1095. Silica Gel in Targeted and Controlled Viral Gene Therapy

Silica gel is a solid, non-toxic 100 % biodegradable matrix suitable for delivery of small molecules and proteins as implant material in vivo. Here, silica gel was investigated as carrier of adenoviral vectors in controlled and localized gene delivery. Recombinant adenoviruses coding for beta-galactosidase (lacZ) were encapsulated in silica gel prepared from water and tetraethoxysilane by sol-gel method in molar ratio of 52.5:1. The sol-gel process was modified so that addition of adenoviruses was possible into the liquid sol. After the gel formation the adenoviruses became encapsulated inside solid gel structure. Monolithic buttons of adenovirus-loaded silica gels for in vitro tests were soaked in PBS, and incubated at +37 °C, 5 % CO2 or in RT, and cultured with human skin fibroblasts for different periods of time up to 32 days. Transduction of fibroblasts by adenoviruses released from silica gel was determined by X-gal staining. In parallel, adenoviruses were incubated in solution at +37 °C, and the virus titres in conditioned media were determined daily. In vivo experiments were carried out by implanting the adenovirus-loaded silica gel s.c. into the neck of mice. At time points of 3, 7, 14 and 21 days animals were sacrificed, tissue samples were collected and stainedby X-gal. At the same time points, blood samples were obtained and antibodies against adenovirus serotype 5 were determined.