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Augmentation of myocardial transfection using TerplexDNA: a novel gene delivery system
Journal article   Open access   Peer reviewed

Augmentation of myocardial transfection using TerplexDNA: a novel gene delivery system

D G Affleck, L Yu, D A Bull, S H Bailey and S W Kim
Gene therapy, v 8(5), pp 349-353
01 Mar 2001
PMID: 11313810
url
https://doi.org/10.1038/sj.gt.3301395View
Published, Version of Record (VoR) Restricted

Abstract

Animals DNA, Complementary - genetics Genes, Reporter Genetic Therapy - methods Genetic Vectors Lipoproteins, LDL - genetics Luciferases - genetics Luciferases - metabolism Male Myocardium - enzymology Polylysine - genetics Rabbits Rats Rats, Sprague-Dawley Stearates Transfection - methods
Gene therapy is a potential new strategy for the treatment of cardiovascular disease. The most efficacious method of gene delivery remains a key hurdle to effective gene therapy. We present the application of a novel, nonviral gene delivery system (TerplexDNA) to augment myocardial transfection. The hearts of New Zealand white rabbits were injected with reporter genes, luciferase cDNA or beta-galactosidase cDNA, either as naked plasmid DNA or plasmid DNA complexed with stearyl-poly(L-lysine)-low density lipoprotein (TerplexDNA). Three day left heart myocardial cell lysates produced 44571 +/- 8730 RLU (RLU = total light units/mg protein) for the TerplexDNA luciferase rabbits versus 1638 +/- 567 RLU for the naked luciferase rabbits (P = 0.002). Thirty days after injection, myocardial lysates produced 677 +/- 52 RLU for the TerplexDNA luciferase hearts versus 18 +/- 3 RLU for the naked luciferase hearts (P = 0.002). Histologic analysis of the hearts transfected with beta-galactosidase showed that TerplexDNA increased the area and depth of transfection compared with the naked plasmid DNA alone. The hearts of Sprague-Dawley rats were injected in a similar fashion and analyzed at 1, 3, 5, 10, 15, 25 and 30 days after injection. The naked luciferase injected hearts showed transient elevation of luciferase activity to day 5 but fell back to baseline levels after that time-point. The TerplexDNA luciferase injected hearts had significantly elevated luciferase activity to 30 days. The Terplex gene delivery system significantly augments myocardial transfection compared with a naked plasmid DNA system alone. The advantage in transfection efficiency appears to be related to the unique properties of the TerplexDNA carrier molecule. The TerplexDNA delivery system represents a novel means to augment transfection of the myocardium.

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Web of Science research areas
Biochemistry & Molecular Biology
Biotechnology & Applied Microbiology
Genetics & Heredity
Medicine, Research & Experimental
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