INTRODUCTION: Recombinant protein polymers are a new and emerging class of materials which combine the versatility, control over structure, and reproducibility of proteins with the speed of production of traditional synthetic polymers. Silk-ElastinLike Protein polymers (SELPs) are one class ofrecombinant polymers which has been considered as an injectable delivery depot for anticancer gene therapy. The purpose of this study is to assess the ability of SELP hydrogels to control the biodistribution of co-injected viruses carrying reporter genes, and to assess the biodegradation of SELP hydrogels in the presence of elastase. METHODS: Two subcutaneous flank tumors were grown using Head and Neck Squamous Cell Carcinoma cells (JHU-022) and then injected with SELP polymer with and without adenovirus carrying a gene encoding for β-galactosidase. At select time points, mice were sacrificed and organ lysates were assayed for β-gal expression using an enzyme activity assay. For the assessment of biodegradation, SELP hydrogels were exposed to varying concentrations of elastase in a saline release medium, and the amount of soluble protein released from the hydrogels was measured over time. RESULTS: The results of this study show that the biodistribution of virus co-injected with SELP is more controlled than the distribution of an injection of virus alone. Additionally, these studies show structure-dependent differences in the extent of control over biodistribution in vivo. Preliminary results show that elastase causes a significant increase in the amount of soluble protein over time compared to an elastase-free control. Work is ongoing to investigate the dose-response relationship and biochemical nature of this degradation. CONCLUSIONS: The results of these studies encourage further investigation into the utility of SELP polymer hydrogels as controlled release depot material for the delivery of virus-mediated anticancer gene therapy.

Acknowledgement: Funding for this study was provided under NIH R01 CA107621.