title: Generation of Targeted Adeno-Associated Virus (AAV) Vectors for Human Gene Therapy.
abstract: Adeno-associated virus (AAV) vectors are promising human gene delivery vehicles due to their ability to establish long-term gene expression in a wide variety of target tissues; however, the broad native viral tropism raises concerns over the feasibility and safety of their systemic administration. To overcome this issue, much effort has been made to redirect AAVs toward specific tissues. This review presents several design strategies that have been applied to generate AAVs that target specific tissues and cells while inhibiting the transduction of non-target tissues. Multiple methods of vector capsid engineering have shown promise in vitro, including indirect targeting by adaptor systems and direct targeting by the insertion of antibodies or receptor-specific small peptide motifs. Other strategies, including creating mosaic or chimeric capsids and directed evolution, have also been used to successfully retarget AAV vectors. This research will further expand the clinical applications of AAV vectors by enhancing the control over tissue-specific gene delivery.
authors.affiliation: University of Southern California, Mork Family Department of Chemical Engineering and Materials Science, 3710 McClintock Ave, RTH-509, Los Angeles, California 90089, United States of America. yarongli@usc.edu.
authors.forename: Yarong
authors.initials: Y
authors.lastname: Liu
authors.forename: Natnaree
authors.initials: N
authors.lastname: Siriwon
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Rohrs
authors.forename: Pin
authors.initials: P
authors.lastname: Wang
mesh_terms: D000229:Dependovirus / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans