Abstract
Directed evolution experiments are typically carried out using in vitro systems, bacteria, or yeast—even when the goal is to probe or modulate mammalian biology. Performing directed evolution in systems that do not match the intended mammalian environment severely constrains the scope and functionality of the targets that can be evolved. We review new platforms that are now making it possible to use the mammalian cell itself as the setting for directed evolution and present an overview of frontier challenges and high-impact targets for this approach.
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Acknowledgements
S.J.H. acknowledges support from the National Science Foundation Graduate Research Fellowship Program under grant no. 1745302. M.D.S. acknowledges support from the National Institutes of Health, National Institute of General Medical Sciences (1R35GM136354).
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S.J.H. and M.D.S. wrote and revised the manuscript.
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S.J.H. and M.D.S. are co-inventors on a patent application filed by MIT related to the use of adenoviruses for mammalian cell-based directed evolution. M.D.S. is a co-inventor on a patent application filed by MIT related to the MutaT7 system.
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Hendel, S.J., Shoulders, M.D. Directed evolution in mammalian cells. Nat Methods 18, 346–357 (2021). https://doi.org/10.1038/s41592-021-01090-x
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DOI: https://doi.org/10.1038/s41592-021-01090-x
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