In vivo hypermutation and continuous evolution

Rosana S. Molina, Gordon Rix, Amanuella A. Mengiste, Beatriz Álvarez, Daeje Seo, Haiqi Chen, Juan E. Hurtado, Qiong Zhang, Jorge Donato García-García, Zachary J. Heins, Patrick J. Almhjell, Frances H. Arnold, Ahmad S. Khalil, Andrew D. Hanson, John E. Dueber, David V. Schaffer, Fei Chen, Seokhee Kim, Luis Ángel Fernández, Matthew D. ShouldersChang C. Liu

Research output: Contribution to journalReview articlepeer-review

2 Scopus citations

Abstract

Directed evolution has revolutionized biomolecular 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.

Original languageEnglish (US)
Article number36
JournalNature Reviews Methods Primers
Volume2
Issue number1
DOIs
StatePublished - Dec 2022

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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