The Sleeping Beauty (SB) transposon/transposase system has recently been applied in clinical trials to redirect T-cell specificity through the addition of a transgenic cassette that drives expression of a chimeric antigen receptor. This chapter focuses on issues relating to insertional mutagenesis in the context of the plasticity of human genomes; the unexpected variability in human genomes elucidated by recent high-throughput, whole-genome sequencing; and the recently discovered high rates of remobilization of endogenous transposable elements. These findings are discussed in the context of using SB transposons to treat human disease and suggest that integration by SB transposons is not likely to induce adverse events in the clinic.
|Original language||English (US)|
|Title of host publication||Translating Gene Therapy to the Clinic|
|Subtitle of host publication||Techniques and Approaches|
|Number of pages||19|
|State||Published - 2015|
Bibliographical noteFunding Information:
We thank Drs Judy S. Moyes, Harjeet Singh (MD Anderson Cancer Center) and Dr Elena Aronovich (University of Minnesota) for careful reading and editing of the manuscript and our colleagues in the Center for Genome Engineering for many insightful discussions. We acknowledge the financial support of National Institutes of Health grants 1R01DK082516 and P01-HD32652 (PH), CA16672, CA124782, CA120956, CA141303, CA163587, and CA148600 (LJNC), and 5R00CA151672-04 and P30 CA77598 (TKS).
© 2015 Elsevier Inc. All rights reserved..
- AAPC, Artificial antigen-presenting cell
- CAR, Chimeric antigen receptor
- HSC, Hematopoietic stem cell
- ITR, Inverted terminal repeat
- LINE/SINE, Long/short interspersed elements
- SB, Sleeping Beauty