In 2021 there cannot be many people in the world who haven’t heard the term.. mRNA technology powers the first approved Covid-19 vaccines, developed by Pfizer, BioNtech, and Moderna and it has just opened up a whole new world of possibilities for the treatment of diseases, including cancers.
How does mRNA work and what is it?
mRNA medicines are sets of instructions and these instructions direct cells in the body to make proteins to prevent or fight disease. The m stands for messenger and RNA is ribonucleic acid, a part of our DNA. mRNA is a single-stranded molecule that carries genetic code from DNA in a cell’s nucleus to ribosomes, the cell’s protein-making machinery.
Without mRNA, your genetic code would never get used by your body. Proteins would never get made and your body wouldn’t (actually couldn’t) perform its functions. mRNA plays a vital role in human biology, specifically in a process known as protein synthesis. Rather than subjecting you to a long-winded explanation of exactly how mRNA functions, this video provides an excellent overview.
What really matters is what these mechanisms have to do with medicine and how our mastery of nanoparticles has enabled science to manipulate processes at a level hitherto unachievable. The following is an overly simplified explanation to enable you to appreciate the potential of these new medicines. We don’t know how our cellphones work, but we appreciate the benefits they offer.
mRNA, DNA, and your body
Our DNA is ground zero for our bodies. Everything that happens inside us arguably originates in our DNA. It is the machine that powers our bodies and like all machines, is subject to breakages and manufacturing flaws. These can exhibit as diseases later in life, cancer, etc, or conditions that are genetic and affect a person at birth.
mRNA medicines provide us a mechanism to access the actual DNA machinery that regulates our health. Targetted solutions that can repair and address problems right at the source, at ground zero.
mRNA medicines depend on really small nanoparticles to deliver the medicine’s payload or instructions. Solid lipid nanoparticles provide transport and measure anywhere from 1 to 1000 nanometres. To give you an idea of their scale, imagine this.
In the International System of Units, the prefix “nano” means one-billionth; so one nanometer is one-billionth of a meter. It’s difficult to imagine just how small that is, so here are some examples:
- A sheet of paper is about 100,000 nanometers thick.
- A strand of hair is 80,000 –100,000 nanometers in diameter.
- There are 25,400,000 nanometers per inch.
- Your fingernails grow about one nanometer per second!
It turns out these solid lipid nanoparticles (SLNP’s) are hugely important to the development of mRNA medicines and we’ve been tinkering with them since the early ’90s. The body easily accepts them without risk of rejection as companies now focus on the use of physiological lipids. They offer the perfect carrier.
The first drug using SLNP’s as a delivery mechanism, Onpattro was approved in 2018. You can read more about their delivery system for this drug here and as we all now know, in late 2020, several life-saving mRNA vaccines for SARS-CoV-2 were released. Moderna’s mRNA-1273 and Pfizer/BioNTech’s BNT162b2, also use lipid nanoparticles for their drug delivery system.
mRNA medicines have finally truly “arrived”. Their development over nearly three decades is a testament to open scientific collaboration, innovation, and sheer perseverance. The question now is what else can we use this novel technology for, and how can we use it to address disease?
Looking to tomorrow
Imagine the potential for being able to address diseases and genetic “glitches” at their root. Unborn children with identified genetic abnormalities could be born as healthy infants, thanks to early interventions made possible with these medicines.
Cancers and other diseases are currently being explored, to see how we can apply these drugs. High on the list are autoimmune disorders, a natural starting point after the success of the vaccine, and the technology’s established ability to impact the immune system. Recently, a team led by Ugur Sahin has designed an mRNA vaccine that can restore tolerance to myelin proteins in mice, reducing the severity of multiple sclerosis-like symptoms, while maintaining the immune response towards other antigens.
On the subject of mRNA Cancer Vaccines, a recent article in PubMed suggests another novel application for mRNA. Apart from being used directly to vaccinate patients, mRNAs can also be used in cellular therapies to transfect patient-derived cells in vitro and infuse the manipulated cells back into the patient. The technology is so rapid and cost-effective that it can be tailored to individual patients and their particular genetic code.
mRNA may be on course to do for modern medicine what Flemming’s penicillin did for healthcare in the early twentieth century. It holds out huge promise that may, for now, only be limited by existing technology and our ability to innovate. Watch this space.
