(69f) Surface-Mediated Gene Delivery Of Peptide-Lipoplexes

The development of safe and efficient gene delivery methods is a fundamental goal of gene therapy. Delivery of vectors from biomaterials has been employed as a means to overcome mass transport limitations, which is particularly important for lipoplexes for which cellular internalization is a rate-limiting step. In this report, we investigate the hypothesis that the incorporation of cationic peptides into lipoplexes can modulate the interactions of the vector with the substrate, and may enhance cellular binding and internalization. Peptide-lipoplexes were formed by the addition of short, cationic peptides to DNA prior to the addition of Lipofectamine. Complexes were immobilized to tissue-culture polystyrene prior to the seeding of NIH3T3 cells. Surface-mediated transfection with peptide-lipoplexes resulted in a 7.4-fold increase in transfection efficiency compared to using lipids alone. In addition, the amount of peptide needed to enhance surface-mediated lipofection is less than the amount of peptide needed to enhance lipofection performed by bolus delivery of complexes. In addition to tissue-culture polystyrene, multiple surface chemistries are being investigated for surface-mediated gene delivery of peptide-lipoplexes. These peptide-lipoplexes demonstrate a robust and tunable gene delivery system that can be used to investigate the mechanisms of non-viral gene delivery.