Lipid Nanoparticles With Low PEG Lipid for mRNA Delivery
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Solution Overview
Problem
Current lipid-based nanoparticle compositions for mRNA delivery often face challenges with instability and low cell penetrating potential, particularly due to high levels of PEG lipids which can hinder immunogenic delivery.
Innovation Solution
Lipid nanoparticles comprising less than 1 mol % of PEG lipid, specifically using diC18-PEG2000 lipid, are formulated to enhance immunogenic delivery of mRNA by optimizing the composition with ionizable, phospholipid, sterol, and PEG lipid ratios for improved stability and cell uptake.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If high levels of PEG lipids (at least 1.5 mol %) are used in LNP composition, then nanoparticle stability is improved, but immunogenic delivery capability deteriorates
Solution Approach 1:
The patent applies parameter changes by precisely controlling the PEG lipid concentration to be less than 1 mol % (specifically 0.1-0.9 mol %), which is a significant reduction from conventional levels of at least 1.5 mol %. This parameter optimization resolves the contradiction by finding a concentration range that maintains adequate nanoparticle stability while eliminating the harmful immunogenic suppression effect caused by excessive PEG lipids.
2Object-generated harmful factors
If PEG lipid concentration is reduced to less than 1 mol %, then immunogenic delivery is enhanced, but nanoparticle stability may deteriorate
Solution Approach 1:
The patent resolves this contradiction by identifying an optimal parameter range for PEG lipid concentration (0.1-0.9 mol %) that is sufficiently low to enhance immunogenic delivery capability while remaining high enough to maintain basic nanoparticle stability. This precise parameter optimization demonstrates that extreme reduction below 1 mol % can simultaneously achieve both goals.
3Ease of operation
If diC14 based PEG lipids (DMG-PEG) are used, then conventional delivery is achieved, but immunogenic response is suppressed
Solution Approach 1:
The patent applies local quality by specifically selecting diC18-PEG lipid structure (with C18 fatty acid chains) instead of conventional diC14-PEG lipids (DMG-PEG). This structural modification at the molecular level changes the local properties of the PEG component, allowing the nanoparticle to maintain delivery efficiency while simultaneously enabling immunogenic response, thereby resolving the contradiction between delivery efficiency and immunogenic suppression.
4Ease of operation
If conventional LNP composition with at least 1.5 mol % PEG lipid is used, then non-immunogenic delivery is achieved, but vaccine efficacy deteriorates
Solution Approach 1:
The patent resolves this contradiction by changing the PEG lipid concentration parameter to less than 1 mol % (specifically 0.1-0.9 mol %), which transforms the LNP from non-immunogenic delivery vehicles into effective vaccine platforms. This parameter change maintains sufficient delivery function while enabling robust immunogenic response, thereby achieving both delivery efficiency and vaccine efficacy simultaneously.
Data Source
AI summary
The present invention relates to the field of lipid nanoparticles (LNP); more specifically comprising an ionizable lipid, a phospholipid, a sterol, a PEG lipid and one or more nucleic acids. The LNP's of the present invention are characterized in comprising less than about 1 mol % of a C18-PEG2000 lipid. The present invention provides use of the LNP's for immunogenic delivery of nucleic acid molecules, specifically mRNA; thereby making them highly suitable for use in vaccines, such as for the treatment of cancer or infectious diseases. Finally, methods are provided for preparing such LNP's.