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Titolo:
Targeting transgene expression for cystic fibrosis gene therapy
Autore:
Koehler, DR; Hannam, V; Belcastro, R; Steer, B; Wen, YX; Post, M; Downey, G; Tanswell, AK; Hu, J;
Indirizzi:
Hosp Sick Children, Programme Lung Biol Res, Toronto, ON M5G 1X8, Canada Hosp Sick Children Toronto ON Canada M5G 1X8 Toronto, ON M5G 1X8, Canada Hosp Sick Children, Canadian Inst Hlth Res Grp Lung Dev, Toronto, ON M5G 1X8, Canada Hosp Sick Children Toronto ON Canada M5G 1X8 Toronto, ON M5G 1X8, Canada Univ Toronto, Dept Paediat, Toronto, ON, Canada Univ Toronto Toronto ON Canada oronto, Dept Paediat, Toronto, ON, Canada Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada Univ Toronto Toronto ON Canada Lab Med & Pathobiol, Toronto, ON, Canada Univ Toronto, Div Resp, Toronto, ON, Canada Univ Toronto Toronto ON Canada iv Toronto, Div Resp, Toronto, ON, Canada Toronto Gen Hosp, Inst Res, Toronto, ON, Canada Toronto Gen Hosp Toronto ON Canada n Hosp, Inst Res, Toronto, ON, Canada
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 1, volume: 4, anno: 2001,
pagine: 58 - 65
SICI:
1525-0016(200107)4:1<58:TTEFCF>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
DNA LPD COMPLEXES; IN-VIVO; SUBMUCOSAL GLANDS; CFTR EXPRESSION; INTERFERON-GAMMA; LUNG; MICE; PROMOTER; DELIVERY; TRANSFECTION;
Keywords:
cystic fibrosis; cytokeratin 18; DODAC : DOPE; systemic gene therapy;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
49
Recensione:
Indirizzi per estratti:
Indirizzo: Hu, J Hosp Sick Children, Programme Lung Biol Res, 555 Univ Ave, Toronto, ON M5G1X8, Canada Hosp Sick Children 555 Univ Ave Toronto ON Canada M5G 1X8X8, Canada
Citazione:
D.R. Koehler et al., "Targeting transgene expression for cystic fibrosis gene therapy", MOL THER, 4(1), 2001, pp. 58-65

Abstract

We have developed an expression cassette for cystic fibrosis (CF) gene therapy using control elements from the human cytokeratin 18 gene (KRT18, alsoknown as K18). KRT18 is naturally expressed in a spatial pattern similar to that of CFTR, the gene mutated in CF. We delivered a KRT18-driven lad. plasmid complexed with cationic liposomes intravenously to mice and examined expression in various tissues. We found expression in nasal and bronchial epithelium, airway submucosal glands, gall bladder, and kidneys. Expression was low in pancreas and gut, and absent from liver and alveolar lung. This is consistent with the expression pattern reported for a K18lacZ transgenicmoose. Following delivery of a cytomegalovirus (CMV) major immediate-earlypromoter/enhancer-driven lacZ plasmid, we found expression in bronchi, submucosal glands, alveolar cells, liver, and kidney. We did not detect expression in nose, pancreas, gall bladder, or gut. Using fluorescently labeled plasmid delivered by means of liposomes, we identified the liver, alveolar lung, and kidneys as the major plasmid deposition sites. Our data demonstrate that a KRT18-driven expression vector delivered systemically can target gene expression to CF-affected tissues, despite an uneven distribution of plasmid DNA. A KRT18-based vector may be a useful alternative to viral promoter-based vectors in clinical gene therapy trials to treat CF.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 13/07/20 alle ore 20:29:03