Engineered CRISPR-Cas Enzymes for Modular DNA Targeting
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Solution Overview
Problem
Current CRISPR-Cas systems lack additional programmable effectors and systems for modifying nucleic acids beyond their current capabilities, limiting their applications in genome and epigenome manipulation.
Innovation Solution
Development of engineered, non-naturally occurring Class 2 CRISPR-Cas systems with novel enzymes and components, including CRISPR-associated proteins and RNA guides, capable of DNA/RNA editing, insertion, excision, and mobilization, with unique domain organizations and smaller sizes for versatile delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If existing CRISPR-Cas systems are used, then genome editing capability is provided, but the diversity of programmable effectors is limited
Solution Approach 1:
The patent segments the CRISPR system into modular components: separate CRISPR RNA (crRNA) and trans-activating CRISPR RNA (tracrRNA) elements, and divides the Cas protein into distinct functional domains. This segmentation allows for greater versatility in designing different effector systems while maintaining manageable complexity through standardized modular interfaces.
Solution Approach 2:
The patent creates universal CRISPR-Cas platform components that can be adapted across multiple effector systems. The standardized crRNA and tracrRNA structures, along with conserved Cas protein domains, serve as universal elements that can be combined with different effector proteins to generate diverse programmable systems for various genome editing applications.
2Adaptability or versatility
If additional novel effectors are developed, then application scope in genome manipulation is expanded, but the component set complexity increases
Solution Approach 1:
The patent extracts and isolates specific functional domains from complex natural CRISPR systems, particularly the essential crRNA-tracrRNA-Cas protein interaction core. By extracting these minimal essential components, the patent reduces the complexity burden of additional effectors while preserving their application scope through standardized interaction interfaces.
Solution Approach 2:
The patent utilizes parameter changes in the CRISPR components, such as varying the spacer sequence length, modifying PAM sequence requirements, and adjusting protein domain compositions. These parameter variations allow development of diverse effectors with different application scopes while maintaining a consistent core component architecture, thereby managing overall system complexity.
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
Enables specific, programmed perturbations in genome and epigenome manipulation, providing additional features such as genotype-triggered cellular processes and programmable RNA-guided DNA targeting, enhancing applications in biotechnology and therapeutics.
Implementation Method 1
an RNA guide capable of hybridizing to a target nucleic acid... the CRISPR-associated protein is capable of binding to the RNA guide and of targeting the target nucleic acid sequence complementary to the spacer sequence
Data Source
AI summary
The disclosure describes novel systems, methods, and compositions for the manipulation of nucleic acids in a targeted fashion. The disclosure describes non-naturally occurring, engineered CRISPR-Cas systems, components, and methods for targeted modification of nucleic acids such as DNA. Each system includes one or more protein components and one or more nucleic acid components that together target nucleic acids.