A synthetic transcription platform for programmable gene expression in mammalian cells
<jats:title>Abstract</jats:title><jats:p>Precise, scalable, and sustainable control of genetic and cellular activities in mammalian cells is key to developing precision therapeutics and smart biomanufacturing. Here we create a highly tunable, modular, versatile CRISPR-based synthet...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Springer Science and Business Media LLC
2023
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| Online Access: | https://hdl.handle.net/1721.1/147941 |
| _version_ | 1811089702857474048 |
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| author | Chen, William CW Gaidukov, Leonid Lai, Yong Wu, Ming-Ru Cao, Jicong Gutbrod, Michael J Choi, Gigi CG Utomo, Rachel P Chen, Ying-Chou Wroblewska, Liliana Kellis, Manolis Zhang, Lin Weiss, Ron Lu, Timothy K |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Chen, William CW Gaidukov, Leonid Lai, Yong Wu, Ming-Ru Cao, Jicong Gutbrod, Michael J Choi, Gigi CG Utomo, Rachel P Chen, Ying-Chou Wroblewska, Liliana Kellis, Manolis Zhang, Lin Weiss, Ron Lu, Timothy K |
| author_sort | Chen, William CW |
| collection | MIT |
| description | <jats:title>Abstract</jats:title><jats:p>Precise, scalable, and sustainable control of genetic and cellular activities in mammalian cells is key to developing precision therapeutics and smart biomanufacturing. Here we create a highly tunable, modular, versatile CRISPR-based synthetic transcription system for the programmable control of gene expression and cellular phenotypes in mammalian cells. Genetic circuits consisting of well-characterized libraries of guide RNAs, binding motifs of synthetic operators, transcriptional activators, and additional genetic regulatory elements express mammalian genes in a highly predictable and tunable manner. We demonstrate the programmable control of reporter genes episomally and chromosomally, with up to 25-fold more activity than seen with the EF1α promoter, in multiple cell types. We use these circuits to program the secretion of human monoclonal antibodies and to control T-cell effector function marked by interferon-γ production. Antibody titers and interferon-γ concentrations significantly correlate with synthetic promoter strengths, providing a platform for programming gene expression and cellular function in diverse applications.</jats:p> |
| first_indexed | 2024-09-23T14:23:21Z |
| format | Article |
| id | mit-1721.1/147941 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T14:23:21Z |
| publishDate | 2023 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1479412023-02-08T03:14:32Z A synthetic transcription platform for programmable gene expression in mammalian cells Chen, William CW Gaidukov, Leonid Lai, Yong Wu, Ming-Ru Cao, Jicong Gutbrod, Michael J Choi, Gigi CG Utomo, Rachel P Chen, Ying-Chou Wroblewska, Liliana Kellis, Manolis Zhang, Lin Weiss, Ron Lu, Timothy K Massachusetts Institute of Technology. Department of Biological Engineering <jats:title>Abstract</jats:title><jats:p>Precise, scalable, and sustainable control of genetic and cellular activities in mammalian cells is key to developing precision therapeutics and smart biomanufacturing. Here we create a highly tunable, modular, versatile CRISPR-based synthetic transcription system for the programmable control of gene expression and cellular phenotypes in mammalian cells. Genetic circuits consisting of well-characterized libraries of guide RNAs, binding motifs of synthetic operators, transcriptional activators, and additional genetic regulatory elements express mammalian genes in a highly predictable and tunable manner. We demonstrate the programmable control of reporter genes episomally and chromosomally, with up to 25-fold more activity than seen with the EF1α promoter, in multiple cell types. We use these circuits to program the secretion of human monoclonal antibodies and to control T-cell effector function marked by interferon-γ production. Antibody titers and interferon-γ concentrations significantly correlate with synthetic promoter strengths, providing a platform for programming gene expression and cellular function in diverse applications.</jats:p> 2023-02-07T18:30:45Z 2023-02-07T18:30:45Z 2022 2023-02-07T18:24:05Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/147941 Chen, William CW, Gaidukov, Leonid, Lai, Yong, Wu, Ming-Ru, Cao, Jicong et al. 2022. "A synthetic transcription platform for programmable gene expression in mammalian cells." Nature Communications, 13 (1). en 10.1038/S41467-022-33287-9 Nature Communications Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Springer Science and Business Media LLC Nature |
| spellingShingle | Chen, William CW Gaidukov, Leonid Lai, Yong Wu, Ming-Ru Cao, Jicong Gutbrod, Michael J Choi, Gigi CG Utomo, Rachel P Chen, Ying-Chou Wroblewska, Liliana Kellis, Manolis Zhang, Lin Weiss, Ron Lu, Timothy K A synthetic transcription platform for programmable gene expression in mammalian cells |
| title | A synthetic transcription platform for programmable gene expression in mammalian cells |
| title_full | A synthetic transcription platform for programmable gene expression in mammalian cells |
| title_fullStr | A synthetic transcription platform for programmable gene expression in mammalian cells |
| title_full_unstemmed | A synthetic transcription platform for programmable gene expression in mammalian cells |
| title_short | A synthetic transcription platform for programmable gene expression in mammalian cells |
| title_sort | synthetic transcription platform for programmable gene expression in mammalian cells |
| url | https://hdl.handle.net/1721.1/147941 |
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