Directed Evolution of Adeno - Associated Virus Yields Enhanced Gene Delivery Vectors  

Oleh:

Maheshri, Narrendra ; Koerber, James T. ; Kaspar, Brian K. ; Schaffer, David V.

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Nature Biotechnology: The Science and Business of Biotechnology vol. 24 no. 2 (Feb. 2006), page 198-204.
Topik: gene; AAV; gene

Ketersediaan

Perpustakaan Pusat (Semanggi) Nomor Panggil: NN9.4 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

Adeno associated viral vectors are heighly 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 availavle 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.

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