Adeno-associated virus: fit to serve

• Published in: Current opinion in virology Vol. 8; pp. 90 - 97
• Main Authors: Zinn, Eric, Vandenberghe, Luk H
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2014
• Subjects: Adeno-associated virus; Biological Evolution; Dependovirus - genetics; Dependovirus - immunology; Dependovirus - physiology; Directed Molecular Evolution; Genetic Therapy - methods; Genetic Vectors; Humans; Parvovirus; Selection, Genetic; Viral Tropism
• ISSN: 1879-6257; 1879-6265; 1879-6265
• DOI: 10.1016/j.coviro.2014.07.008

•The adeno-associated virus (AAV) is attractive for use as a gene therapy vector.•The parvoviral capsid evolves to modify receptor binding and host immunity.•AAV relies on a helper-virus infection to go through replication.•AAV is under selective pressure to alter receptor binding and evade host immunity.•Laboratory-based directed evolution is guiding gene therapy vector development. 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.