Transposon-based Vector Systems for Gene Therapy Clinical Trials: Challenges and Considerations

Much progress has been made in gene therapy, but significant challenges remain. One is development of a range of different tools that can be used for different therapeutic purposes.Another is site-specific gene targeting for safe and faithfultherapeutic gene expression. Viruses have long been conside r e d t h e mo s t p r omi s i n g t o o l s f o r h uma n g e n e t h e r a p y.However, fatal side effects associated with viral vectors havehampered their clinical application. DNA transposons, widelyutilized for decades as genetic tools in plants and insects, arenow emerging as viable vectors for gene therapy. In this article, we will give a brief review of the adverse effects associated with virus-based gene therapy followed by a glimpse of theadeno-associated virus vector system, which is currently themost promising viral vector for gene therapy. The developmentof DNA transposon-based gene delivery systems and theadvantages and limits of the most commonly used DNA transposon systems, SleepingBeauty, Tol2, and piggyBac, will be extensively discussed Finally, we will focus on the mostpromising transposon system for gene therapy, piggyBac. Challenges and considerations foradvancing piggyBac for therapeutic application will be critically addressed.