Directed evolution of adeno-associated virus yields enhanced gene delivery vectors
- PMID: 16429148
- DOI: 10.1038/nbt1182
Directed evolution of adeno-associated virus yields enhanced gene delivery vectors
Abstract
Adeno-associated viral vectors are highly safe and efficient gene delivery vehicles. However, numerous challenges in vector design remain, including neutralizing antibody responses, tissue transport and infection of resistant cell types. Changes must be made to the viral capsid to overcome these problems; however, very often insufficient information is available for rational design of improvements. We therefore applied a directed evolution approach involving the generation of large mutant capsid libraries and selection of adeno-associated virus (AAV) 2 variants with enhanced properties. High-throughput selection processes were designed to isolate mutants within the library with altered affinities for heparin or the ability to evade antibody neutralization and deliver genes more efficiently than wild-type capsid in the presence of anti-AAV serum. This approach, which can be extended to additional gene delivery challenges and serotypes, directs viral evolution to generate 'designer' gene delivery vectors with specified, enhanced properties.
Comment in
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AAV does the shuffle.Nat Biotechnol. 2006 Feb;24(2):158-60. doi: 10.1038/nbt0206-158. Nat Biotechnol. 2006. PMID: 16465157 No abstract available.
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