title: Adeno-associated virus: fit to serve.
abstract: Adeno-associated virus (AAV) is a helper-dependent parvovirus which has not been linked with human disease. This aspect, in combination with its broad cell and tissue tropism, and limited viral host response has made it an attractive vector system for gene therapy. The viral protein capsid, the primary interface with the host, is the main determinant for these phenotypes, is highly variable, and is most subject to pressures during replication. Here, we explore the evolutionary path of AAV and other parvoviruses in respect to these phenotypes, as well as directed evolution and engineering strategies that have exploited the lessons learned from natural selection in order to address remaining limitations of AAV as a therapeutic gene transfer platform.
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, United States.
authors.forename: Eric
authors.initials: E
authors.lastname: Zinn
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, United States. Electronic address: luk_vandenberghe@meei.harvard.edu.
authors.forename: Luk H
authors.initials: LH
authors.lastname: Vandenberghe
mesh_terms: D005075:Biological Evolution; D000229:Dependovirus / Q000235:genetics / Q000276:immunology* / Q000502:physiology*; D019020:Directed Molecular Evolution; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D012641:Selection, Genetic; D056189:Viral Tropism