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Titolo:
Efficient and selective AAV2-mediated gene transfer directed to human vascular endothelial cells
Autore:
Nicklin, SA; Buening, H; Dishart, KL; de Alwis, M; Girod, A; Hacker, U; Thrasher, AJ; Ali, RR; Hallek, M; Baker, AH;
Indirizzi:
Univ Glasgow, Dept Med & Therapeut, Glasgow G11 6NT, Lanark, Scotland UnivGlasgow Glasgow Lanark Scotland G11 6NT ow G11 6NT, Lanark, Scotland Univ Munich, Genzentrum, Mol Biol Lab, D-81377 Munich, Germany Univ Munich Munich Germany D-81377 Mol Biol Lab, D-81377 Munich, Germany Univ Coll London, Inst Child Hlth, London, England Univ Coll London London England ondon, Inst Child Hlth, London, England
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 3, volume: 4, anno: 2001,
pagine: 174 - 181
SICI:
1525-0016(200109)4:3<174:EASAGT>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
ADENOASSOCIATED VIRUS VECTORS; SMOOTH-MUSCLE CELLS; COAGULATION FACTOR-IX; VIRAL VECTOR; HEMOPHILIA-B; MOUSE-LIVER; TYPE-2; ADENOVIRUS; DELIVERY; EXPRESSION;
Keywords:
AAV; retargeting; vascular endothelial cells; peptides; phage display; gene therapy; gene transfer;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
50
Recensione:
Indirizzi per estratti:
Indirizzo: Baker, AH Univ Glasgow, Dept Med & Therapeut, Glasgow G11 6NT, Lanark, Scotland Univ Glasgow Glasgow Lanark Scotland G11 6NT , Lanark, Scotland
Citazione:
S.A. Nicklin et al., "Efficient and selective AAV2-mediated gene transfer directed to human vascular endothelial cells", MOL THER, 4(3), 2001, pp. 174-181

Abstract

Gene therapy vectors based on adeno-associated virus-2 (AAV2) offer considerable promise for human gene therapy. Applications for AAV vectors are limited to tissues efficiently transduced by the vector due to its natural tropism, which is predominantly skeletal muscle, neurons, and hepatocytes. Tropism modification to elevate efficiency and/or selectivity to individual cell types would enhance the scope of AAV for disease therapies. The vascularendothelium is implicitly important in cardiovascular diseases and cancer,but is relatively poorly transduced by AAV vectors. We therefore genetically incorporated the peptide SIGYPLP, which targets endothelial cells (EC), into position I-587 of AAV capsids. SIGYPLP-modified AAV (AAVsig) showed enhanced transduction of human EC compared with AAV with a wild-type capsid (AAVwt), a phenotype independent of heparan sulphate proteoglycan (HSPG) binding. In contrast, AAVsig did not enhance transduction of primary human vascular smooth muscle cells or human hepatocytes, principal targets for AAV vectors in local or systemic gene delivery applications, respectively. Furthermore, infection of EC in the presence of bafilomycin A(2) indicated that intracellular trafficking of AAV particles was altered by targeting AAV by means of SIGYPLP. AAV vectors with enhanced tropism for EC will be useful for diverse gene therapeutics targeted at the vasculature.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 18/02/20 alle ore 05:29:38