CAR- or αv integrin-binding ablated adenovirus vectors, but not fiber-modified vectors containing RGD peptide, do not change the systemic gene transfer properties in mice

摘要: Targeted gene delivery to the tissue of interest by recombinant adenovirus (Ad) vectors is limited relatively broad expression primary receptor, coxsackievirus and receptor (CAR), secondary αv integrin. This problem could be overcome mutating fiber penton base, which bind with CAR integrin, respectively. In this study, we constructed CAR-binding ablated Ad integrin-binding mutation in FG loop knob RGD motif respectively, compared transfer properties their into various types cultured cells mice conventional vectors. We also generated containing peptide HI knob. mediated about 1% activity CAR-positive cells, vectors, while maintained at least 76% cells. Inclusion restored vitro. On other hand, systemically administered as well similar levels mouse liver These results suggest that continued interaction either or base integrin offers an effective route virus entry vivo. Inhibition both likely crucial development targeted