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Titolo:
A pressure-mediated nonviral method for efficient arterial gene and oligonucleotide transfer
Autore:
von der Leyen, HE; Braun-Dullaeus, R; Mann, MJ; Zhang, LN; Niebauer, J; Dzau, VJ;
Indirizzi:
Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA Harvard Univ BostonMA USA 02115 Sch Med, Dept Med, Boston, MA 02115 USA Brigham & Womens Hosp, Boston, MA 02115 USA Brigham & Womens Hosp Boston MA USA 02115 mens Hosp, Boston, MA 02115 USA Stanford Univ, Sch Med, Falk Cardiovasc Res Ctr, Div Cardiovasc Med, Stanford, CA 94305 USA Stanford Univ Stanford CA USA 94305 ardiovasc Med, Stanford, CA 94305 USA
Titolo Testata:
HUMAN GENE THERAPY
fascicolo: 14, volume: 10, anno: 1999,
pagine: 2355 - 2364
SICI:
1043-0342(19990920)10:14<2355:APNMFE>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
RECOMBINANT ADENOVIRUS; EXPRESSION INVIVO; ENDOTHELIAL-CELLS; VASCULAR INJURY; RABBIT MODEL; PLASMID DNA; WALL; THERAPY; CATHETER; HYPERPLASIA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Dzau, VJ Harvard Univ, Sch Med, Dept Med, 75 Francis St, Boston, MA 02115 USA Harvard Univ 75 Francis St Boston MA USA 02115 ston, MA 02115 USA
Citazione:
H.E. von der Leyen et al., "A pressure-mediated nonviral method for efficient arterial gene and oligonucleotide transfer", HUM GENE TH, 10(14), 1999, pp. 2355-2364

Abstract

In this study, we report a method of controlled pressure-mediated deliveryof "naked" DNA that achieves efficient and safe arterial gene and oligonucleotide transfer. We demonstrated a pressure-dependent uptake of fluorescein-labeled (FITC) oligonucleotide (ODN) in rabbit carotid arteries with preexisting neointimal hyperplasia, using nondistending intravascular delivery pressures ranging from 0 to 760 mmHg. At an infusion pressure of 50 mmHg, 10.5 +/- 5% of neointimal cell nuclei were positive for nuclear uptake of FITC-ODN 4 days after transfection, With an infusion pressure of 760 mmHg, the transfection efficiency increased to 84.2 +/- 5.3% of neointimal cells, and to 64.5 +/- 11.6 and 92.4 +/- 5.5% of medial and adventitial cells, respectively. Similar patterns of FITC-ODN uptake were seen in atherosclerotic injured arteries. We also investigated the pressure-mediated delivery of plasmid DNA. Transfection of a luciferase expression plasmid, using an infusion pressure of 760 mmHg, yielded luciferase expression of 816.6 +/- 108.6 fg/mg protein in normal rabbit carotid arteries, as compared with 38.9 +/- 23.7 fg/mg protein at 100 mmHg. Luciferase expression was significantily higher in pressure-transfected injured atherosclerotic arteries (5467.3 +/- 1047.6 fg/mg protein at 760 mmHg). Transfection of beta-galactosidase indicated that significant transgene expression occurred in the neointima and media. These data indicate that this pressure-mediated transfection method yields efficient oligonucleotide delivery and enhances transduction with plasmid DNA in normal as well as injured nonatherosclerotic or atherosclerotic arteries.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/09/20 alle ore 11:40:37