Remote Control of Mammalian Cells with Heat-Triggered Gene Switches and Photothermal Pulse Trains
- Ian C. MillerIan C. MillerThe Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia 30332, United StatesMore by Ian C. Miller,
- Marielena Gamboa CastroMarielena Gamboa CastroThe Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia 30332, United StatesMore by Marielena Gamboa Castro,
- Joe MaenzaJoe MaenzaThe Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia 30332, United StatesMore by Joe Maenza,
- Jason P. WeisJason P. WeisThe Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia 30332, United StatesMore by Jason P. Weis, and
- Gabriel A. Kwong*Gabriel A. Kwong*Phone: 404-385-3746. E-mail: [email protected]The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia 30332, United StatesInstitute for Electronics and Nanotechnology, Georgia Institute of Technology, Atlanta, Georgia 30332, United StatesParker H. Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia 30332, United StatesIntegrated Cancer Research Center, Georgia Institute of Technology, Atlanta, Georgia 30332, United StatesGeorgia Immunoengineering Consortium, Emory University and Georgia Institute of Technology, Atlanta, Georgia 30332, United StatesMore by Gabriel A. Kwong
Abstract
Engineered T cells are transforming broad fields in biomedicine, yet our ability to control cellular activity at specific anatomical sites remains limited. Here we engineer thermal gene switches to allow spatial and remote control of transcriptional activity using pulses of heat. These gene switches are constructed from the heat shock protein HSP70B′ (HSPA6) promoter, show negligible basal transcriptional activity, and activate within an elevated temperature window of 40–45 °C. Using engineered Jurkat T cells implanted in vivo, we use plasmonic photothermal heating to trigger gene expression at specific sites to levels greater than 200-fold. We show that delivery of heat as thermal pulse trains significantly increase cellular thermal tolerance compared to continuous heating curves with identical area-under-the-curve (AUC), enabling long-term control of gene expression in Jurkat T cells. This approach expands the toolkit of remotely controlled genetic devices for basic and translational applications in synthetic immunology.
Cited By
This article is cited by 4 publications.
- Lena Gamboa, Erick V. Phung, Haoxin Li, Jared P. Meyers, Anna C. Hart, Ian C. Miller, Gabriel A. Kwong. Heat-Triggered Remote Control of CRISPR-dCas9 for Tunable Transcriptional Modulation. ACS Chemical Biology 2020, 15 (2) , 533-542. https://doi.org/10.1021/acschembio.9b01005
- Peiyuan Kang, Xiaoqing Li, Yaning Liu, Stephanie I. Shiers, Hejian Xiong, Monica Giannotta, Elisabetta Dejana, Theodore John Price, Jaona Randrianalisoa, Steven O. Nielsen, Zhenpeng Qin. Transient Photoinactivation of Cell Membrane Protein Activity without Genetic Modification by Molecular Hyperthermia. ACS Nano 2019, 13 (11) , 12487-12499. https://doi.org/10.1021/acsnano.9b01993
- Brock Doiron, Mónica Mota, Matthew P. Wells, Ryan Bower, Andrei Mihai, Yi Li, Lesley F. Cohen, Neil McN. Alford, Peter K. Petrov, Rupert F. Oulton, Stefan A. Maier. Quantifying Figures of Merit for Localized Surface Plasmon Resonance Applications: A Materials Survey. ACS Photonics 2019, 6 (2) , 240-259. https://doi.org/10.1021/acsphotonics.8b01369
- Shreyas N. Dahotre, Yun Min Chang, Anna M. Romanov, Gabriel A. Kwong. DNA-Barcoded pMHC Tetramers for Detection of Single Antigen-Specific T Cells by Digital PCR. Analytical Chemistry 2019, 91 (4) , 2695-2700. https://doi.org/10.1021/acs.analchem.8b04153