Browsing by Subject "DNA vaccine"
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Item Improving polymer-mediated DNA vaccine delivery.(2011-06) Palumbo, Rebecca NoelleVaccination using antigen-encoding plasmid DNA has great potential to generate strong immune response against delivered antigen. In order to effectively generate immune response, antigen must be delivered to antigen presenting cells, primarily dendritic cells (DCs). Using cationic polymers as a delivery vehicle can provide many advantages, including protection of DNA from degradation, ability to add targeting moieties, and easy modification of structure to optimize various properties. We have investigated the use of polyplexes as a DNA delivery vehicle in a variety of settings. We demonstrated the feasibility of using the CD40L as a DC targeting moiety, a protein capable of both binding and stimulating DC maturation, using coated nanoparticles. We have also studied the possibility of delivering antigen through transfection of bystander cells rather than direct expression by DCs using an in vitro model. We confirmed the ability of these DCs to present antigen, become mature, and stimulate T cells. Finally, we studied the interaction of cationic polymer complexes in vivo, both in respect to local tissue dispersion and interaction with specific cell types, using fluorescently labeled DNA. Through these experiments we have illuminated potential pathways for optimizing DNA vaccine efficiency using polymer complexes with slightly different structures.Item Trafficking and efficacy of cationic polymers as DNA vaccine carriers and anti-cancer agents(2013-06) Panus, DavidThe potential of DNA vaccines for treatment of diseases such as HIV and cancer are overwhelming, due to the fact that DNA vaccines can activate both a cell-mediated (T-cell) and humoral (antibody) immune response. However, the most commonly occurring problem of DNA vaccines is limited transgene delivery and expression. Currently, much effort has focused on designing an optimal polymer system that is stable, can protect and deliver DNA, as well as offer high transgene expression. Unfortunately, the ability of polymer based systems to produce robust gene expression, have yet to show substantial improvement. The major obstacle hindering successful transgene expression can be attributed to the interactions of the polymer-DNA complex with the subcellular environment. Therefore, we focused on understanding the structure-functional relationship of a well-defined simple polymer based system and how they might lead to improved transgene expression. First, we investigated the effect of polymer molecular weight and backbone structure on transgene expression as it pertains to subcellular trafficking. Second, we focused on the relationship between polymer-DNA complexes and different dendritic cell-types as a function of maturation state. Lastly, we looked into how further modification of a cationic polymer can lead to elevated cytotoxicity and use as an anti-cancer agent. The results from this work can be used as a design template to improve the overall subcellular trafficking and efficacy of cationic polymer based DNA vaccines or anti-cancer agents.