ArticleGenome biology2026
Directed evolution of compact RNA-guided nucleases for enhanced activity in mammalian cells.
Article in Genome biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
4 citing papers in PubMed.
- Stepwise DNA-unwinding gates TnpB genome-editing activity.Molecular cell · 2026Article
- Structure and evolution-guided design of minimal RNA-guided nucleases.Science (New York, N.Y.) · 2026Article
- Engineering TnpB as a compact RNA-guided genome editor from molecular constraints to design principles.Frontiers in genome editing · 2026Review
- Structure and evolution-guided design of minimal RNA-guided nucleases.bioRxiv : the preprint server for biology · 2025Article
Corrections and comments
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Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRNA-guided nucleases enable DNA editing and offer promise for treating genetic diseases, particularly when used for precise sequence replacement. However, many of the most effective enzymes, such as Streptococcus pyogenes Cas9, are too large for delivery using vectors like adeno-associated virus. This has prompted interest in smaller alternatives from the Cas12f and TnpB families. Yet, these nucleases often show low activity in mammalian cells, limiting their utility.
resultsWe use directed evolution in human cells to select variants with greatly improved activity. The resulting variants, Cas12f1Super and TnpBSuper, exhibit up to 11-fold increase in editing efficiency without increased off-target effects. When tested as a base editor, Cas12f1Super shows up to tenfold improvement relative to the previously engineered CasMINI, suggesting utility beyond nuclease-related activities.
conclusionsThese compact and efficient genome editors expand the current toolkit and hold promise for both research and therapeutic use in mammalian systems.
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