In-vivo and Ex-vivo Delivery Systems
Our cells are prolific protein factories.
Harnessing the potential of mRNA - The next wave of scientific innovations in the fight against pathogens
How Do Viruses Make Us Sick?
Our cells are prolific protein factories.
Turning your body into medicine factories
Messenger RNA is a molecule that contains the instructions which turn our cells into protein-making factories using their natural machinery.1 How can this technology be used to treat or prevent diseases? The answer comes down to two basic biological principles:
Our cells are super protein factories – our cells produce tens of thousands of different proteins that perform all the work in our bodies1— from the enzymes that help us digest food, to the fibres which make our muscles move. Messenger RNA is a crucial component of this protein-building process, acting as a single-page recipe which is read and used by our cells to create these life-sustaining biomolecules.
Proteins can also be medicine – proteins can help defend our body against pathogens, but they can also be reintroduced to our cells to restore correct function of our organs and tissues.1 Depending on the condition, the malleability of mRNA allows for its instructions to be tailored and adapted for the production of a specific therapeutic protein. These proteins, for example, may be beneficial in helping to fight cancer2 or teaching the immune system to recognise a particular virus.
Swift and nimble
Whereas some vaccines may use inactivated or weakened forms of a pathogen to teach the body to protect itself3, the mRNA platform does so by teaching our cells to build the target proteins found on the intruder’s surface. This makes mRNA technology extremely nimble, allowing scientists to obtain new molecule-building instructions and ‘plugging’ them into the mRNA vaccine for testing and development with speed which is not permissible with conventional vaccine approaches. These particles trigger an immune response, springing our antibodies and T-cells to action, all while training the immune system for potential future attacks. This prepares our body for when the real infectious organism comes along, and if it does, it will sound the alarm to help defend against infection and illness.
Another key trait of mRNA is that it is very short-lived. Shortly after your cellular machinery uses it to make a protein, it’s destroyed. It doesn’t linger in the body. And because it doesn’t enter the cell’s nucleus, it can’t interact with your DNA.
mRNA instructions can be adapted against a specific pathogen and delivered to our cells to build protein.
Inside the delivery vehicles critical to the success of mRNA
As a notoriously fragile molecule, mRNA requires specialised carriers to allow for its safe and secure delivery. These 'trucks', known as lipid nanoparticles or LNPs, and are tiny protective bubbles of fat which shuttle these mRNA molecules into our cells.
As Pfizer expands its mRNA programmes into new vaccines and therapies, LNPs will continue to be critical to the success of these potential medical advances. In addition, the development of mRNA and LNP technology for new therapeutic areas will benefit from other innovations, including how LNPs are formulated and manufactured.
The challenge which scientists face now is modifying these delivery vehicles to be able to reach new cell types and carry different types of cargo. To treat rare genetic diseases, for example, the LNPs will need to reach a particular tissue or organ in the body, such as the liver, kidneys, or heart.
What's next for mRNA?
While mRNA has become a key topic of conversation in recent years, it’s certainly not new. Scientists have been working on mRNA medicines and vaccines for decades, and it is this foundation of research which is now allowing further development in the application of mRNA to other areas of healthcare.
Messenger RNA can play a key role in the fight against viruses susceptible to mutation. The common flu for instance poses a challenge for traditional flu vaccines. It requires scientists to work months in advance to predict which influenza strains will be dominant in the upcoming season, and depending on how well the flu shot matches the prevalent strain, its effectiveness can vary year to year. Here the flexibility of mRNA could offer a significant advantage by allowing scientists to quickly “edit” vaccines to better match against the currently circulating variants.
Our cells display the surface protein like a “wanted poster”—teaching the immune system to recognize and protect against the pathogen.
Currently mRNA vaccines are also being investigated for the potential prevention of shingles - a painful infection caused by the same virus as chicken pox. Nearly one in three adults will experience shingles at least once in their lifetime, with episodes lasting from three to five weeks.
Looking beyond vaccines, mRNA technology may also help patients with rare diseases. Ongoing research indicates that mRNA could be used as a new approach to gene editing by delivering “tools” that have the potential to add, remove, or correct faulty genes in patients. These tools rely on the guidance of RNA which specifies the exact location of the malfunctioning genetic material, consequently allowing the tool to cut at the precise point where the mutation occurs and add, correct, or completely remove the target piece of the genome. This next-generation technology could be transformative in repairing single-gene mutations such as haemophilia or cystic fibrosis.
The success of mRNA vaccines has opened the floodgates for scientific innovation across a vast range of diseases and offers new hope for patients with limited treatment options. As we enter this new era of mRNA medicine, our scientists, engineers, and talent around the globe will continue to apply their experience, agility, and focus to deliver breakthrough treatments to improve patients’ lives.