title: Enhancing gene delivery of adeno-associated viruses by cell-permeable peptides.
abstract: Adeno-associated 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 as a result of impaired intracellular viral processing. We also demonstrated that this approach could be applicable to other AAV serotypes. Thus, the membrane-penetrating ability of CPPs enables us to generate an efficient method for enhanced gene delivery of AAV vectors, potentially facilitating its applicability to human gene therapy.
authors.affiliation: Mork Family Department of Chemical Engineering and Materials Science, University of Southern California , Los Angeles, California, USA.
authors.forename: Yarong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Physiology and Biophysics, University of Southern California , Los Angeles, California, USA.
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern California , Los Angeles, California, USA.
authors.forename: Man
authors.initials: M
authors.lastname: Ji
authors.affiliation: Mork Family Department of Chemical Engineering and Materials Science, University of Southern California , Los Angeles, California, USA.
authors.forename: Jinxu
authors.initials: J
authors.lastname: Fang
authors.affiliation: Mork Family Department of Chemical Engineering and Materials Science, University of Southern California , Los Angeles, California, USA.
authors.forename: Natnaree
authors.initials: N
authors.lastname: Siriwon
authors.affiliation: Department of Physiology and Biophysics, University of Southern California , Los Angeles, California, USA.
authors.forename: Li I
authors.initials: LI
authors.lastname: Zhang
authors.affiliation: Mork Family Department of Chemical Engineering and Materials Science, University of Southern California , Los Angeles, California, USA ; Department of Biomedical Engineering, University of Southern California , Los Angeles, California, USA ; Department of Pharmacology and Pharmaceutical Sciences, University of Southern California , Los Angeles, California, USA.
authors.forename: Pin
authors.initials: P
authors.lastname: Wang