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Titolo:
Sequential injection of cationic liposome and plasmid DNA effectively transfects the lung with minimal inflammatory toxicity
Autore:
Tan, YD; Liu, F; Li, ZY; Li, S; Huang, L;
Indirizzi:
Univ Pittsburgh, Sch Pharm, Ctr Pharmacogenet, Pittsburgh, PA 15213 USA Univ Pittsburgh Pittsburgh PA USA 15213 cogenet, Pittsburgh, PA 15213 USA Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15213 USA Univ Pittsburgh Pittsburgh PA USA 15213 armacol, Pittsburgh, PA 15213 USA
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 5, volume: 3, anno: 2001,
parte:, 1
pagine: 673 - 682
SICI:
1525-0016(200105)3:5<673:SIOCLA>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
INTRAVENOUS GENE DELIVERY; IN-VIVO; BACTERIAL-DNA; CPG MOTIFS; LINEAR POLYETHYLENIMINE; LPD COMPLEXES; MOUSE SERUM; EXPRESSION; INHIBITION; CELLS;
Keywords:
sequential injection; cationic liposome; gene transfer; lipoplex; systemic; inflammatory toxicity; cytokine induction; plasmid DNA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Huang, L Univ Pittsburgh, Sch Pharm, Ctr Pharmacogenet, 633 Salk Hall, Pittsburgh, PA 15213 USA Univ Pittsburgh 633 Salk Hall Pittsburgh PA USA 15213A 15213 USA
Citazione:
Y.D. Tan et al., "Sequential injection of cationic liposome and plasmid DNA effectively transfects the lung with minimal inflammatory toxicity", MOL THER, 3(5), 2001, pp. 673-682

Abstract

A major hurdle to lipoplex-based systemic gene delivery is acute inflammatory toxicity. In this study, a safe, simple, and effective alternative to lipoplex administration, specifically, sequential injection of cationic liposome and plasmid DNA, was evaluated. When plasmid DNA was injected into thetail vein of mice 2-5 min after the injection of cationic liposomes, 50-80% lower levels of proinflammatory cytokines, including TNF-alpha, IL-12, and IFN-gamma, were observed compared to lipoplex injection. The sequential injection technique yielded a two- to fivefold higher level of transgene expression in the lung and was more effective in repeated dosing than lipoplex. Other types of lipoplex-associated toxicities, such as neutropenia, lymphopenia, thrombocytopenia, and complement depletion, were also significantlyreduced with sequential injection. The reduction in cytokine release was observed with several different liposome formulations and appeared to be a general phenomenon.

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Documento generato il 22/01/20 alle ore 06:27:18