TraC Effector Protein CRISPR System for Compact Genome Editing
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Solution Overview
Problem
Current CRISPR gene editing systems, particularly those based on Cas12 proteins, face limitations in efficiency, specificity, and versatility for genome editing applications.
Innovation Solution
The development of a novel CRISPR system utilizing TraC effector proteins, which can form complexes with guide RNAs derived from transposon right elements or traditional CRISPR systems, enabling targeted DNA binding and cleavage with enhanced specificity and efficiency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If Cas12 proteins are used for genome editing, then DNA cleavage activity is achieved, but the protein size is large which limits delivery efficiency
Solution Approach 1:
The patent identifies and utilizes smaller Cas12 protein variants (such as Cas12f, Cas12j, and other miniaturized versions) that retain DNA cleavage functionality while having reduced molecular weights compared to traditional Cas12a/b proteins. This allows the editing machinery to be delivered more efficiently into cells while maintaining the essential nuclease activity for genome editing applications.
2Reliability
If traditional CRISPR systems are used, then genome editing capability is achieved, but versatility is limited requiring multiple different tools for different applications
Solution Approach 1:
The patent describes engineered CRISPR systems where a single Cas12 protein variant can perform multiple genome editing functions including but not limited to: precise DNA cleavage, base editing when fused with deaminase enzymes, prime editing when combined with reverse transcriptase, and transcriptional regulation. This multi-functional design allows researchers to accomplish various editing goals using a unified platform rather than requiring separate specialized tools for each application type.
3Productivity
If Cas12 proteins with multiple functional domains are used, then DNA cleavage efficiency is improved, but system complexity increases
Solution Approach 1:
The patent focuses on isolating and optimizing the essential RuvC domain functionality in Cas12 proteins, removing or simplifying non-essential functional domains that contribute to complexity. By concentrating on the core nuclease activity and using streamlined protein variants with fewer auxiliary domains, the system achieves high DNA cleavage efficiency while reducing overall system complexity and ease of manipulation.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The TraC-based CRISPR system demonstrates improved genome editing capabilities, including dual guidance mechanisms, efficient DNA cleavage, and potential for multiple genome editing applications with a single tool, while being suitable for delivery and editing in vivo due to its smaller monomeric size.
Implementation Method 1
the TraC effector protein can target and bind to a target DNA sequence under the guidance of the guide RNA
Implementation Method 2
the TraC effector protein can target and bind to a target DNA sequence... efficient DNA cleavage
Data Source
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AI summary
The present invention belongs to the field of genetic engineering. Specifically, the present invention relates to a novel CRISPR gene editing system and uses thereof. More specifically, the present invention provides a TraC (intermediates between Transposon and CRISPR-Cas12) effector protein or functional variant thereof, gene editing systems based thereon and uses thereof.