Mobilization of DNA transposable elements from lentiviral vectors.

With the Sleeping Beauty (SB) DNA transposon, a reconstructed Tc1/mariner element, as the driving force, DNA transposable elements have emerged as new gene delivery vectors with therapeutic potential. The bipartite transposon vector system consists of a transposon vector carrying the transgene and a source of the transposase that catalyzes transposon mobilization. The components of the system are typically residing on separate plasmids that are transfected into cells or tissues of interest. We have recently shown that SB vector technology can be successfully combined with lentiviral delivery. Hence, SB transposons are efficiently mobilized from HIV-based integrase-defective lentiviral vectors by the hyperactive SB100X transposase, leading to the genomic insertion of lentivirally delivered DNA in a reaction controlled by a nonviral integration machinery. This new technology combines the better of two vector worlds and leads to integration profiles that are significantly altered and potentially safer relative to conventional lentiviral vectors. In this short commentary, we discuss our recent findings and the road ahead for hybrid lentivirus-transposon vectors.