title: Adeno-associated virus structural biology as a tool in vector development.
abstract: Adeno-associated viruses (AAVs) have become important therapeutic gene delivery vectors in recent years. However, there are challenges, including intractable tissues/cell types and pre-existing immune responses, which need to be overcome for full realization of this system. This review addresses strategies aimed at improving AAV efficacy in the clinic through the creation of hybrid vectors that display altered or more targeted specific tissue tropisms, while also escaping recognition from host-derived neutralizing antibodies. Characterization of these viruses with respect to serotypes contributing to their capsid, using available 3D structures, enables the identification of regions critical for particular tropism and antigenic phenotypes. Structural information also allows for rational design of vectors with specific targeted tropisms for improved therapeutic efficacy.
authors.affiliation: Department of Biochemistry & Molecular Biology, Center for Structural Biology, The McKnight Brain Institute, College of Medicine, 1600 SW Archer Road, PO Box 100245, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Drouin
authors.affiliation: Department of Biochemistry & Molecular Biology, Center for Structural Biology, The McKnight Brain Institute, College of Medicine, 1600 SW Archer Road, PO Box 100245, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Mavis
authors.initials: M
authors.lastname: Agbandje-McKenna
keywords: adeno-associated virus; capsid structure; chimera; directed evolution; gene therapy; rational design; tissue tropism