Building better gene vectors

Gene therapy requires highly efficient recombinant adenoviral vectors that can induce lifelong therapeutic gene expression, but it has been unclear how such a vector can best be engineered. In September 16 Nature Biotechnology, Stephen Yant and colleagues at Stanford University School of Medicine, show that a gene-deleted adenovirus–transposon vector can stabilize transgene expression in vivo (Nature Biotechnology, DOI:10.1038/nbt738, September 16, 2002).

Yant et al. incorporated the Sleeping Beauty integration machinery into an adenoviral vector and also created a donor transposon vector that undergoes Flp-mediated recombination and excision of its therapeutic payload in the presence of Flp and SB recombinases. These vectors achieved efficient generation of transposon circles and stable transposase-mediated integration into mouse liver. In addition, they showed that somatic integration using this delivery system was sufficient to maintain therapeutic levels of human coagulation Factor IX for more than six months in mice undergoing extensive liver...