In VivoGene Delivery via Portal Vein and Bile Duct to Individual Lobes of the Rat Liver Using a Polylysine-Based Nonviral DNA Vector in Combination with Chloroquine

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Abstract
The objective of this study was to evaluate a bifunctional synthetic peptide as a DNA vector for regional gene delivery to the rat liver by the portal vein and bile duct routes. The 31-amino-acid peptide (polylysine-molossin) comprises an amino-terminal chain of 16 lysines for electrostatic binding of DNA, and the 15 amino acid integrin-binding domain of the venom of the American pit viper, Crotalus molossus molossus. Initial in vitro evaluation demonstrated that polylysine-molossin/DNA complexes were much smaller (~50-100nm versus 500-1300nm), more positively charged, and more stable in isotonic dextrose in comparisons with salt-containing solutions. However, polylysine-molossin/DNA complexes in any solution other than complete culture medium were ineffective for gene delivery in vitro. Vector localization studies demonstrated that both the portal vein and bile duct routes provided excellent access of polylysine-molossin/DNA complexes to the liver. However, complexes delivered by the portal vein were rapidly lost (10-fold) when delivered by the bile duct route with all isotonic solutions evaluated, and that polylysine-molossin/DNA complexes in isotonic dextrose are much more effective (>10-fold) than complexes in salt-containing solutions.