Development of peptide-based polymers for gene transfer to the CNS

S.H. Pun
University of Washington, US

Keywords: polymer, drug delivery, gene transfer, central nervous system

Summary:

Living polymerization is a versatile method for synthesizing polymeric materials with well-defined characteristics. We have recently demonstrated the living polymerization can be used to generate peptide-based polymers with controlled molecular weights and peptide composition. In this talk, I will describe the application of these polymers for nucleic acid delivery. Peptide-based polymers were designed to include components to bind and condense DNA, mediate preferential interaction with neuronal cells, and facilitate release from endosomes after cell uptake. In addition, two types of degradable peptide-copolymers were synthesized. Reducible polymers were synthesized using peptide monomers containing internal disulfide bonds. Enzymatically-cleavable polymers were synthesized using peptide monomers containing cathepsin B-cleavable sequences. The biological applications of these materials and gene transfer agents were assessed both in cultured cells and mice models. We demonstrate that peptide-HPMA copolymers are a flexible platform for designing multifunctional materials.