Prime editing with modification-tolerant polymerases

WO2026055354A3PCT designated stage Publication Date: 2026-05-28UNIV OF MASSACHUSETTS
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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

Technical Problem

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.

Method used

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.

Benefits of technology

The system significantly improves editing activity and efficiency by accommodating nucleotide modifications, thereby enhancing the precision and effectiveness of genetic corrections.

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Abstract

Provided are prime editing systems with modification-tolerant polymerases and petRNAs and / or pegRNA with chemically modified primer binding sites (PBS) and / or nucleotide polymerase template (NPT).
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