Biotechnology advancesFeb 4, 2026

Improving the accuracy and success of prime editing

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗

Updated Feb 5, 2026

Abstract

Prime editing enables precise genetic modifications without introducing double-strand breaks or donor DNA templates.

The efficiency of prime editing varies significantly across different genomic contexts.
Protein engineering has produced editor variants with improved reverse transcriptase activity and stability.
Optimized pegRNA designs enhance functional integrity and resistance to degradation.
Regulating the PE-Flap-mismatch repair process helps retain desired genetic edits.
Development of PAM-relaxed Cas variants increases the number of targetable sites.

Simplified

Prime editing (PE) enables the precise installation of targeted insertions, deletions, and all possible base-to-base conversions without introducing double-strand breaks or donor DNA templates. However, its efficiency remains highly variable across genomic contexts. To address this, multi-faceted optimization strategies have been developed: protein engineering has yielded editor variants with enhanced reverse transcriptase activity and stability; structural refinements to pegRNA design improve its functional integrity and resistance to degradation; regulation of the PE-Flap-mismatch repair (MMR) process favors the retention of desired edits; and the development of protospacer adjacent motif (PAM)-relaxed Cas variants dramatically expands targetable sites. This review systematically consolidates these advances, illustrating how the integration of structural, mechanistic and targeting enhancements is overcoming fundamental bottlenecks. Together, these developments establish PE as a versatile and efficient system for precision genome engineering, paving the way for its reliable application in diverse biological settings.

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Improving the accuracy and success of prime editing

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