4.3 Article

In vivo hypermutation and continuous evolution

Journal

NATURE REVIEWS METHODS PRIMERS
Volume 2, Issue 1, Pages -

Publisher

SPRINGERNATURE
DOI: 10.1038/s43586-022-00119-5

Keywords

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Funding

  1. National Institutes of Health (NIH) National Institute of General Medical Sciences (NIGMS) [1R35GM139513]
  2. NIH NIGMS [1R01GM125887]
  3. MIT School of Science Fund for Future of Science
  4. US Department of Energy, Office of Science, Basic Energy Sciences [DE-SC0020153]
  5. Innovative Genomics Institute and Laboratory for Genomics Research
  6. NIH National Institute of Biomedical Imaging and Bioengineering (NIBIB) [1R01EB027793]
  7. Department of Defense (DoD) Vannevar Bush Faculty Fellowship [N00014-20-1-2825]
  8. Ministerio de Ciencia e Innovacion -Consejo Superior de Investigaciones Cientificas (MICIN-CSIC) PTI + [REC-EU SGL2103051]
  9. EU
  10. U.S. Department of Energy (DOE) [DE-SC0020153] Funding Source: U.S. Department of Energy (DOE)

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By achieving rapid cycles of mutation, amplification, and selection fully inside living cells, genetic systems have advanced the scale, depth, and overall power of directed evolution, accessing important new areas of protein evolution and engineering.
Directed evolution has revolutionized bimolecular engineering by applying cycles of mutation, amplification and selection to genes of interest (GOIs). However, classical directed evolution methods that rely on manually staged evolutionary cycles constrain the scale and depth of the evolutionary search that is possible. We describe genetic systems that achieve cycles of rapid mutation, amplification and selection fully inside living cells, enabling the continuous evolution of GOIs as cells grow. These systems advance the scale, evolutionary search depth, ease and overall power of directed evolution and access important new areas of protein evolution and engineering.

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