Enhancing in Vitro and in Vivo Gene Delivery of Adeno-Associated Viruses Type 2 By Cell-Permeable Peptides

Adeno-assocated virus type 2 (AAV2) is considered a promising gene delivery vector and has been extensively applied in several disease models; however, inefficient transduction in various cells and tissues has limited its widespread application in many areas of gene therapy. In this study, we have developed a general but efficient strategy to enhance viral transduction both in vitro and in vivo, by incubating viral particles with cell-permeable peptides (CPPs).  We show that CPPs increase internalization of viral particles into cells by facilitating both energy-independent and energy-dependent endocytosis. Moreover, CPPs can significantly enhance the endosomal escape process of viral particles, thus enhancing viral transduction to those cells that have exhibited very low permissiveness to AAV2 infection due to impaired intracellular processing of virus. Thus, the membrane-penetrating ability of CPPs enables us to generate an efficient method for enhanced gene delivery of AAV2 vectors, potentially facilitating its applicability to human gene therapy.