Endogenous Gag Capsids for Precise Nucleic Acid Delivery
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Solution Overview
Problem
Current methods for delivering nucleic acids to cells face limitations such as immunogenicity, limited payload capacity, poor bio-distribution, and off-target effects, necessitating the development of new approaches for precise and efficient therapeutic delivery.
Innovation Solution
The use of recombinant and engineered Arc and endogenous Gag polypeptides to form capsids that can encapsulate and deliver therapeutic agents, such as RNA, to specific sites within cells, leveraging their ability to assemble into capsids for targeted cargo delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current methods for delivering nucleic acids to cells are used, then delivery can be achieved, but immunogenicity occurs and off-target effects are caused
Solution Approach 1:
The patent uses endogenous Gag polypeptides as intermediary carriers to deliver therapeutic nucleic acids. These polypeptides form capsids that serve as mediators between the therapeutic agent and target cells, enabling precise delivery while reducing immunogenicity and off-target effects compared to traditional viral vectors
Solution Approach 2:
The patent modifies parameters of the delivery system by using recombinant and engineered Arc and endogenous Gag polypeptides with specific amino acid sequences (SEQ ID NO: 1-28). These parameter changes in polypeptide structure enable controlled capsid formation with optimized delivery properties, reducing harmful effects while maintaining delivery precision
2Quantity of substance
If current nucleic acid delivery methods are used, then delivery can be achieved, but payload capacity is limited
Solution Approach 1:
The patent employs a nested structure where therapeutic nucleic acids are encapsulated within capsids formed by endogenous Gag polypeptides. This nesting approach allows the capsid to protect and deliver larger payload capacities while maintaining delivery efficiency through the polypeptide's natural cellular interaction mechanisms
3Reliability
If current delivery methods are used, then nucleic acids can be delivered to cells, but bio-distribution is poor
Solution Approach 1:
The endogenous Gag polypeptides possess multi-functional capabilities: they can self-assemble into capsids, interact with cellular machinery for targeted delivery, and provide protective encapsulation. This universality enables improved bio-distribution across different cell types while maintaining delivery accuracy through the polypeptides' inherent cellular recognition properties
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
This approach enables precise and efficient delivery of therapeutic agents to cells, reducing off-target effects and improving bio-distribution, while allowing for the modification of cargo binding domains to enhance loading capabilities.
Implementation Method 1
leveraging their ability to assemble into capsids for targeted cargo delivery
Data Source
AI summary
Nucleic acids encoding endogenous Gag peptides can be isolated from various organisms. Nucleic acids encoding various endogenous Gag polypeptides can be isolated from human DNA. The nucleic acids can be used to express endogenous Gag polypeptides that can be assembled into capsids. Endogenous Gag polypeptides and capsids can be used package cargo and/or deliver it to cells, for example, to package and/or deliver a nucleic acid molecule for use in gene editing, such as a component involved in a CRISPR-Cas system.