Adenoviruses are efficient vectors for the in vivo gene delivery in gene therapy. Adenoviruses efficiently infect many cell/tissue types and express therapeutic genes. However, viral infection of healthy tissues can cause toxicity and adverse effects. A therapeutic approach that targets the virus to diseased tissue while preventing infection of surrounding healthy tissue would be optimal. Our proposal attempts to address both of these issues by blocking native adenoviral infection, and specifically redirecting virus to disease tissues using a fusion protein with an antibody Fc binding domain. This protein adaptor has a unique strength: it can be flexibly adapted to target any marker for which there is a specific antibody. Our studies have demonstrated in endothelial culture that adenovirus, fusion protein and antibody complex could target the ICAM-l receptor while blocking native infection pathway. We propose to test our strategy in vivo targeting glioblastoma, a fatal disease for which no effective therapy present. The interleukin-13 receptor was found overexpressed on many glioblastomas and thus can be used as a specific marker for targeting. The goal is to demonstrate the feasibility of our strategy to mediate specific adenoviral infection in a murine xenografted glioblastoma model. This technology may ultimately improve gene therapy.
