(251c) Design, Synthesis and Evaluation of Poly (amino ethers) for Efficient Transgene Delivery

Thrimoorthy Potta, Lucas Vu, Kaushal Rege

Chemical Engineering

Arizona State University

Tempe, AZ 85287-6106

A combinatorial library of novel branched cationic poly(aminoethers) was synthesized based on the ring opening polymerization between diglycidyl ethers and poly(amines) with an eye towards rapidly identifying candidates for transgene delivery. Parallel screening of the resulting polymers led to identification of several leads that demonstrated higher transgene expression efficacies and lower cytotoxicities compared to branched pEI (25 kDa) in different cancer cell lines. Polymers were characterized using ¹H NMR, FTIR and GPC analyses. The role of polymer and polyplex physicochemical properties, including pH-buffering capability, DNA binding efficacy, polyplex size and zeta potential, on transgene expression efficacies was investigated. Lead polymers were interfaced with chemotherapeutic drugs (e.g. histone deacetylases inhibitors) in order to further enhance their transgene expression efficacies. Furthermore, polyaminoethers were also employed to enhance virus-mediated transgene expression in several cancer cell lines. These studies indicate that branched cationic poly(aminoethers) are promising candidates for transgene expression using by themselves as non-viral vectors and as polymer-virus hybrids.