ABSTRACT:
Nucleic acid cargoes offer unmatched diversity in gene regulatory potential and therapeutics, and understanding of nucleic acid functionality continues to expand rapidly and dramatically through seminal discoveries including RNA interference approaches and gene editing technologies. In nature, the basis for gene regulation is ultimately encoded by the exquisite specificity with which cells are able to control both the location and accessibility of nucleic acid constructs to govern their activation states. My research program seeks to understand and control gene activation using synthetic constructs through nature-inspired approaches to control and quantify cell binding interactions and stability in polymer and peptide nanocarriers. The basis of our approaches is the design of stimuli-responsive polymers and peptides whose interactions with nucleic acids and cells can be controlled dynamically by specific intracellular or external triggers. We exploit our ability to control nucleic acid binding/release and cellular processing to gain new mechanistic insights over nucleic acid delivery, leading to design advances including histone-inspired DNA targeting, light-responsive gene silencing, and collagen turnover-stimulated gene expression. This talk will highlight ways we have used nature-inspired peptides and responsive polymers to control gene transfer in regenerative medicine.