RAFT Polymer Nanoparticles for Large-Payload Non-Viral Delivery
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Solution Overview
Problem
Current gene delivery systems, including adeno-associated viruses (AAVs) and non-viral systems like liposomes, face challenges in delivering large genetic payloads or multiple payloads to specific tissues while avoiding immune responses and ensuring stability, as they are prone to degradation and lack effective targeting capabilities.
Innovation Solution
Development of biocompatible polymer nanoparticle and DNA nanostructure compositions, such as RAFT polymer and DNA origami, which can be programmed for immune evasion, targeted delivery, and stability, enabling the delivery of large genetic payloads or multiple payloads.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If adeno-associated viruses (AAVs) are used for genetic medicine delivery, then delivery efficiency to specific tissues is improved, but the ability to deliver large genetic payloads or multiple payloads is lost and immune responses are triggered
Solution Approach 1:
The patent segments the delivery system into multiple components: a virus-like particle core that provides targeted delivery and a separate programmable DNA/RNA component that provides adaptability. The VLP can be engineered with specific capsid proteins for tissue targeting, while the DNA/RNA payload can be independently designed to carry various genetic medicines including large payloads that would not fit in traditional AAV vectors.
Solution Approach 2:
The patent creates a composite delivery system combining virus-like particle structures with programmable nucleic acid components. The VLP core provides the biological functionality for cellular entry and targeting, while the engineered DNA/RNA components provide the flexible payload capacity. This composite approach allows the system to overcome the limitations of both traditional viral vectors and synthetic carriers.
2Reliability
If adeno-associated viruses (AAVs) are used for genetic medicine delivery, then targeted delivery to specific tissues is achieved, but unwanted immune responses including anti-AAV antibodies are generated
Solution Approach 1:
The patent extracts the immunogenic components from the delivery system by using virus-like particles that lack viral genetic material. The VLPs are engineered to contain only the structural proteins necessary for targeted delivery and cellular entry, while the therapeutic payload is delivered as separate DNA/RNA components. This separation removes the triggers for strong immune responses while preserving the targeting functionality.
Solution Approach 2:
The patent uses virus-like particles as intermediary structures that mediate between the need for targeted delivery and the need to avoid immune responses. The VLPs provide the biological recognition and cellular entry functions of viral vectors but are engineered to be immunologically quieter by lacking complete viral genomes and incorporating modified capsid proteins that reduce immunogenicity.
3Object-affected harmful factors
If non-viral gene delivery systems like liposomes are used, then immune evasion is achieved, but biocompatibility is poor and enzymatic degradation occurs
Solution Approach 1:
The patent creates a composite system that combines the biocompatibility of synthetic carriers with the biological functionality of viral vectors. The virus-like particle structure provides enhanced stability and resistance to enzymatic degradation compared to pure synthetic carriers like liposomes, while the engineered components maintain low immunogenicity. The combination of protein capsids with engineered DNA/RNA payloads creates a system that is more stable than non-viral carriers but less immunogenic than traditional viral vectors.
4Object-affected harmful factors
If current non-viral gene delivery systems are used, then immune evasion is possible, but the ability to deliver large genetic payloads or multiple payloads is lost
Solution Approach 1:
The patent segments the delivery system to allow independent optimization of immune evasion and multi-payload capacity. The VLP core can be engineered for low immunogenicity while the separate DNA/RNA components can be designed to carry multiple genetic payloads including large constructs. The segmented architecture allows each component to be optimized for its specific function without compromising the other.
Solution Approach 2:
The patent creates a universal delivery platform that can accommodate multiple types of genetic payloads through the programmable DNA/RNA components. The same VLP structure can deliver different combinations of CRISPR/Cas9 systems, donor DNA templates, and other genetic medicines by simply changing the nucleic acid components, providing multi-functionality without requiring different delivery vehicles for each payload type.
Data Source
AI summary
The invention relates to polymer nanoparticle and DNA nanostructure delivery compositions for non-viral delivery, and methods therefor. More particularly, the invention relates to polymer nanoparticle delivery compositions, such as reversible addition-fragmentation chain transfer (RAFT) polymer compositions, and DNA nanostructure delivery compositions, such as DNA origami compositions, for the delivery of more than one payload, or for the delivery of a nucleic acid construct payload of 3 kB or more, and methods therefor.