Evolved adenine deaminase and RNA-guided nuclease fusion proteins with internal insertion sites and methods of use

By inserting deaminase peptides into RNA-guided nucleases to form fusion proteins, the problems of low editing efficiency and limited editing window of existing RNA-guided nucleases have been solved, achieving more efficient genome editing that is applicable to gene function research, treatment of hereditary diseases, and agricultural biotechnology.

CN121127583APending Publication Date: 2025-12-12LIFEEDIT THERAPEUTICS INC
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Patent Information

Application Number
CN202380090553.8
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Priority Date
2023-02-17
Filing Date
2023-11-06
Publication Date
2025-12-12

AI Technical Summary

Technical Problem

Existing RNA-guided nuclease systems suffer from low editing efficiency and limited editing windows in genome editing, making it difficult to efficiently modify specific genomic locations.

Method used

By designing a fusion protein containing RNA-guided nuclease and deaminase peptides, and inserting heterologous peptides into the RNA-guided nuclease, a base editor is formed, improving editing activity and editing window.

Benefits of technology

It enables more efficient genome editing, expands the editing window, and improves the ability to modify specific genomic locations, making it suitable for gene function research, treatment of hereditary diseases, and agricultural biotechnology.

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Abstract

Compositions and methods comprising a deaminase for targeted editing of nucleic acids are provided. Also provided are compositions and methods for localizing a heterologous polypeptide to a target DNA molecule, and compositions and methods for targeted editing of nucleic acids. Fusion proteins comprising an RNA-guided nuclease (RGN) and at least one heterologous polypeptide inserted therein are provided, as well as fusion proteins comprising a DNA binding polypeptide and a deaminase. The heterologous polypeptide may be a pilot editing polypeptide or a base editing polypeptide. Compositions also include nucleic acid molecules encoding a deaminase or fusion protein. Vectors and host cells comprising the nucleic acid molecules encoding the deaminase or fusion protein are also provided.
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