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Biotech / Medical : Gene therapy

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To: Mike McFarland who started this subject7/13/2002 8:14:04 PM
From: scaram(o)uche  Read Replies (2) of 319
 
I don't follow this stuff, but I ran across it. SnowShredder, probably MauiMan in the summer, should be recruited for comment........

Nature Biotechnology
July 2002 Volume 20 Number 7 pp 697 - 701

Efficient mouse airway transduction following recombination between AAV vectors carrying parts of a larger gene

Christine L. Halbert, James M. Allen & A. Dusty Miller

Fred Hutchinson Cancer Research Center, Seattle, WA 98109.
Correspondence should be addressed to A D Miller. e-mail: dmiller@fhcrc.org

The small packaging capacity of adeno-associated virus (AAV) vectors limits the utility of this promising vector system for transfer of large genes. We explored the possibility that larger genes could be reconstituted following homologous recombination between AAV vectors carrying overlapping gene fragments. An alkaline phosphatase (AP) gene was split between two such AAV vectors (rec vectors) and packaged using AAV2 or AAV6 capsid proteins. Rec vectors having either capsid protein recombined to express AP in cultured cells at about 1–2% of the rate observed for an intact vector. Surprisingly, the AAV6 rec vectors transduced lung cells in mice almost as efficiently as did an intact vector, with 10% of airway epithelial cells, the target for treatment of cystic fibrosis (CF), being positive. Thus AAV rec vectors may be useful for diseases such as CF that require transfer of large genes.
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