Lipid Nanoparticles with Low PEG Lipid for mRNA Delivery
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Solution Overview
Problem
Current lipid-based nanoparticles for mRNA delivery face challenges with instability and low cell penetrating potential, particularly due to high levels of PEG lipids and imbalanced ionizable lipid to phospholipid ratios, which hinder effective immunogenic delivery.
Innovation Solution
The development of lipid nanoparticles comprising less than 1 mol % C14-PEG2000 lipid, with a high ratio of ionizable lipid to phospholipid (6:1-11:1) and moderate to high levels of sterol, optimized to facilitate immunogenic delivery of mRNA by enhancing stability and cell uptake.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If high levels of PEG lipids (at least 1.5 mol %) are used in lipid nanoparticles, then the nanoparticles show improved stability and reduced immunogenicity, but cell penetrating potential and immunogenic delivery capability are reduced
Solution Approach 1:
The patent applies parameter changes by reducing the PEG lipid concentration from the conventional at least 1.5 mol % to less than 1 mol %. This parameter modification resolves the contradiction by improving cell penetrating potential and immunogenic delivery capability while maintaining adequate nanoparticle stability through optimized ionizable lipid and phospholipid ratios.
2Productivity
If high ratio of ionizable lipid to phospholipid (6:1-11:1) is used, then immunogenic delivery capability is improved, but nanoparticle stability may be compromised
Solution Approach 1:
The patent applies parameter changes by optimizing the ionizable lipid to phospholipid ratio to a specific range of 6:1 to 11:1, with ionizable lipid at 50-70 mol % and phospholipid at less than 10 mol %. This optimized ratio balance resolves the contradiction by achieving high immunogenic delivery capability while maintaining nanoparticle stability through the specific compositional parameters.
Solution Approach 2:
The patent applies composite materials by creating a multi-component lipid system comprising ionizable lipid, phospholipid, sterol, and PEG lipid in specific ratios. The synergistic interaction between these different lipid components resolves the contradiction by providing both the high immunogenic delivery capability (from the ionizable lipid dominant composition) and the necessary stability (from the balanced composite structure).
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 C14-PEG2000 lipid; as well as particular percentages of the other lipids. 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.