Engineered prime editors with minimal genomic errors
4 hours ago
- #prime editing
- #CRISPR
- #genome editing
- Prime editors enable precise genome modifications by writing new sequences into nicked DNA 3′ ends.
- A key challenge is minimizing insertion and deletion (indel) errors, which can be unpredictable and harmful.
- Engineered Cas9-nickase mutations relax nick positioning, promoting nicked end degradation and reducing indel errors.
- A next-generation prime editor (vPE) achieves high efficiency with up to 60-fold lower indel errors compared to previous editors.
- vPE combines error-suppressing mutations with pegRNA stabilization, achieving edit:indel ratios as high as 543:1.
- The study demonstrates the effectiveness of vPE in various cell types, including HEK293T, A549, HeLa, and mouse embryonic stem cells.
- The engineered prime editors simplify genome editing by reducing the need for extensive pegRNA optimization.
- The findings suggest a new paradigm for designing genome editors with enhanced precision and efficiency.