Translating Sleeping Beauty transposition into cellular therapies: victories and challenges.
Recent results confirm that long-term expression of therapeutic transgenes can be achieved by using a transposon-based system in primary stem cells and in vivo. Transposable elements are natural DNA transfer vehicles that are capable of efficient genomic insertion. The latest generation, Sleeping Beauty transposon-based hyperactive vector (SB100X), is able to address the basic problem of non-viral approaches - that is, low efficiency of stable gene transfer. The combination of transposon-based non-viral gene transfer with the latest improvements of non-viral delivery techniques could provide a long-term therapeutic effect without compromising biosafety. The new challenges of pre-clinical research will focus on further refinement of the technology in large animal models and improving the safety profile of SB vectors by target-selected transgene integration into genomic "safe harbors." The first clinical application of the SB system will help to validate the safety of this approach.
Izsvák
Zsuzsanna
Z
Max-Delbrück Center for Molecular Medicine (MDC), Berlin, Germany. zizsvak@mdc-berlin.de
Hackett
Perry B
PB
Cooper
Laurence J N
LJ
Ivics
Zoltán
Z
D000818:Animals; D004251:DNA Transposable Elements; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D016254:Mutagenesis, Insertional; D019076:Transgenes; D019895:Transposases / Q000235:genetics*
D004251:DNA Transposable Elements; D019895:Transposases; C494471:sleeping beauty transposase, human