期刊
JOURNAL OF GENE MEDICINE
卷 8, 期 2, 页码 155-162出版社
JOHN WILEY & SONS LTD
DOI: 10.1002/jgm.849
关键词
AAV vectors; directed evolution; combinatorial library; pre-existing immunity; human gene therapy; capsid modification
Background Viruses are being exploited as vectors to deliver therapeutic genetic information into target cells. The success of this approach will depend on the ability to overcome current limitations, especially in terms of safety and efficiency, through molecular engineering of the viral particles. Methods Here we show that in vitro directed evolution can be successfully performed to randomize the viral capsid by error prone PCR and to obtain mutants with improved phenotype. Conclusions Our results demonstrate that combinatorial engineering overcomes the limitations of rational design approaches posed by incomplete understanding of the infectious process and at the same time offers a powerful tool to dissect basic viral biology by reverse genetics. Copyright (c) 2005 John Wiley & Sons, Ltd.
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