Abasic CRISPR RNAs inherently harness fidelity of SpCas9 for genome editing.

Abasic modifications at the 5' end of crRNAs suppress off-target self-cleavages by activated SpCas9 in Streptococcus pyogenes while preserving on-target efficiency.

• Why it matters: Genome editing with CRISPR-Cas9 often produces deleterious off-target cleavages, limiting safe and precise applications.
• What they did: Sequencing crRNAs showed oxidative stress from bacteriophage infection preferentially oxidizes the 5' end into abasic modifications; abasic substitutions or extensions were tested for effects on base pairing and SpCas9 fidelity.
• The result: Combining 5' abasic substitution and extension increases mismatch intolerance at the PAM-distal region and improves SpCas9 fidelity, outperforming SpCas9 variants and supporting in vivo potential.

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