Academic Journal
Characterizing piggyBat—a transposase for genetic modification of T cells
| Title: | Characterizing piggyBat—a transposase for genetic modification of T cells |
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| Authors: | Gaurav Sutrave, Ning Xu, Tiffany C.Y. Tang, Alla Dolnikov, Brian Gloss, David J. Gottlieb, Kenneth P. Micklethwaite, Kavitha Gowrishankar |
| Source: | Molecular Therapy: Methods & Clinical Development, Vol 25, Iss , Pp 250-263 (2022) |
| Publisher Information: | Elsevier, 2022. |
| Publication Year: | 2022 |
| Collection: | LCC:Genetics LCC:Cytology |
| Subject Terms: | chimeric antigen receptor, CAR, transposons, non-viral vector, piggybat, T cell immunotherapy, Genetics, QH426-470, Cytology, QH573-671 |
| More Details: | Chimeric antigen receptor (CAR) T cells targeting CD19 have demonstrated remarkable efficacy in the treatment of B cell malignancies. Current CAR T cell manufacturing protocols are complex and costly due to their reliance on viral vectors. Non-viral systems of genetic modification, such as with transposase and transposon systems, offer a potential streamlined alternative for CAR T cell manufacture and are currently being evaluated in clinical trials. In this study, we utilized the previously described transposase from the little brown bat, designated piggyBat, for production of CD19-specific CAR T cells. PiggyBat demonstrates efficient CAR transgene delivery, with a relatively low variability in integration copy number across a range of manufacturing conditions as well as a similar integration site profile to super-piggyBac transposon and viral vectors. PiggyBat-generated CAR T cells demonstrate CD19-specific cytotoxic efficacy in vitro and in vivo. These data demonstrate that alternative, naturally occurring DNA transposons can be efficiently re-tooled to be exploited in real-world applications. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2329-0501 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2329050122000420; https://doaj.org/toc/2329-0501 |
| DOI: | 10.1016/j.omtm.2022.03.012 |
| Access URL: | https://doaj.org/article/3c81a532e7eb410fa741a50dda3035f5 |
| Accession Number: | edsdoj.3c81a532e7eb410fa741a50dda3035f5 |
| Database: | Directory of Open Access Journals |
| ISSN: | 23290501 |
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| DOI: | 10.1016/j.omtm.2022.03.012 |
| Published in: | Molecular Therapy: Methods & Clinical Development |
| Language: | English |