Poly-L-lysine improves gene transfer with adenovirus formulated in PLGA microspheres.
In vivo gene transfer with recombinant adenovirus vectors can be hindered by the immunogenicity of the adenovirus capsid proteins. Previous work showed that formulation of the vector with biodegradable polymers such as poly-lactic-glycolic acid (PLGA), polyethylene glycol (PEG), or lipids, may shield the virus from inhibition by neutralizing antibodies. Formulation of adenovirus in PLGA microspheres also allowed for extended release in vitro. In experiments described here, we found that the surfactant used in the formation of the primary emulsion could significantly improve the overall yield of virus released. We also tested the effects of adding poly-L-lysine to adenovirus before encapsulation with PLGA. Our results show that although PLL did not effect the yield of virus encapsulated or released from the microspheres, it significantly improved the efficiency of gene transfer after release from the polymer.
Matthews
C
C
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, IA 52242, USA.
Jenkins
G
G
Hilfinger
J
J
Davidson
B
B
D000256:Adenoviridae / Q000235:genetics*; D001672:Biocompatible Materials; D002853:Chromatography, Liquid; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage*; D006367:HeLa Cells; D006801:Humans; D019344:Lactic Acid; D013058:Mass Spectrometry; D008863:Microspheres; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011107:Polylysine; D011108:Polymers; D001616:beta-Galactosidase / Q000235:genetics
D001672:Biocompatible Materials; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011107:Polylysine; D011100:Polyglycolic Acid; D019344:Lactic Acid; D001616:beta-Galactosidase