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Mentor: Kevin G. Rice, PhD
Year Entered Into Program: 2004-2009
PhD Institution: University of Iowa, 2009
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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