Prime editing with modification-tolerant polymerases
Patent Information
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- UNIV OF MASSACHUSETTS
- Filing Date
- 2025-09-04
- Publication Date
- 2026-05-28
AI Technical Summary
Early generations of prime editors employing M-MLV RT exhibit reduced editing activity due to nucleotide modifications in the primer binding site (PBS) and reverse transcriptase template (RTT), necessitating the development of systems that better tolerate such modifications.
A prime editing system comprising a Cas9 nickase protein and a modification-tolerant nucleotide polymerase (NP) protein, along with nucleotide-modified primer binding site (PBS) and nucleotide polymerase template (NPT), and optionally a single guide RNA (sgRNA) or prime editing guide RNA (pegRNA), which includes nucleotide modifications such as ribose and phosphate group alterations, to enhance editing tolerance.
The system significantly improves editing activity and efficiency by accommodating nucleotide modifications, thereby enhancing the precision and effectiveness of genetic corrections.