Mechanogenetics for the remote and noninvasive control of cancer immunotherapy Journal Article
| Authors: | Pan, Y.; Yoon, S.; Sun, J.; Huang, Z.; Lee, C.; Allen, M.; Wu, Y.; Chang, Y. J.; Sadelain, M.; Shung, K. K.; Chien, S.; Wang, Y. |
| Article Title: | Mechanogenetics for the remote and noninvasive control of cancer immunotherapy |
| Abstract: | While cell-based immunotherapy, especially chimeric antigen receptor (CAR)-expressing T cells, is becoming a paradigm-shifting therapeutic approach for cancer treatment, there is a lack of general methods to remotely and noninvasively regulate genetics in live mammalian cells and animals for cancer immunotherapy within confined local tissue space. To address this limitation, we have identified a mechanically sensitive Piezo1 ion channel (mechanosensor) that is activatable by ultrasound stimulation and integrated it with engineered genetic circuits (genetic transducer) in live HEK293T cells to convert the ultrasound-activated Piezo1 into transcriptional activities. We have further engineered the Jurkat T-cell line and primary T cells (peripheral blood mononuclear cells) to remotely sense the ultrasound wave and transduce it into transcriptional activation for the CAR expression to recognize and eradicate target tumor cells. This approach is modular and can be extended for remote-controlled activation of different cell types with high spatiotemporal precision for therapeutic applications. |
| Keywords: | controlled study; protein expression; unclassified drug; human cell; cancer immunotherapy; gene expression; transcription initiation; ultrasound; chimeric antigen receptor; peripheral blood mononuclear cell; gene technology; synthetic biology; ion channel; human; priority journal; article; mechanical stimulation; hek293t cell line; mechanogenetics; remote control; piezo1 ion channel; jurkat cell line; remote controlled mechanogenetics |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 115 |
| Issue: | 5 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2018-01-30 |
| Start Page: | 992 |
| End Page: | 997 |
| Language: | English |
| DOI: | 10.1073/pnas.1714900115 |
| PROVIDER: | scopus |
| PMCID: | PMC5798350 |
| PUBMED: | 29343642 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 March 2018 -- Source: Scopus |
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