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. Dusty Miller 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.
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated
