mRNA-lipid nanoparticle COVID-19 vaccines: Structure and stability
Linde Schoenmaker1, Dominik Witzigmann2, Jayesh A Kulkarni2
1Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, 2300 RA Leiden, the Netherlands.
International Journal of Pharmaceutics
|April 11, 2021
Summary
mRNA-lipid nanoparticle (LNP) COVID-19 vaccines require cold storage due to instability. Improving mRNA-LNP stability through nucleotide optimization and better understanding of LNP core conditions can ease storage requirements.
Area of Science:
- Biotechnology
- Vaccine Development
- Materials Science
Background:
- Current mRNA-lipid nanoparticle (LNP) vaccines for COVID-19 necessitate stringent ultra-low temperature storage.
- This limits vaccine accessibility and distribution logistics.
Purpose of the Study:
- To review proposed mRNA-LNP structures.
- To identify factors influencing mRNA-LNP stability.
- To discuss strategies for enhancing mRNA-LNP product stability and easing storage conditions.
Main Methods:
- Literature review of proposed mRNA-LNP structures.
- Analysis of factors impacting mRNA integrity within LNPs.
- Discussion of optimization strategies for vaccine stability.
Main Results:
- mRNA hydrolysis is the primary cause of mRNA-LNP instability.
- mRNA, ionizable cationic lipids, and water are core components, while neutral lipids form the outer layer.
- The interaction of water with mRNA in the LNP core and the protective role of lipids remain unclear.
Conclusions:
- Prioritizing mRNA nucleotide composition optimization is crucial for improving vaccine stability.
- Further research into the LNP core environment is needed to enhance mRNA integrity.
- Drying techniques like lyophilization present promising avenues for future exploration.
Keywords:
COVID-19Lipid nanoparticle (LNP)LyophilizationShelf lifeStorage stabilityStructureVaccinemRNAMore Related Videos
Related Concept Videos
RNA Stability
34.5K
Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
34.5K
Conjugated Proteins
23.2K
Simple proteins and protein complexes contain only amino acids. In contrast, many other proteins, called conjugated proteins, covalently bond with non-protein moieties.
Nucleoproteins are protein complexes that contain nucleic acids, categorized as deoxyribonucleoproteins (DNPs) or ribonucleoproteins (RNPs) respectively. The nucleosome is a typical example of a DNP where nuclear DNA is associated with histone proteins. The major antigen for the Covid-19 virus SARS-CoV is an RNP that is critical...
Nucleoproteins are protein complexes that contain nucleic acids, categorized as deoxyribonucleoproteins (DNPs) or ribonucleoproteins (RNPs) respectively. The nucleosome is a typical example of a DNP where nuclear DNA is associated with histone proteins. The major antigen for the Covid-19 virus SARS-CoV is an RNP that is critical...
23.2K
mRNA Stability and Gene Expression
6.0K
The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability
Cis-acting Elements involved in mRNA stability
6.0K
mRNA Stability and Gene Expression
3.1K
3.1K
Viral Structure
69.6K
Viruses are extraordinarily diverse in shape and size, but they all have several structural features in common. All viruses have a core that contains a DNA- or RNA-based genome. The core is surrounded by a protective coat of proteins called the capsid. The capsid is composed of subunits called capsomeres. The capsid and genome-containing core are together known as the nucleocapsid.
69.6K
Nucleic Acid Structure
7.8K
The pentose sugar in DNA is deoxyribose, while in RNA the pentose sugar is ribose. The difference between the sugars is the presence of the hydroxyl group on the ribose's second carbon and a hydrogen on the deoxyribose's second carbon. The phosphate residue attaches to the hydroxyl group of the 5′ carbon of one sugar and the hydroxyl group of the 3′ carbon of the sugar of the next nucleotide, which forms a 5′ to 3′ phosphodiester linkage.
DNA Structure
DNA...
DNA Structure
DNA...
7.8K


