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.
|Title of host publication
|Translating Gene Therapy to the Clinic
|Subtitle of host publication
|Techniques and Approaches
|Number of pages
|Published - 2015
Bibliographical notePublisher Copyright:
© 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