Journal
GENE THERAPY
Volume 18, Issue 9, Pages 849-856Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/gt.2011.40
Keywords
chimeric antigen receptor; T cells; Sleeping Beauty; SB11; SB100X; CD19
Categories
Funding
- Cancer Prevention Research Institute of Texas, Department of Defense [PO1 (CA100265), CCSG (CA16672), RO1s (CA124782), RO1s (CA120956), R33 (CA116127)]
- Alex's Lemonade Stand Foundation
- Alliance for Cancer Gene Therapy
- Burroughs Wellcome Fund
- Gillson Longenbaugh Foundation
- Harry T Mangurian, Jr, Foundation
- Institute of Personalized Cancer Therapy
- Leukemia and Lymphoma Society
- Lymphoma Research Foundation
- Miller Foundation
- National Foundation for Cancer Research
- Pediatric Cancer Research Foundation
- National Marrow Donor Program
- William Lawrence and Blanche Hughes Foundation
Ask authors/readers for more resources
Sleeping Beauty (SB3) transposon and transposase constitute a DNA plasmid system used for therapeutic human cell genetic engineering. Here we report a comparison of SB100X, a newly developed hyperactive SB transposase, to a previous generation SB11 transposase to achieve stable expression of a CD19-specific chimeric antigen receptor (CAR(3)) in primary human T cells. The electro-transfer of SB100X expressed from a DNA plasmid or as an introduced mRNA species had superior transposase activity in T cells based on the measurement of excision circles released after transposition and emergence of CAR expression on T cells selectively propagated upon CD19(+) artificial antigen-presenting cells. Given that T cells modified with SB100X and SB11 integrate on average one copy of the CAR transposon in each T-cell genome, the improved transposition mediated by SB100X apparently leads to an augmented founder effect of electroporated T cells with durable integration of CAR. In aggregate, SB100X improves SB transposition in primary human T cells and can be titrated with an SB transposon plasmid to improve the generation of CD19-specific CAR(+) T cells. Gene Therapy (2011) 18, 849-856; doi:10.1038/gt.2011.40; published online 31 March 2011
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available