The development of non-viral gene-transfer technologies that can support
stable chromosomal integration and persistent gene expression in vivo
is desirable. Here we describe the successful use of transposon technology
for the nonhomologous insertion of foreign genes into the genomes of adult
mammals using naked DNA. We show that the Sleeping Beauty transposase
can efficiently insert transposon DNA into the mouse genome in approximately
5−6% of transfected mouse liver cells. Chromosomal transposition resulted
in long-term expression (>5 months) of human blood coagulation factor IX at
levels that were therapeutic in a mouse model of haemophilia B. Our results
establish DNA-mediated transposition as a new genetic tool for mammals, and
provide new strategies to improve existing non-viral and viral vectors for
human gene therapy applications.
