Biodegradable Amino-Ester Nanoparticles for mRNA Delivery
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Solution Overview
Problem
Current methods for delivering CRISPR/Cas9 mRNA face challenges due to its large size and negative charge, leading to inefficient delivery and potential off-target effects, and existing lipid-like nanoparticles are not biodegradable, causing side effects.
Innovation Solution
Development of amino ester compounds and lipid-like nanoparticles comprising these compounds, non-cationic lipids, polyethylene glycol-lipids, and sterols for efficient and biodegradable delivery of mRNA, including CRISPR/Cas9 mRNA, to improve therapeutic and diagnostic applications.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing lipid-like nanoparticles are used for mRNA delivery, then delivery efficiency is improved, but biodegradability is poor causing side effects
Solution Approach 1:
The patent modifies the chemical structure of lipid-like nanoparticles by incorporating biodegradable ester bonds and adjustable chain lengths in the lipid tail (varying m values), which changes the degradation parameters while maintaining delivery efficiency. This allows the nanoparticles to break down into harmless components after delivering mRNA, eliminating the side effects associated with non-biodegradable lipids.
Solution Approach 2:
The invention creates composite lipid-like nanoparticles combining multiple components including biodegradable ester-linked lipids, cholesterol, and PEGylated lipids. This composite structure achieves both efficient mRNA delivery and controlled biodegradation, resolving the contradiction between delivery performance and safety.
2Reliability
If CRISPR/Cas9 mRNA is delivered using conventional methods, then some delivery is achieved, but delivery efficiency is low due to large size and negative charge
Solution Approach 1:
The patent uses lipid-like nanoparticles as intermediary carriers that interact with the negatively charged CRISPR/Cas9 mRNA through electrostatic interactions. These nanoparticles shield the mRNA's negative charge and large size, enabling efficient cellular uptake while maintaining the integrity and specificity of the mRNA, thereby reducing off-target effects.
3Object-generated harmful factors
If biodegradable bonds are introduced to improve elimination, then tolerability is improved, but delivery efficiency may be reduced
Solution Approach 1:
The patent introduces dynamic ester bonds that remain stable during circulation and mRNA delivery but become hydrolyzable under specific cellular conditions (such as lysosomal environment). This dynamic property allows the nanoparticles to maintain structural integrity for efficient delivery while automatically degrading into harmless products after completing their function, thus achieving both high delivery efficiency and excellent tolerability.
Data Source
AI summary
The present disclosure relates to a series of biodegradable amino-ester lipid-like nanoparticles. In some embodiments, the biodegradable amino-ester lipid-like nanoparticles are used in methods for the delivery of nucleic acids.