| The hyperactive Sleeping Beauty transposase SB100X improves the genetic modification of T cells to express a chimeric antigen receptor. | |
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MedLine Citation:
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PMID: 21451576 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 (CAR3) 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. |
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Authors:
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Z Jin; S Maiti; H Huls; H Singh; S Olivares; L Mátés; Z Izsvák; Z Ivics; D A Lee; R E Champlin; L J N Cooper |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2011-03-31 |
Journal Detail:
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Title: Gene therapy Volume: 18 ISSN: 1476-5462 ISO Abbreviation: Gene Ther. Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-09-08 Completed Date: 2012-01-09 Revised Date: 2013-04-15 |
Medline Journal Info:
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Nlm Unique ID: 9421525 Medline TA: Gene Ther Country: England |
Other Details:
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Languages: eng Pagination: 849-56 Citation Subset: IM |
Affiliation:
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Division of Pediatrics, Children's Cancer Hospital, The University of Texas Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antigens, CD19
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metabolism* Cell Line, Tumor Cytotoxicity, Immunologic Electroporation Gene Transfer Techniques* Humans Neoplasms / immunology RNA, Messenger Receptors, Antigen / genetics, metabolism* T-Lymphocytes / metabolism* Transposases / genetics* |
| Grant Support | |
ID/Acronym/Agency:
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CA 16672/CA/NCI NIH HHS; CA100265/CA/NCI NIH HHS; CA116127/CA/NCI NIH HHS; CA124782/CA/NCI NIH HHS; R01 CA124782-05/CA/NCI NIH HHS; R01 CA141303/CA/NCI NIH HHS; R01 CA141303-02/CA/NCI NIH HHS; R01 CA141303-03/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD19; 0/RNA, Messenger; 0/Receptors, Antigen; EC 2.7.7.-/Transposases; EC 2.7.7.-/sleeping beauty transposase, human |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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