RNA Nanoparticles Self-Assembly for Targeted Delivery
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Solution Overview
Problem
Current methods for delivering therapeutic and diagnostic agents face challenges such as poor targeting specificity, immune response, and stability issues with RNA nanoparticles, limiting their effectiveness in treating diseases.
Innovation Solution
Design and synthesis of polyvalent RNA nanoparticles that self-assemble into predefined three-dimensional shapes, allowing for the encapsulation and controlled release of therapeutic molecules, with optimized 3′-tail connectors for spatial addressability and reduced immune response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If RNA molecules are used to construct nanoarchitectures, then complex tertiary structures and novel RNA-RNA interaction motifs are provided, but chemical lability increases compared to DNA
Solution Approach 1:
The patent employs modified nucleosides (2'-O-methyl, pseudouridine, 5-methylcytidine) to change the chemical parameters of RNA, enhancing stability while preserving the ability to form complex tertiary structures and functional motifs
Solution Approach 2:
The patent creates composite RNA-DNA hybrid structures and RNA-protein complexes, combining the structural versatility of RNA with the stability of DNA or protective proteins, thereby achieving both complex architecture and chemical reliability
2Measurement precision
If RNA nanoparticles are designed for targeted delivery, then specific cell recognition and therapeutic treatment are enabled, but immune response may increase
Solution Approach 1:
The patent functionalizes specific local regions of the RNA nanoparticle surface with targeting ligands (aptamers, peptides, antibodies) while keeping the core structure immunomodulatory, achieving targeted delivery without uniform immune activation across the entire particle
Solution Approach 2:
The patent utilizes the immune-stimulating capacity of RNA to activate immune cells (dendritic cells, macrophages) for therapeutic benefit in cancer treatment, converting potential harmful immune response into beneficial immune activation through controlled delivery to target cells
3Shape
If DNA structures are constructed using single stranded DNA, then various polyhedral shapes are achieved, but assembly yields are poor due to unspecific assembly
Solution Approach 1:
The patent divides the assembly process into hierarchical stages: first forming stable secondary structure motifs (hairpins, junctions), then assembling these into tertiary structures, and finally organizing into quaternary polyhedral assemblies, with each stage providing specificity for the next
Solution Approach 2:
The patent pre-folds RNA molecules into defined secondary structures (stem-loops, junctions) with specific geometric arrangements before assembly, ensuring that the building blocks are pre-configured for high-fidelity assembly into target polyhedral shapes, eliminating unspecific assembly
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
The RNA nanoparticles achieve targeted delivery with reduced immune response and improved stability, enabling efficient therapeutic and diagnostic functions, particularly in cancer treatment.
Implementation Method 1
The RNA motifs allow for non-covalent assembly between 2 or more building blocks
Implementation Method 2
a motif that allows for non-covalent assembly between 2 or more building blocks
Data Source
AI summary
The instant invention provides polyvalent RNA nanoparticles comprising RNA motifs as building blocks that can form RNA nanotubes. The polyvalent RNA nanoparticles are suitable for therapeutic or diagnostic use in a number of diseases or disorders.