An improved helper-dependent adenoviral vector allows persistent gene expression after intramuscular delivery and overcomes preexisting immunity to adenovirus

摘要: Helper-dependent adenoviral vectors deleted of all viral coding sequences have shown an excellent gene expression profile in a variety animal models, as well reduced toxicity after systemic delivery. What is still unclear whether long-term and therapeutic dosages these can be obtained also the presence preexisting immunity to adenovirus, condition found high proportion adult human population. In this study we performed intramuscular delivery helper-dependent carrying mouse erythropoietin marker transgene. We that low doses direct long-lasting muscles fully immunocompetent mice. The best performance-i.e., 100% treated animals showing sustained 4 months-was achieved with latest generation backbones, which replicate package at efficiency during vector propagation. Moreover, efficient prolonged transgene injection was observed limited load previously immunized against same adenovirus serotype. These data suggest therapy by feasible.