Engineered Nucleic Acid-Guided Nuclease Systems
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Solution Overview
Problem
Existing nucleic acid-guided nucleases face limitations such as sequence specificity requirements, expression issues, and delivery challenges, which restrict their applicability in genome engineering.
Innovation Solution
Development of non-naturally occurring nucleic acid-guided nuclease systems, engineered to address expression and delivery challenges, and optimized for improved target recognition and editing efficiency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If natural nucleic acid-guided nucleases are used, then the system is biocompatible and easy to deliver, but sequence specificity requirements and expression issues limit applicability
Solution Approach 1:
The patent applies parameter changes by modifying the nuclease protein sequence (e.g., changing amino acid residues at specific positions) to alter its properties. This allows the nuclease to overcome sequence specificity requirements and expand applicability to different target sequences while maintaining reliability through controlled modifications.
Solution Approach 2:
The patent creates composite systems by combining engineered nucleases with various guide nucleic acids (crRNA, tracrRNA, or synthetic guides). This composite approach allows the system to adapt to different target sequences and genomic locations, improving versatility while maintaining functional reliability through the synergistic interaction of components.
2Productivity
If existing nucleic acid-guided nucleases are used, then the basic editing function is achieved, but delivery and expression challenges limit effectiveness
Solution Approach 1:
The patent applies local quality by optimizing specific regions of the nuclease protein and guide nucleic acid for improved delivery and expression. This includes modifying specific amino acid sequences to enhance protein stability, adding localization signals for targeted delivery to specific cellular compartments, and optimizing guide RNA structures for efficient processing and function.
Solution Approach 2:
The patent uses intermediary elements such as viral vectors, plasmids, or lipid nanoparticles as mediators to facilitate delivery of the nuclease system into cells. These intermediaries overcome delivery challenges by providing protected transport mechanisms, while expression is enhanced through optimized promoter sequences and regulatory elements in the delivery vehicle.
3Adaptability or versatility
If engineered nucleic acid-guided nucleases are developed to overcome limitations, then applicability is improved, but system complexity increases
Solution Approach 1:
The patent applies segmentation by dividing the genome editing system into separate functional modules: the nuclease protein, guide nucleic acid, and target sequence. This modular approach allows independent optimization of each component to overcome sequence specificity limitations while maintaining manageable system complexity through clear functional separation.
Solution Approach 2:
The patent creates universal nuclease systems that can target multiple different sequences through a single engineered nuclease protein combined with interchangeable guide nucleic acids. This multi-functionality approach improves adaptability across different genomic targets while controlling complexity by reusing the same nuclease backbone with varying guides.
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 engineered nucleic acid-guided nuclease systems enhance genome editing efficiency, overcome sequence specificity limitations, and improve delivery and expression, making them more effective tools for genome engineering.
Implementation Method 1
an engineered guide nucleic acid capable of complexing with the nucleic acid-guided nuclease
Data Source
AI summary
Disclosed herein are nucleic acid-guided nucleases, guide nucleic acids, and targetable nuclease systems, and methods of use. Disclosed herein are engineered non-naturally occurring nucleic acid-guided nucleases, guide nucleic acids, and targetable nuclease systems, and methods of use. Targetable nuclease systems can be used to edit genetic targets, including recursive genetic engineering and trackable genetic engineering methods.