The use of synthetic polymers for the delivery of nucleic acids holds considerable promise for understanding and treating disease at the molecular level. A major effort in our lab aims to develop novel synthetic glycopolymer nucleic acid delivery vehicles we have termed poly(glycoamidoamine)s (PGAAs). These materials have revealed excellent plasmid DNA delivery profiles, in particular, with primary cell types. Here in, we present an alternative method to synthesize analogous systems via reversible addition-fragmentation chain transfer polymerization (RAFT) polymerization. RAFT has quickly emerged as a facile technique to create highly controlled macromolecules from monomers containing functional groups that would normally not be tolerated with conventional polymerization techniques. Herein, we report the RAFT synthesis of diblock glycopolymers comprised of 2-deoxy-2-methacrylamido glucopyranose (MAG) to promote colloidal stability in salt and serum conditions and N-(2-aminoethyl)methacrylamide (AEMA) for nucleic acid complexation and compaction into polyplexes. We utilize dynamic light scattering (DLS) to assess the salt and serum stability of the polyplexes formed between the novel glyocpolymers and various nucleic acid types. Cell culture experiments demonstrate high cellular uptake and low cytotoxicity of the polyplexes and preliminary studies show they are excellent pDNA and siRNA delivery vehicles.

Glycopolycations created via RAFT polymerization are serum stable and effective siRNA delivery vehicles

241st National Meeting (2011)

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