Investigational therapy can be successfully undertaken using viral- and nonviral-mediated ex vivo gene transfer. Indeed, recent clinical trials have established the potential for genetically modified T cells to improve and restore health. Recently, the Sleeping Beauty (SB) transposon/transposase system has been applied in clinical trials to stably insert a chimeric antigen receptor (CAR) to redirect T-cell specificity. We discuss the context in which the SB system can be harnessed for gene therapy and describe the human application of SB-modified CAR+ T cells. We have focused on theoretical issues relating to insertional mutagenesis in the context of human genomes that are naturally subjected to remobilization of transposons and the experimental evidence over the last decade of employing SB transposons for defining genes that induce cancer. These findings are put into the context of the use of SB transposons in the treatment of human disease.
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Conflict of interests: All authors have read the journal’s policy on conflicts of interest. PBH and DAL have equity in Discovery Genomics, Inc., a small biotech company that receives funding from the NIH to explore the use of transposons for gene therapy.
Supported by National Institutes of Health grants 1R01DK082516 and P01-HD32652 (P.H.), CA16672 , CA124782 , CA120956 , CA141303 , CA163587 , and CA148600 (L.J.N.C.), and R01CA113636 , R01CA134759 (D.A.L.).
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