Abstract
Nanoparticles are tiny containers that scientists create to carry molecules. How tiny? Let us say that a nanoparticle is about 100,000 times smaller than a single M&M candy. Scientists use special nanoparticles to treat specific diseases. For example, the mRNA vaccines that protect people from COVID-19 contain nanoparticles that are packed with mRNA molecules from the virus. In this article, we will answer some interesting questions: What are nanoparticles made of and how do they work? What are the mRNA molecules that are packed inside the nanoparticles of the COVID-19 vaccine? How do scientists create mRNA vaccines, and how do they protect us from COVID-19?
How Vaccines Work
All vaccines work in a similar way. The idea behind any vaccine is to introduce into the body weakened viruses or bacteria (or even just a piece of a disease-causing virus or bacteria), that will be harmless but will still stimulate the body’s immune system. This way, the body can “practice” on a harmless form of the disease-causing organism and become prepared to protect us when the actual, dangerous form of the virus or bacteria arrives. The immune system is very accurate and has a type of memory. For example, if you are vaccinated against a virus, your immune system generally recognizes and protects you against that virus for a long time after vaccination. Mostly, the immune system recognizes proteins on the surface of a bacterium or virus. For the rest of this article, we will focus specifically on viruses, although much of what we will tell you also applies to bacteria.
The immune response is complicated and includes several types of cells, including T cells that can bind to and destroy cells that are infected by viruses, and B cells that can produce proteins called antibodies
The first vaccines that were created gave people’s immune systems a chance to react against viral proteins by introducing whole weakened or dead viruses into their bodies. But technology has advanced, so today’s scientists can create vaccines based on the exact proteins they want the immune system to react to, without introducing the entire virus into the body. While there are several methods to do this, we will focus on how scientists use mRNA lipid nanoparticle (mRNA-LNP) vaccines
From DNA to Protein
Both RNA and DNA are molecules called nucleic acids
Nucleic acids are made of chains of molecules called nucleotides
After scientists discovered the genetic code, they could create the instructions for any protein, by making the mRNA molecules that code for that protein. In the case of mRNA-LNP vaccines, the mRNA codes for a surface protein of a virus—the structure on which scientists want the immune system to practice. The challenge with mRNA molecules, however, is that they are fragile and difficult to get inside of cells. For this reason, scientists invented the second component of the mRNA-LNP vaccines—the lipid nanoparticles, which both protect mRNA molecules and transport them into cells.
What Are Lipid Nanoparticles?
Nanoparticles

- Figure 1 - The nanoscale includes the range between 1 and 100 nanometers.
- Lipid nanoparticles are about 100,000 times smaller than an M&M candy.

- Figure 2 - Lipid nanoparticles (LNPs) are made of nucleic acids (mRNA) and lipids that are rapidly mixed.
- Ionizable lipids have a positive charge, while mRNA molecules (and other nucleic acids) have a negative charge, therefore they stick together to create tiny clumps of mRNA molecules surrounded by ionizable lipids. Other lipids, named structural lipids, also participate in creating these clumps and are responsible for creating an outer layer surrounding the mRNA clumps, forming the LNPs. An electron microscope can be used to see the structures of mRNA-LNPs and measure their size.
Lipid nanoparticles
The main component in LNPs is a type of lipid called an ionizable lipid
RNA Molecules as Medicines
Combining mRNA and LNPs in this way, scientists can now efficiently create any protein they want inside cells. LNPs can also be used to transport other types of nucleic acid molecules. For example, the first LNP drug, approved in 2018, delivered interfering RNA (RNAi) molecules that as opposed to mRNA, prevent the formation of proteins in the liver cells of patients who suffer from a liver disease called amyloidosis. Recently, two mRNA-LNP vaccines have been approved to protect the population from COVID-19. These vaccines use LNPs to deliver mRNA molecules coding for a specific protein found on the surface of the COVID-19 virus, called the spike protein
How Does the mRNA Vaccine Against COVID-19 Work?
mRNA-LNP vaccines are injected into the muscle, where they are swallowed by muscle and immune cells. After entering the cells, the mRNA-LNPs release their mRNA molecules into the cells’ cytoplasm. In the cytoplasm, ribosomes “read” the code on the mRNA, using it to create the viral spike protein.
When the spike protein breaks down inside cells, small pieces of it are moved to the cell membrane, where they are “shown” to T cells and B cells. These immune cells recognize the spike protein as foreign (not from a human) and create an immune response, including antibodies against it. Eventually, the mRNA from the vaccine breaks down and all that remains is the immune system’s memory (Figure 3) [4].

