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Titolo:
Slow accumulation of plasmid in muscle cells: Supporting evidence for a mechanism of DNA uptake by receptor-mediated endocytosis
Autore:
Satkauskas, S; Bureau, MF; Mahfoudi, A; Mir, LM;
Indirizzi:
Inst Gustave Roussy, UMR 8532 CNRS, LPPMB, F-94805 Villejuif, France Inst Gustave Roussy Villejuif France F-94805 , F-94805 Villejuif, France Vytautas Magnus Univ, Dept Biol, LT-3000 Kaunas, Lithuania Vytautas MagnusUniv Kaunas Lithuania LT-3000 LT-3000 Kaunas, Lithuania Aventis, ENSCP, UMR 7001 CNRS, F-94403 Vitry Sur Seine, France Aventis Vitry Sur Seine France F-94403 , F-94403 Vitry Sur Seine, France
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 4, volume: 4, anno: 2001,
pagine: 317 - 323
SICI:
1525-0016(200110)4:4<317:SAOPIM>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
DIRECT GENE-TRANSFER; MOUSE SKELETAL-MUSCLE; IN-VIVO; EXPRESSION; INJECTION; PROTEIN; BLEOMYCIN; BINDING; THERAPY; INVIVO;
Keywords:
gene therapy; DNA electrotransfer; electrogene therapy; muscle; naked DNA; plasmid DNA; kinetics; in vivo; heparin; receptor-mediated endocytosis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
33
Recensione:
Indirizzi per estratti:
Indirizzo: Mir, LM Inst Gustave Roussy, UMR 8532 CNRS, LPPMB, Rue Camille Desmoulins,F-94805Villejuif, France Inst Gustave Roussy Rue Camille Desmoulins Villejuif France F-94805
Citazione:
S. Satkauskas et al., "Slow accumulation of plasmid in muscle cells: Supporting evidence for a mechanism of DNA uptake by receptor-mediated endocytosis", MOL THER, 4(4), 2001, pp. 317-323

Abstract

Intramuscular plasmid DNA injection results in long-term but low and variable expression of the injected genes. Optimization is difficult because themechanism of naked DNA uptake by the cells in vivo is not yet determined. Here we used injections of plasmid DNA encoding luciferase to further characterize this mechanism. We analyzed the kinetics of naked DNA uptake by means of DNase I or heparin injections, using the level of luciferase expression as the indicator of DNA uptake. We demonstrated that in vivo heparin inhibits DNA uptake without affecting the expression of DNA internalized by means of electric pulses. Inhibition by heparin is dose dependent and compatible with the competition for the binding to a receptor. As shown also with DNase 1, DNA uptake by muscle cells is slow: a progressive accumulation of the DNA in the myofibers can be found for at least 4 hours after naked DNA injection. Physical presence of DNA molecules during the uptake period, butnot later, was confirmed by the facilitation of DNA uptake with appropriate electric pulses. Therefore, uptake proceeds for the entire time during which intact DNA is present in the extracellular compartment. Our results support evidence for a DNA uptake mechanism based on receptor- mediated endocytosis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/02/20 alle ore 12:48:28