Mentor: Kevin G. Rice, PhD

Year Entered Into Program: 2008

PhD Institution: University of Iowa, 2013

Affiliations

• Medicinal and Natural Products Chemistry

Research Description

Cysteine-flanked, acridinylated peptides are currently being synthesized for prospective use in non-viral gene delivery. Acridine is installed on the side chain of lysine residues to promote intercalation between DNA base pairs, and cysteine-flanking provides a polymerization feature to the peptide via disulfide bonding, which should increase the affinity of the overall polymer for DNA. The disulfide bonds also provide a reversible means of attachment. Once inside the cell, the reductive environment should reduce the disulfide bonding and, in turn, decrease the affinity of the polymer for DNA. If polymerization is successful for these attachment peptides, one can envision the use of cysteine-flanked components of a complete delivery vector being reversibly polymerized and attached to DNA. While polydispersity may prove to be an issue in this process, further studies will be conducted to sequentially attach fragments via deprotection of cysteine with thiol-specific functional groups and subsequent disulfide linkage. This will most likely be accomplished in solid-phase beginning with one terminal peptide of the prospective polymer covalently attached to resin.

Awards

• NIH T32 Pharmacological Sciences Training Grant, University of Iowa, 2009-2011
• MNPC Graduate Student Travel Award, 2012
• ASGCT 15th Annual Meeting Travel Award, 2012

Publications

1. Fernandez, C.A., Baumhover, N.J., Duskey, J.T., Khargharia, S., Kizzire, K., Ericson, M.D., Rice, K.G.:Metabolically stabilized long-circulating PEGylated polyacridine peptide polyplexes mediate hydrodynamically stimulated gene expression in liver. Gene Therapy 18:23-37, 2011.PMCID: PMC2990782
2. Kizzire, K., Khargharia, S., Rice, K.G.:High-Affinity PEGylated Polyacridine Polyplexes Mediate Potent In Vivo Gene Expression. Gene Therapy. 20(4):407-416, 2013. PMCID: PMC3665005