PE3 Prime Editor
Architecture
PE2 system plus secondary sgRNA that nicks non-edited strand. Dual nicking biases repair toward edited strand. Requires two guide RNAs: pegRNA and nicking sgRNA (ngRNA).
Capabilities
Same editing scope as PE2 (all substitutions, insertions, deletions) with enhanced efficiency. Particularly improves edits that generate mismatches in non-edited strand.
Efficiency Features
Dual-guide system improves efficiency 2-5 fold for many edits. ngRNA placement requires optimization. PE3b variant nicks only after successful prime editing, reducing indels.
Characteristics
Enhanced prime editing through coordinated dual nicking. Nicking non-edited strand 50-100 bp from pegRNA protospacer increases editing 1.5-4×. Higher efficiency but slightly increased indel byproducts (10-20%) versus PE2. Balance of efficiency and precision.
Literature References
- Anzalone et al. (2019). Search-and-replace genome editing without double-strand breaks or donor DNA. Nature - Anzalone 2019 Prime Editing
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