Synthetic Gene Delivery Vehicles

The delivery of intravenous nucleic acid therapies is hampered by the rapid degradation of naked nucleic acids by enzymes found in blood. The use of a delivery vehicle to protect therapeutic nucleic acids greatly improves the nuclease resistance and circulation thus prolonging the therapeutic effect in vivo. In order to overcome the shortcomings (immune response, lack of cell specificity, and high cost of manufacture) of viral vectors, we synthesize block copolymers comprised of a hydrophilic block for steric stabilization and a cationic block capable of complexing negatively-charged nucleic acids. Upon complexation, the block copolymer and nucleic acid compact into nanoparticles called “polyplexes” which protect the nucleic acids from enzymatic degradation and allow transport into cells through endocytotic mechanisms. Our studies focus on the effect the block copolymer properties such as composition, molecular weight, block length, degradability, concentration of cationic charge, and stimuli-responsiveness have on the delivery of nucleic acids in vivo and in vitro.

Representative Publications

  • Hemp, S. T.; Allen, Jr., M. H.; Smith, A. E.; Long, T. E. “Synthesis and Properties of Sulfonium Polyelectrolytes for Biological Applications” ACS Macro Letters (2013), 2(8), 731–735.


  • Hemp, S. T.; Smith, A. E.; Bryson, J. M.; Allen, Jr., M. H.; Long, T. E. “Phosphonium-Containing Diblock Copolymers for Enhanced Colloidal Stability and Efficient Nucleic Acid Delivery” Biomacromolecules (2012), 13(8), 2439–2445.


  • Smith, A. E.; Sizovs, A.; Grandinetti, G.; Xue, L.; Reineke, T. M. “Diblock Glycopolymers Promote Colloidal Stability of Polyplexes and Effective pDNA and siRNA Delivery in Physiological Salt and Serum Conditions” Biomacromolecules (2011), 12(8), 3015-3022.