CAREER: Real-Time Transport Phenomena of Non-Viral DNA Nanocarriers in Live Cells: A Research and Education Program

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Justin S. HanesBES-0346716This proposed research seeks to quantify the rates and efficiencies of particle transport through potential intracellular rate-limiting barriers by using a imaging technique and particle tracking software. The specific aims are: (1) to investigate the effects of gene carrier physicochemical properties on the spatially- and temporally-dependent intracellular transport and accumulation of a variety of important non-viral gene carriers in human primary muscle and endothelial cells, (2) to determine the biological and/or biophysical mechanisms responsible for the intracellular gene carrier transport phenomena, and (3) to identify the effects of attaching combinations of important bioactive ligands to the gene carrier surface on the intracellular transport of the carriers, and correlate this with gene expression. The potential scientific insights to be gained from the proposed research may provide a rational basis for the improved design of new gene carriers capable of more efficient delivery to the cell nucleus. The ability to determine the transport behavior of a heterogeneous population of carriers on an individual carrier basis is critical since only a minute fraction of gene carriers applied to a cell ultimately reaches the nucleus. In addition, two innovative educational initiatives designed to recruit and retain young people, especially underprivileged and underrepresented students, into engineering careers are proposed. The first is a combined coursework and research program for undergraduates with an emphasis on technical communication skills and independent research. The second is a high school outreach research program targeted toward students that come from underprivileged families, or that are part of underrepresented groups in science and engineering.