Engineered CasX systems

CasX variants with modified domains and guide nucleic acids enhance gene editing efficiency by up to 81-fold, addressing the need for improved Class 2 CRISPR/Cas systems for therapeutic and research applications.

AU2020289591B2Pending Publication Date: 2026-07-23SCRIBE THERAPEUTICS INC
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Patent Information

Application Number
AU2020289591
Authority / Receiving Office
AU · AU
Patent Type
Applications
Current Assignee / Owner
Priority Date
2020-05-27
Filing Date
2020-06-05
Publication Date
2026-07-23
Estimated Expiration
2040-06-05

AI Technical Summary

Technical Problem

There is a need for additional Class 2 CRISPR/Cas systems that have been optimized and/or offer improvements over earlier generation systems for utilization in therapeutic, diagnostic, and research applications.

Method used

Development of CasX variants with modified domains such as NTSB, TSL, helical I, helical II, OBD, and RuvC domains, and guide nucleic acids with modified regions like extended stem loops and triplexes, which form complexes to bind target DNA and enhance editing efficiency.

Benefits of technology

The CasX variants exhibit improved gene editing capabilities, achieving up to 81-fold enhancement in editing efficiency compared to reference systems, and can edit both canonical and non-canonical PAMs effectively.

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Abstract

Provided herein are engineered CasX systems and components thereof, including variant CasX proteins and variant guide nucleic acids (gNAs). The variant CasX proteins and variant gNAs of the disclosure display at least one improved characteristic when compared to a reference CasX protein or reference gNA of the disclosure. In some instances, the variants have one or more improved CasX ribonucleoprotein complex functions. Also provided are methods of making and using said variants.
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