Nano-structural Protein Degradation Tool for Blood-Brain Barrier Penetration
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Solution Overview
Problem
Current targeted protein degradation tools face challenges such as complex design, laborious synthesis methods, poor structural flexibility, and limited biological barriers penetrating capacity, making them inefficient for targeting extracellular and membrane proteins, particularly across biological barriers like the blood-brain barrier.
Innovation Solution
Development of nano-structural protein degradation tools that link protein-of-interest recognition groups to linkers or nanoparticles, forming multi-layer structures with antibodies, peptides, or nucleic acid aptamers, enabling targeted protein degradation without relying on specific receptor-ligand matching pairs and allowing for tissue-specific targeting.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional TPD tools (PROTAC, LYTAC) are used, then targeted protein degradation can be achieved, but the design and synthesis process becomes complex and laborious requiring case-by-case design for different diseases and cell types
Solution Approach 1:
The patent creates a universal TPD platform where a single nanoparticle core can be combined with different POI recognition groups (antibodies, peptides, aptamers) and linkers to target multiple different proteins and cell types. This eliminates the need for case-by-case de novo synthesis, as the same nanoparticle platform can be adapted to different applications by simply changing the recognition group and linker components.
Solution Approach 2:
The TPD tool is divided into separate functional modules: a nanoparticle core, linkers, and POI recognition groups. Each module can be independently designed, synthesized, and optimized. The recognition groups can be selected from existing libraries rather than synthesized de novo for each application, significantly reducing the laborious design and synthesis process.
2Ease of operation
If LYTAC with receptor-ligand matching pairs is used, then protein complex can be hijacked into cells, but the structure needs to be specially designed and modified for different cell targeting making it tedious and difficult
Solution Approach 1:
The nanoparticle core serves as a universal platform that can be combined with various POI recognition groups to target different cell types and proteins. The same nanoparticle can be used for different applications by simply changing the recognition group, providing both ease of operation and high adaptability without requiring structural modifications for each cell type.
Solution Approach 2:
The patent introduces linkers as intermediary components that connect the nanoparticle core to the POI recognition groups. These linkers act as flexible mediators that can accommodate different recognition groups and target configurations, enabling easy adaptation to different cell types and proteins without modifying the core nanoparticle structure.
3Reliability
If existing TPD tools are designed for intracellular proteins, then degradation mechanism can be established, but extracellular proteins and membrane proteins (40% of total proteins) remain inaccessible
Solution Approach 1:
The nanoparticle-based TPD platform is designed to be universally applicable to all protein locations including intracellular, extracellular, and membrane proteins. By combining the nanoparticle with appropriate POI recognition groups, the system can target and degrade proteins regardless of their cellular location, expanding coverage to include the previously inaccessible 40% of proteins.
Solution Approach 2:
The patent transitions from conventional intracellular-focused TPD to a multi-dimensional approach that can access proteins in different cellular compartments and locations. The nanoparticle platform enables degradation to occur in extracellular space and at membrane surfaces, adding new spatial dimensions to protein degradation capability.
4Reliability
If conventional TPD tools are used, then protein degradation can be achieved in accessible tissues, but biological barriers like blood-brain barrier prevent targeting of inaccessible tissues
Solution Approach 1:
The nanoparticle platform provides a universal system that can be adapted to cross various biological barriers including the blood-brain barrier. By selecting appropriate POI recognition groups and linkers, the same nanoparticle core can target proteins in accessible tissues as well as in protected compartments like the brain, expanding versatility to include previously inaccessible tissues.
Data Source
AI summary
The present disclosure provides a nano-structural protein degradation tool, use, and a preparation method thereof, wherein the nano-structural protein degradation tool comprises: one of or a combination of several of a first degradation tool, a second degradation tool, and a third degradation tool, wherein the first degradation tool is formed by linking POI recognition groups to linkers; the second degradation tool is formed by linking the POI recognition groups to nanoparticles; and the third degradation tool is formed by linking the POI recognition groups to the nanoparticles through the linkers. The present disclosure further provides a lipid-based protein degradation tool, use, and a preparation method thereof, wherein the lipid-based protein degradation tool comprises: POI recognition groups, and lipid hybrid substances linked to the POI recognition groups.