ArticleNature chemical biology2025
Orthogonal RNA replication enables directed evolution and Darwinian adaptation in mammalian cells.
Article in Nature chemical biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Harnessing the central dogma: Enzyme-driven gene diversification strategies for in cellulo continuous directed evolution.Fundamental research · 2026Review
- Next-generation programmable cell therapies for precision medicine.Nature reviews. Genetics · 2026Review
- Anti-CRISPR-mediated continuous directed evolution of CRISPR-Cas9 in human cells.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Anti-CRISPR-mediated continuous directed evolution of CRISPR-Cas9 in human cells.bioRxiv : the preprint server for biology · 2025Article
- Editor's Choice Protein engineering strategies to develop lectins by design.Glycobiology · 2025Review
- A chimeric viral platform for directed evolution in mammalian cells.Nature communications · 2025Article
- Nickase fidelity drives EvolvR-mediated diversification in mammalian cells.Nature communications · 2025Article
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
Directed evolution in mammalian cells offers a powerful approach for advancing synthetic biology applications. However, existing mammalian-based directed evolution methods face substantial bottlenecks, including host genome interference, small library size and uncontrolled mutagenesis. Here we engineered an orthogonal alphaviral RNA replication system to evolve RNA-based devices, enabling RNA replicase-assisted continuous evolution (REPLACE) in proliferating mammalian cells. This system generates a large, continuously diversified library of replicative RNAs through replicase-limited mode of replication and inducible mutagenesis. Using REPLACE, we engineered fluorescent proteins and transcription factors. Notably, cells equipped with REPLACE can undergo Darwinian adaptation, allowing them to evolve in response to both cell-extrinsic and cell-intrinsic challenges. Collectively, this work establishes a powerful platform for advancing mammalian synthetic biology and cell engineering applications through directed evolution.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.