Immunogenic LNP Compositions for Room-Temperature RNA Storage
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Solution Overview
Problem
RNA-based vaccines face challenges such as instability due to ribonuclease degradation and difficulty in crossing cell membranes, requiring subzero storage that affects colloidal stability and RNA exposure, and traditional vaccines provide limited protection against influenza strains and have long production times.
Innovation Solution
A composition comprising a first lipid nanoparticle encapsulating RNA with a cryoprotectant and optionally a second lipid nanoparticle, maintaining effective concentration and stability through the use of saccharides like sucrose, allowing storage at room temperature and enhancing RNA encapsulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If subzero storage is used to maintain RNA stability in LNP formulations, then RNA integrity is improved, but colloidal stability of LNPs deteriorates and RNA exposure increases
Solution Approach 1:
The patent changes the storage temperature parameter from subzero to room temperature by formulating the LNP composition with specific lipid ratios and incorporating cyclodextrin complexes. This parameter change enables RNA stability to be maintained without requiring freezing, thereby preserving colloidal stability and preventing RNA exposure while ensuring RNA integrity through the modified formulation composition rather than low temperature storage.
2Productivity
If traditional influenza vaccines are used, then production time is reduced, but protection breadth against influenza strains is limited
Solution Approach 1:
The patent changes the approach from traditional inactivated influenza vaccines to mRNA-based vaccines delivered via LNP. This fundamental parameter change enables rapid production by directly encoding influenza antigens in mRNA form, eliminating the need for virus cultivation and inactivation processes. The LNP formulation allows for quick adaptation to different influenza strains by simply changing the mRNA sequence, thereby achieving both rapid production and broad protection across multiple influenza subtypes.
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 composition maintains RNA integrity and stability for extended periods at various temperatures, increasing encapsulation efficiency and reducing colloidal instability, enabling rapid vaccine development and broad protection against influenza strains.
Implementation Method 1
The composition comprises a cryoprotectant, wherein the first lipid nanoparticle encapsulates a ribonucleic acid (RNA) polynucleotide... the effective concentration of the first lipid nanoparticles is a function of availability of the water molecules in the vicinity of their microenvironment
Implementation Method 2
RNA delivery formulations (such as lipid nanoparticles (LNPs)) have been used to help stabilize and protect RNA molecules from degradation by ribonucleases
Implementation Method 3
the first lipid nanoparticle encapsulates a ribonucleic acid (RNA) polynucleotide having an open reading frame encoding at least one antigen... maintaining the long-term stability of RNA in the LNP formulations
Implementation Method 4
enhance efficient cellular uptake and intracellular delivery of the RNA payload
Implementation Method 5
RNA alone does not readily cross a cell membrane to enter target cells upon injection
Data Source
AI summary
The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of ribonucleic acid immunogenic compositions and/or vaccines comprising polynucleotide molecules preferably encoding one or more influenza antigens, such as hemagglutinin antigens, wherein the composition is frozen or lyophilized.