High-fidelity CRISPR–Cas9 enzymes have fewer off-targets but often suffer from low editing efficiency. Here, we show that a simple extension of the guide RNA improves the activity of SuperFi-Cas9 while preserving its accuracy. This extension enhances SuperFi-Cas9’s genome editing performance by strengthening the interactions in the protospacer adjacent motif (PAM)-distal region.
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References
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This is a summary of: Zheng, R. et al. Improving the efficiency of high-fidelity Cas9 by enhancing PAM-distal interactions. Nat. Struct. Mol. Biol. https://doi.org/10.1038/s41594-026-01753-3 (2026).
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Extending guide RNA length restores high-fidelity CRISPR–Cas9 activity. Nat Struct Mol Biol (2026). https://doi.org/10.1038/s41594-026-01765-z
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DOI: https://doi.org/10.1038/s41594-026-01765-z
