How Can BioPlatforms Support the mRNA “Revolution”

The science and medicine worlds are experiencing a new revolution, and this time the protagonist is the mRNA molecule. In this article, we explore why bioplatforms support this revolution.

How did mRNA arrive to the medicine world?

mRNA molecules have the power to direct a cell’s function. mRNA is a code that, when read by a cell’s machinery, creates a functional protein. Today, the potential use of mRNA in medicine is well recognized, but — as happens with many innovative scientific discoveries — that wasn’t always the case. Dr. Katalin Karikó built her scientific career studying mRNA with the purpose of using it to treat human diseases. Since the 1970s, Dr. Karikó perceived mRNA’s potential. But only after four decades of her struggling to get grants for research and laboratories to work in were her ideas widely recognized. In 2020, when the COVID-19 pandemic hit, the first mRNA-based vaccine was authorized for human use.  

The mRNA revolution is not only based on the success of mRNA vaccines for COVID-19, but also the development of innovative cancer therapies using mRNA-based vaccines.

“Because of the COVID-19 vaccine success, mRNA is getting a lot of attention, but if we look at the history of mRNA technology, it started with cancer vaccine development,” says Dr. Jinjun Shi, associate professor at the Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School. “Most of the design work that was being conducted for mRNA cancer vaccines was then applied to COVID-19 vaccines.”

The development of mRNA-based vaccines or therapies relies on bioplatforms. One of the reasons COVID-19 vaccines were developed in a very short time is because bioplatforms for other infectious diseases — or cancer vaccines — were already established. 

What is a bioplatform, and how it’s used in mRNA medicine?

Bioplatforms involve special organizational and technological structures that biotech companies build to make their resources and technology reusable — and even cross-therapeutic. Ultimately, by making minor changes to a bioplatform in the drug discovery pathway, the development of new therapies for very different diseases can be achieved in a short time.

Take COVID-19 mRNA-based vaccines as an example. These vaccines deliver mRNA encoding the viral spike protein. By 2020, when the SARS-CoV-2 genomic sequence was known, some biotech companies working on mRNA vaccines for other diseases already had a bioplatform built. They were able to efficiently switch the specific spike protein mRNA sequence to use on their formulation. The rest of the drug discovery pathway was already implemented, like the mRNA manufacturing protocol, the cargo molecules to use, the delivery method and more.

Bioplatforms also provide a fast adaptation to changes. If the virus undergoes mutation — modifying its spike protein in a certain way such that the commercialized vaccines no longer prevent the disease — the bioplatform permits the development of a different vaccine against the new variant. A change to the mRNA to encode the new mutated sequence is all that is required. In this case, the vaccine development could be even faster, since clinical trials performed in humans to prevent COVID-19 infection already demonstrated vaccine safety, tolerability and efficacy, and explored important properties such as mRNA concentration, number of doses and delivery methods. This method is applicable to many viruses, not just SARS-CoV-2.

Bioplatforms for finding a cure for cancer

mRNA technology is positioned to be used not only as a prophylactic for infectious diseases like COVID-19, but also as a therapeutic treatment for cancer.

In contrast to infectious vaccines, where knowing the viral DNA sequence is sufficient to develop a universal vaccine, for cancer mRNA vaccine it is necessary to sequence the DNA of the patient’s healthy and cancerous cells.

The  comparison between the DNA sequences of healthy and cancerous cells determines one or more mutated proteins — or antigens — that are only found in the cancer cells. The mRNA in the cancer vaccine can be developed to carry the sequence of those antigens.

“There are a few critical things to take in consideration when switching from infectious disease to cancer vaccines,” says Shi. “The first one is that we know the sequence of every viral protein, while in cancer it could be many proteins that carry mutations. The selection of the antigen(s) to use is critically important for the success of the cancer vaccine. To develop a successful cancer vaccine, you have to come with the right antigen, or even a few antigens, depending on the type of cancer to treat.”

When the patient receives the mRNA vaccine, their immune cells start expressing the antigen and activate T cells. Then, those activated T cells kill the tumor cells expressing those same antigens, fighting the cancer.

This kind of technology is a personalized therapy, since mutations could vary between patients,  depending on the cancer type. A 2020 study applied DNA sequencing and tumor-infiltrating lymphocytes to identify specific mutations present in gastrointestinal cancer patient’s tumors. Using this data, the research team developed a mRNA construct incorporating defined neoantigens, predicted neoepitopes and specific mutations of driver genes. The construct was administered to four patients and the immunological response observed. It was found to elicit mutation-specific T cell responses against the predicted neoepitopes.

Today, many other similar therapies are being tested in clinical trials. Bioplatforms are indispensable to developing personalized therapies, because once the bioplatform is in place and the technology is developed and tested for one particular case, then selecting the antigen(s) for each patient will be sufficient to develop the therapy for each individual.

mRNA-based therapies for everybody

The COVID-19 pandemic highlighted the key difficulties that third-world countries face when accessing vaccines. As a result, the World Health Organization created the mRNA technology transfer hub.

The mRNA hub is a global bioplatform that shares knowledge and technology between low-income countries to help them produce state-of-the-art therapies for their population. The immediate goal is to develop mRNA COVID-19 vaccines to distribute among countries in need. As of April 2022, the WHO selected several low- and middle-income countries to take part in this collaborative project, including Argentina, Brazil, South Africa and South Korea, and there’s plans to add more countries in the future.

“The participation within the mRNA hub opens new paths for innovative product development,” says Fernando Lobos, business development director at Sinergium Biotech, one of the companies involved in the mRNA hub. “We are adding specialized staff, acquiring new equipment and collaborating with other hub’s partners, including the WHO, the Pan American Health Organization, the Medicine Patent Pool and PATH.”

The international and collective strategy that the mRNA hub is creating won’t be limited to COVID-19 vaccines development. The hub plans to develop vaccines for other infectious disease and cancers, making use of the mRNA bioplatform.

“This is a lot more than just a project focused on COVID-19 vaccines,” says Lobos. “The mRNA hub is creating a collaborative network, sharing the latest technology within poor countries. This will strongly impact on improving mRNA vaccine availability to people from those regions.”

With bioplatforms, the process of developing and manufacturing safe and effective mRNA vaccines — either for infectious diseases or cancer — is extremely efficient when compared to manufacturing a classical vaccine from scratch. Bioplatforms allow mRNA technology to be transferable and reusable, accelerating the development of innovative vaccines. The mRNA revolution we are living in would not be possible — or at least that revolutionary — without the existence of bioplatforms.