouse anti-adenovirus antibodies on systemic administration of a rAd vector expressing beta -galactosidase (rAd-beta gal). In this model, the in vitro neutralizing activity of human or mouse antibodies used for passive immunization correlated well with inhibition of transduction of the liver following i.v. administration of rAd-beta gal. Depletion of antibodies to individual adenovirus structural proteins (hexon, penton, fiber) by affinity chromatography demonstrated that antibodies to each of the three virion components contributed to neutralization of infectivity in vitro and to inhibition of transduction in vivo. Depletion of antibodies against all three structural proteinsfrom human or mouse immune serum prior to passive immunization restored invivo transduction activity to levels comparable to those obtained with nonimmune serum. Our data suggest that depletion of both murine and human anti-adenoviral antibodies can restore transduction in vivo during systemic rAdgene therapy in hosts previously exposed to adenovirus.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 12/07/20 alle ore 06:33:55