Silk-Elastinlike Protein Polymer Hydrogels for Localized Adenoviral Gene Therapy of Head and Neck Tumors

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Abstract
Vector dissemination, transient gene expression, and rapid clearance are major obstacles to successful human gene therapy. In this study, we investigated the effect of silk-elastinlike protein polymer (SELP) hydrogels on biodistribution and anticancer efficacy of adenoviral gene therapy in a head and neck cancer model. Transcriptional activities of adenovirus carrying β-galactosidase (Ad-LacZ) and luciferase (Ad-Luc) reporter genes were evaluated in (nu/nu) mice with head and neck cancer as a function of polymer concentration. Antitumor efficacy of thymidine kinase encoding adenovirus (Ad-Tk) and ganciclovir (GSV) combination was also evaluated. SELP (4 wt %) matrices localized viral release, minimized dissemination to liver, and enhanced reporter gene expression levels by 4−8-fold compared to virus alone. SELP- Ad-Tk with GSV reduced tumor volume significantly compared to the virus alone. SELPs provide a means for temporal and spatial control of viral gene delivery to head and neck tumors.