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Titolo:
Efficient CFTR expression from AAV vectors packaged with promoters - the second generation
Autore:
Wang, D; Fischer, H; Zhang, L; Fan, P; Ding, RX; Dong, J;
Indirizzi:
Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA Med Univ S Carolina Charleston SC USA 29425 nol, Charleston, SC 29425 USA Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA Med Univ S Carolina Charleston SC USA 29425 Med, Charleston, SC 29425 USA Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA Univ Calif San Francisco San Francisco CA USA 94143 ancisco, CA 94143 USA Childrens Hosp Oakland, Oakland, CA 94609 USA Childrens Hosp Oakland Oakland CA USA 94609 akland, Oakland, CA 94609 USA
Titolo Testata:
GENE THERAPY
fascicolo: 4, volume: 6, anno: 1999,
pagine: 667 - 675
SICI:
0969-7128(199904)6:4<667:ECEFAV>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
TRANSMEMBRANE CONDUCTANCE REGULATOR; AIRWAY EPITHELIAL-CELLS; MEDIATED GENE-TRANSFER; RECOMBINANT ADENOASSOCIATED VIRUS; CYSTIC-FIBROSIS; ADENOVIRUS VECTOR; IN-VIVO; NONHUMAN-PRIMATES; PHASE-I; LUNG;
Keywords:
CFTR; cystic fibrosis; AAV vector; gene therapy; expression;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
43
Recensione:
Indirizzi per estratti:
Indirizzo: Dong, J Medleston, Carolina, Dept Microbiol & Immunol, BSB 201,173 Ashley Ave, Char Med Univ S Carolina BSB 201,173 Ashley Ave Charleston SC USA 29425
Citazione:
D. Wang et al., "Efficient CFTR expression from AAV vectors packaged with promoters - the second generation", GENE THER, 6(4), 1999, pp. 667-675

Abstract

Gene therapy studies of cystic fibrosis (CF) have shown that AA V-based vector was efficient in transferring but not in expressing the CFTR cDNA in the target cells. The levels of CFTR gene expression were limited by the small packaging capacity of AAV because if had been difficult to package the CFTR cDNA with an efficient promoter. In the present study we have developeda new generation of AAV/CFTR vectors which contain efficient short promoters to express the CFTR gene in target cells. To do so, we reduced the size of the CFTR cDNA by determining the minimal untranslated regions required for expression of CFTR cDNA. We also identified short and efficient promoters that could be packaged with the down-sized CFTR cDNA into a novel AAV vector that had a maximal packaging capacity. Functional analyses showed that the new vectors were packaged efficiently and expressed higher levels of CFTR than a vector in which the CFTR gene was driven by the ITR sequence of AAV. Transduction of airway epithelial cells containing del 508 mutation with the new vectors demonstrated efficient expression of the wild-type CFTR and correction of the CF phenotype. In contrast, no significant CFTR expression was defected in cells infected with the Vector that express the CFTR gene from the ITR. These findings support the notion that the AAV can be developed into an efficient vector to transduce the CFTR gene and vectors expressing higher levels of CFTR from an efficient promoter should provide better efficacy for gene therapy of cystic fibrosis.

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Documento generato il 25/05/20 alle ore 04:58:12