A pressure-mediated nonviral method for efficient arterial gene and oligonucleotide transfer.

Journal Article

In this study, we report a method of controlled pressure-mediated delivery of "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 mm Hg. At an infusion pressure of 50 mm Hg, 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 mm Hg, 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 mm Hg, 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 mm Hg. Luciferase expression was significantly higher in pressure-transfected injured atherosclerotic arteries (5467.3+/-1047.6 fg/mg protein at 760 mm Hg). 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.

Full Text

Duke Authors

Cited Authors

  • von der Leyen, HE; Braun-Dullaeus, R; Mann, MJ; Zhang, L; Niebauer, J; Dzau, VJ

Published Date

  • September 20, 1999

Published In

Volume / Issue

  • 10 / 14

Start / End Page

  • 2355 - 2364

PubMed ID

  • 10515455

International Standard Serial Number (ISSN)

  • 1043-0342

Digital Object Identifier (DOI)

  • 10.1089/10430349950017004

Language

  • eng

Conference Location

  • United States