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Transl Res. 2013 Apr;161(4):265-83. doi: 10.1016/j.trsl.2012.12.005. Epub 2013 Jan 10.

Evaluating risks of insertional mutagenesis by DNA transposons in gene therapy.

Author information

1
Department of Genetics Cell Biology and Development, Center for Genome Engineering and Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA. perryh@umn.edu

Abstract

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.

PMID:
23313630
PMCID:
PMC3602164
DOI:
10.1016/j.trsl.2012.12.005
[Indexed for MEDLINE]
Free PMC Article
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