Research Project Title:
Efficient Cellular Delivery of DNA Nanoparticles
abstract:Cell-penetrating peptides (CPPs) have recently emerged as one of the most effective tools for drug delivery in various cell types, in particular in tissue compartments that are difficult to access. CPPs can facilitate both cell entry and escape from intracellular degradation. However, the mechanisms by which CPPs enter cells and escape degradation are not fully understood, largely due to the differing physicochemical properties, size, and concentration of CPPs or CPP-cargo conjugates. Nonetheless, these factors can play a significant role in efficiency of cell entry and escape of degradation. DNA origami nanoparticles can address these challenges by serving as a bioorthogonal vehicle with easily tunable stoichiometric attachment of CPPs. Moreover, cell-targeting ligands can be simultaneously conjugated to the nanoparticle to allow for cell type-specific delivery while reducing intracellular degradation. This project will investigate how tuning CPP number and spacing can limit particle degradation. Using CPPs conjugated to tetrahedral DNA nanoparticles in conjunction with cell-targeting ligands, we will identify optimal parameters to enhance the efficacy of therapeutics.
"I am eager to take advantage of the SuperUROP opportunity to continue my current bioengineering UROP project. I look forward to growing as a presenter, thinker, and researcher through the program and hope to work towards a publication from my SuperUROP work. I'm most excited about the project because enhanced targeted cellular delivery would be an impactful advance for DNA nanotechnology-based therapeutics."