Poly(beta-amino ester) mRNA Carrier Tissue Targeting
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Solution Overview
Problem
Existing mRNA delivery systems face challenges in achieving efficient, specific, and multi-tissue targeted delivery due to their complexity, toxicity, and limited ability to target extrahepatic tissues.
Innovation Solution
A tissue-selective single-component mRNA delivery system utilizing poly(β-amino ester) polymers as the sole delivery carrier, which allows for localized regulation of chemical structures and microregion charge to achieve targeted enrichment in various tissues, including lung, liver, and spleen.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If multiple-component lipid nanoparticles are used for mRNA delivery, then delivery efficiency and protection are improved, but system complexity and formulation difficulty increase
Solution Approach 1:
The patent merges multiple lipid nanoparticle components (cationic lipid, PEG lipid, cholesterol, phospholipid) into a single poly(β-amino ester) polymer component that performs all necessary functions: mRNA loading, protection, stability maintenance, and lysosomal escape assistance
Solution Approach 2:
The poly(β-amino ester) polymer is designed with multi-functional capabilities including mRNA binding, cellular uptake promotion, endosomal escape facilitation, and stability maintenance, replacing the need for multiple specialized components
2Reliability
If PEG-containing lipid nanoparticles are used, then mRNA protection and delivery are improved, but allergic reactions and rapid clearance increase
Solution Approach 1:
The patent removes PEG-containing components from the delivery system entirely, replacing them with poly(β-amino ester) polymers that provide equivalent protection without the harmful allergic reactions and rapid clearance associated with PEG
Solution Approach 2:
The patent converts the potentially harmful PEG components into beneficial poly(β-amino ester) polymers that maintain mRNA protection and delivery efficacy while eliminating allergic reactions and rapid clearance issues
3Productivity
If conventional lipid nanoparticles are used, then mRNA delivery is achieved, but liver enrichment occurs and extrahepatic tissue targeting is difficult
Solution Approach 1:
The patent modifies the poly(β-amino ester) polymer structure with specific functional groups and charge characteristics that enable selective accumulation in extrahepatic tissues such as lung, spleen, and liver, achieving local quality enhancement for tissue-specific targeting
Solution Approach 2:
The patent changes the chemical parameters of the delivery carrier by using poly(β-amino ester) polymers with adjustable molecular weight, charge density, and structural features to optimize tissue distribution and achieve targeted delivery to specific extrahepatic organs
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 system enables efficient and selective targeting of multiple tissues with a single component carrier, reducing the complexity of drug formulation and minimizing side effects, thereby facilitating the treatment of multiple diseases across different tissues.
Implementation Method 1
The delivery carrier comprises a cationic or ionizable lipid, polyethylene glycol (PEG) lipid molecules, structural lipid molecules cholesterol, and auxiliary phospholipid molecules
Implementation Method 2
assisting in the escape from lysosomes/endosomes
Data Source
AI summary
The present application is related to a tissue-selective single-component mRNA delivery carrier and a delivery system. Poly (β-amino ester) polymer is used as the single-component delivery carrier, wherein the poly (β-amino ester) polymer has a structure as shown in Formula I or Formula II. In Formula I or Formula II, the definition of each substituents is the same as in the detailed description. The present invention employs only the poly(β-amino ester) polymer material as the single delivery carrier, and tissue-selective targeting of the delivery system including lung, liver and spleen, etc. can be achieved by locally regulating the chemical structures and the domain charges of the poly(β-amino ester) polymer.