Document Detail


The hyperactive Sleeping Beauty transposase SB100X improves the genetic modification of T cells to express a chimeric antigen receptor.
MedLine Citation:
PMID:  21451576     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
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:
Title:  Gene therapy     Volume:  18     ISSN:  1476-5462     ISO Abbreviation:  Gene Ther.     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-09-08     Completed Date:  2012-01-09     Revised Date:  2013-04-15    
Medline Journal Info:
Nlm Unique ID:  9421525     Medline TA:  Gene Ther     Country:  England    
Other Details:
Languages:  eng     Pagination:  849-56     Citation Subset:  IM    
Affiliation:
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.
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MeSH Terms
Descriptor/Qualifier:
Antigens, CD19 / 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:
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:
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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