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Titolo:
GRADIENT OF RGD-DEPENDENT ENTRY OF ADENOVIRAL VECTOR IN NASAL AND INTRAPULMONARY EPITHELIA - IMPLICATIONS FOR GENE-THERAPY OF CYSTIC-FIBROSIS
Autore:
GOLDMAN M; SU Q; WILSON JM;
Indirizzi:
UNIV PENN,WISTAR INST,INST HUMAN GENE THERAPY,3601 SPRUCE ST,RM 204 PHILADELPHIA PA 19104 UNIV PENN,WISTAR INST,INST HUMAN GENE THERAPY PHILADELPHIA PA 19104 UNIV PENN,DEPT MED PHILADELPHIA PA 19104 UNIV PENN,DEPT MOL & CELLULAR ENGN PHILADELPHIA PA 19104
Titolo Testata:
Gene therapy
fascicolo: 9, volume: 3, anno: 1996,
pagine: 811 - 818
SICI:
0969-7128(1996)3:9<811:GOREOA>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
CELL-ADHESION RECEPTORS; HUMAN CFTR CDNA; MEDIATED TRANSFER; IN-VIVO; AIRWAY EPITHELIUM; INTEGRIN; LUNG; INDIVIDUALS; EFFICACY; PRIMATES;
Keywords:
THERAPY; CYSTIC FIBROSIS; ADENOVIRAL VECTORS; ALPHA(V)BETA INTEGRINS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
29
Recensione:
Indirizzi per estratti:
Citazione:
M. Goldman et al., "GRADIENT OF RGD-DEPENDENT ENTRY OF ADENOVIRAL VECTOR IN NASAL AND INTRAPULMONARY EPITHELIA - IMPLICATIONS FOR GENE-THERAPY OF CYSTIC-FIBROSIS", Gene therapy, 3(9), 1996, pp. 811-818

Abstract

The efficiency with which adenoviral vectors infect airway epithelialcells in vivo is unclear despite extensive preclinical and clinical studies. Our hypothesis is that gene transfer is limited by vector internalization which is mediated by binding of a fiber with a cellular receptor and the RGD motif of the penton base of the virus with cellularalpha(v) beta integrin. Experiments in mice demonstrate an anatomicalgradient of susceptibility to adenoviral vector-mediated gene transfer with epithelia of proximal structures such as nose and trachea, muchless infectable than the distal noncartilaginous airway. Throughout the airway, gene transfer is dependent on RGD-mediated interactions which are rate limiting in the distal lung. A panel of tissues from cystic fibrosis and non-cystic fibrosis patients was analyzed for expression of alpha(v) beta(5) integrin which is capable of mediating ROD-dependent uptake of vector Luminal epithelial cells of the nose and tracheawere void of alpha(v) beta(5) expression whereas abundant expression of this integrin was present in virtually all epithelial cells of distal conducting airway These findings could explain difficulties we and others have had in correcting the functional deficit of cystic fibrosis nasal epithelia and suggest that gene transfer efficiency may be greater in distal human lung.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/07/20 alle ore 21:33:42