The Sleeping Beauty transposon system for clinical applications

Extensive efforts have been made to establish efficient and safe gene delivery protocols that could meet demanding expectations of a successful gene therapy. The Sleeping Beauty (SB) transposon system combines simplicity and inexpensive manufacture offered by plasmid-based vector formulation with integrative features exhibited by some viral vectors. Activated after over ten million years of silent genomic existence, the SB transposable element entered the 21st century as a potent technology for a broad range of applications in genome engineering, including gene therapy. Beneficially for gene therapy purposes, the SB system has been demonstrated to enable persistent expression of therapeutic genes followed by restoration of homeostasis in a variety of disease models. Importantly, this non-viral gene delivery vehicle is postulated to constitute a relatively safe vector system, because it lacks a preference for inserting into transcription units and their upstream regulatory regions, thereby minimizing genotoxic risks that might be associated with vector integration. Further evolution and wide, comprehensive preclinical testing of the SB transposon system in the context of several disease models is expected to further refine this valuable technology matched by enhanced biosafety towards disease treatment.