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Open Access Highly Accessed Review

Creation of a cardiotropic adeno-associated virus: the story of viral directed evolution

Lin Yang1 and Xiao Xiao2

Author Affiliations

1 Wuhan Institute of Virology, Chinese Academy of Sciences, 44 Xiaohongshan, Wuhan, 430071, Hubei, China

2 Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, 2070 Genetic Medicine Building CB#7362, Chapel Hill, NC, 27599, USA

Virology Journal 2013, 10:50  doi:10.1186/1743-422X-10-50

Published: 11 February 2013

Abstract

Adeno-associated virus (AAV) is an important vector system for human gene therapy. Although use of AAV serotypes can result in efficient myocardial gene transfer, improvements in the transduction efficiency and specificity are still required. As a method for artificial modification and selection of gene function, directed evolution has been used for diverse applications in genetic engineering of enzymes and proteins. Since 2000, pioneering work has been performed on directed evolution of viral vectors. We further attempted to evolve the AAV using DNA shuffling and in vivo biopanning in a mouse model. An AAVM41 mutant was characterized, which was found to have improved transduction efficiency and specificity in myocardium, an attribute unknown for any natural AAV serotypes. This review focuses on the development of AAV vector for cardiac gene transfer, the history of directed evolution of viral vectors, and our creation of a cardiotropic AAV, which might have implications for the future design and application of viral vectors.

Keywords:
Adeno-associated virus; Cardiac gene transfer; Directed evolution; Transduction