ArticleNature communications2024
Evolved cytidine and adenine base editors with high precision and minimized off-target activity by a continuous directed evolution system in mammalian cells.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- A dual A-to-Y and G-to-Y base editor and a four-base concurrent hypermutator in mammalian cells.Nature communications · 2026Article
- Pancreatic organoids and organoid-on-a-chip platforms: from disease modeling to precision therapy.Journal of translational medicine · 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
- Therapeutic adenine base editor with minimized off-target effects.Protein & cell · 2026Article
- Design of Safe and Efficient Adenine Base Editors via Protein Language Model Screening for Osteoarthritis Treatment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Engineering Compact Base Editors by AlphaFold-Guided Mutation Scan and Escherichia coli-Based Tri-Selection.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- ABE9 fused to SpRY Cas9 nickase enables precise generation of bystander free mouse models.Scientific reports · 2026Article
- Chemical control of 2'-hydroxyl-dependent Cas9 target engagement enables CRISPR RNA ribose replacement.bioRxiv : the preprint server for biology · 2026Article
- Engineered base editors with reduced bystander editing through directed evolution.Nature biotechnology · 2025Article
- Anti-CRISPR-mediated continuous directed evolution of CRISPR-Cas9 in human cells.bioRxiv : the preprint server for biology · 2025Article
- Adenine base editor correction of pathogenic variations associated with inherited retinal dystrophy in patient iPSC and retinal organoids.Molecular therapy. Nucleic acids · 2025Article
- Efforts to Downsize Base Editors for Clinical Applications.International journal of molecular sciences · 2025Review
- Harnessing mass spectrometry-based proteomics for continuous directed evolution.Synthetic biology (Oxford, England) · 2025Article
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Authors and funding
15 authors.
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Abstract
Continuous directed evolution of base editors (BEs) has been successful in bacteria cells, but not yet in mammalian cells. Here, we report the development of a Continuous Directed Evolution system in Mammalian cells (CDEM). CDEM enables the BE evolution in a full-length manner with Cas9 nickase. We harness CDEM to evolve the deaminases of cytosine base editor BE3 and adenine base editors, ABEmax and ABE8e. The evolved cytidine deaminase variants on BE4 architecture show not only narrowed editing windows, but also higher editing purity and low off-target activity without a trade-off in on-targeting activity. The evolved ABEmax and ABE8e variants exhibit narrowed or shifted editing windows to different extents, and lower off-target effects. The results illustrate that CDEM is a simple but powerful approach to continuously evolve BEs without size restriction in the mammalian environment, which is advantageous over continuous directed evolution system in bacteria cells.
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