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Mentor: Kevin G. Rice, PhD
Year Entered Into Program: 2004-2009
PhD Institution: University of Iowa, 2009
Gene therapy has not reached its full potential in the
prevention and treatment of disease. Non-viral vectors are gaining wide
utility as a means of gene delivery due to the control one has when
synthesizing a carrier, which can lead to increases in efficacy and safety.
Non-viral vectors can be constructed efficiently and with high
reproducibility. In addition, non-viral DNA condensates can be dosed
repeatedly with little or no immune response or cytotoxicity. Two important
elements in designing a non-viral vector are to design a compound which
targets a specific receptor or cell type, and to devise a means of protecting
therapeutic DNA from intracellular degradation and DNAses. The focus of my
research in the Rice lab is to synthesize DNA carrier molecules with a ligand
specific to the mannose receptor, and with properties which render it
resistant to intracellular degradation. Because our DNA condensates are
mannoseylated, we have been able to target Kupffer cells in-vivo with high
specificity. In our future work we will be targeting Dendritic cells bearing
the SIGN receptor, a related C-type lectin which binds mannose. DC-SIGN
mediates transient adhesion with T-cells, and this contact is essential in
initiating a primary immune response.
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