Human-Derived RNA Targeting System for Reduced Immunogenicity
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Solution Overview
Problem
Current RNA-targeting systems are large in size, pose immunogenicity issues, and require continual administration, making them inefficient and potentially harmful for therapeutic applications.
Innovation Solution
A CRISPR/Cas-inspired RNA targeting system (CIRTS) that is up to 5-fold smaller than existing systems and can be engineered from human parts, delivering regulatory proteins site-selectively using Watson-Crick-Franklin base pair interactions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current RNA-targeting systems are used, then RNA modulation capability is achieved, but system size becomes large and immunogenicity issues arise
Solution Approach 1:
The system divides the RNA-targeting function into separate modular components: a small programmable protein module that binds to guide RNA and a separate effector domain. This segmentation allows the targeting mechanism to be simplified while maintaining functionality, directly addressing the issue of large system size while preserving RNA modulation capability.
Solution Approach 2:
The invention extracts and removes the microbial-derived CRISPR/Cas proteins that cause immunogenicity, replacing them with human-derived programmable proteins. This extraction eliminates the harmful immunogenic component while retaining the essential RNA-targeting and modulation functions.
2Reliability
If current RNA-targeting systems are used, then RNA modulation is achieved, but continual administration is required
Solution Approach 1:
The system enables preliminary action by allowing programming of the protein module before administration to bind specific guide RNAs. This pre-programming capability allows the system to be prepared in advance with specific targeting information, potentially reducing the need for continual re-administration by enabling long-lasting targeted modulation.
3Reliability
If current RNA-targeting systems are used, then RNA modulation is achieved, but immune response is activated
Solution Approach 1:
The invention converts the harmful immunogenicity of microbial CRISPR proteins into a benefit by using human-derived programmable proteins that do not trigger immune responses. This transformation maintains the essential RNA-targeting function while eliminating the harmful immune activation, turning a harmful characteristic into a beneficial one.
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
CIRTS efficiently modulates RNA without activating an immune response, enabling targeted RNA regulation and therapeutic interventions.
Implementation Method 1
uses Watson-Crick-Franklin base pair interactions to deliver protein cargo site-selectively in the transcriptome
Data Source
AI summary
Aspects of the disclosure relate to a Effector system comprising at least one of each: i) a RNA hairpin binding domain; ii) a RNA targeting molecule comprising a RNA targeting region and at least one hairpin structure, wherein the hairpin structure of the RNA targeting molecule specifically binds to i; and iii) a Effector domain.