A synthetic transcription platform for programmable gene expression in mammalian cells
Name
s41467-022-33287-9.pdf
Description
Published version
Size
2.46 MB
Format
Adobe PDF
Checksum (MD5)
c3bc121cf4fb7e650f5209b561683ec3
Author(s)
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
Date Issued
2022
Journal
Nature Communications
Publisher
Springer Science and Business Media LLC
Citation
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).
Version
Final published version
Abstract
AbstractPrecise, 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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1038/S41467-022-33287-9
