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Show 63 college of pharmacy Virus-based gene therapy has shown its potential as a form of treatment for cancer. Currently, the forms of delivery for gene therapy treatment are limited by a low ratio of efficacy to toxicity. For ef-fective treatment, viral vectors must reach a majority of tumor cells and not be cleared out by the liver upon injection to the body. A potential delivery system for effective gene therapy treatment is Silk- Elastinlike Protein Polymers (SELPs). SELPs are recombinant polymers that contain silk fibroin and mammalian elastin amino acid repeats that determine the chemical properties of the polymer. Upon injection to the body, SELP copolymers undergo an irreversible sol-to-gel transition forming mechanically robust hydrogels that can deliver plasmid DNA into solid tumors for up to 21 days. Unfortunately, the SELPs that have been tested in vivo do not clear out of the body efficiently after gene delivery, which could cause further complica-tions by the buildup of collagen around the hydrogel. SELP-815K (8 silk fibroin repeats and 15 mammalian elastin repeats with K representing a lysine unit) has been shown to have the highest transfection efficiency out of the SELPs that have been engi-neered. Currently, SELP-815K is being constructed to incorporate a MMP-responsive sequence that is designed to be cleaved by matrix-metalloproteinase (MMP) family enzymes. MMP family enzymes are overexpressed in tumor cells which would allow an increase in the degradation and clearance of the polymer matrix if MMP responsive sites are present. The inserts which encode the MMP responsive sites have been ligated between the mammalian elastin block and the silk fibroin block at either junc-tion in SELP-815K. Due to the fact that the degradation of the hydrogel is hypothesized to increase with an MMP responsive site, inserting an MMP responsive site at both junctions in the vector will al-low the hydrogel to be degraded more efficiently, making the delivery rate of the adenovirus constant. It will also allow the hydrogel to be broken down more efficiently allowing for a faster elimination rate, preventing the buildup of collagen around the hydrogel, and reducing the chances of further medical complications. SILK-ELASTINLIKE PROTEIN POLYMERS WITH MMP-RESPONSIVE SEQUENCES FOR ADENOVIRAL GENE DELIVERY Jeremy Hammer (Hamid Ghandehari) Ghandehari Research Group Department of Pharmaceutical Chemistry University of Utah UNDERGRADUATE RESEARCH ABSTRACTS Jeremy Hammer Hamid Ghandehari |