- Figure 3 - The immune response to mRNA-LNP vaccines.
- mRNA-LNPs are swallowed by muscle or immune cells. The genetic code in the mRNA is translated by the ribosome to create the spike protein. When the spike protein breaks down, pieces of it travel to the cell membrane where they can trigger the T and B cells of the immune system, “training” them to fight against the COVID-19 virus.
Why Are mRNA-LNP Vaccines a Breakthrough?
mRNA-LNP vaccines are relatively safe, very effective, and can be produced quickly. Scientists can simply make any desired mRNA that codes for a specific protein, and pack it within the LNPs. That makes LNPs a very useful tool. Also, since the mRNA molecules are destroyed in the cytoplasm, do not enter the nucleus, and do not affect the DNA, these vaccines are safe. This type of vaccine is the result of many years of research invested by great scientists who were very helpful in the fight against the COVID-19 pandemic.
Glossary
Antibodies: ↑ Proteins produced by B cells of the immune system to fight invading viruses and bacteria.
mRNA Lipid Nanoparticle (mRNA-LNP) Vaccines: ↑ Vaccines made of lipid nanoparticles containing mRNA that codes for a viral protein.
Nucleic Acids: ↑ Molecules made out of units called nucleotides, come in two naturally occurring varieties: deoxyribonucleic acid (DNA) and ribonucleic acid (RNA).
Ribosome: ↑ A cellular “factory” that makes proteins.
Messenger RNA (mRNA): ↑ An RNA molecule that carries a gene’s code from the DNA in the nucleus to the ribosome in the cytoplasm, to produce a protein.
Nucleotides: ↑ Building blocks that form nucleic acids.
Amino Acids: ↑ Building blocks that form a protein.
Nanoparticles: ↑ Small particles that range from 1 to 100 nm in size; a nm is one-millionth of a mm.
Lipid Nanoparticles: ↑ Nanoparticles made of lipids and nucleic acids.
Ionizable Lipid: ↑ A class of lipid molecules that has the ability to gain a positive charge or remain neutral.
Spike Protein: ↑ Protein that expresses on the surface of SARS-COV2 viruses and allows them to penetrate host cells.
Conflict of Interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
References
[1] ↑ Tregoning, J. S., Flight, K. E., Higham, S. L., Wang, Z., and Pierce, B. F. 2021. Progress of the COVID-19 vaccine effort: Viruses, vaccines and variants vs. efficacy, effectiveness and escape. Nat. Rev. Immunol. 21:626–36. doi: 10.1038/s41577-021-00592-1
[2] ↑ Kon, E., Elia, U., and Peer, D. 2022. Principles for designing an optimal mRNA lipid nanoparticle vaccine. Curr. Opin. Biotechnol. 73:329–36. doi: 10.1016/J.COPBIO.2021.09.016
[3] ↑ Dammes, N., and Peer, D. 2020. Paving the road for RNA therapeutics. Trends Pharmacol. Sci. 41:755–75. doi: 10.1016/j.tips.2020.08.004
[4] ↑ Alameh, M. G., Tombácz, I., Bettini, E., Lederer, K., Sittplangkoon, C., Wilmore, J. R., et al. 2021. Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses. Immunity 54:2877–92.e7. doi: 10.1016/J.IMMUNI.2021.11.001