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Recently, Science Media GEN spoke with Professor Robert Langer of the David H.Koch Institute at MIT about the present and future of mRNA vaccines as Moderna’s co-founder.

GEN: The technology behind mRNA vaccines has been around for decades, but it was only during the pandemic that a publicly available mRNA vaccine was first seen. Why wasn’t it released earlier?

Langer: While hundreds of scientists have indeed worked on developing mRNA vaccines and therapeutics over the past three decades, the COVID-19 pandemic has accelerated the creation of effective and commercially viable mRNA vaccines, resulting in breakthroughs.

In fact, in late 2019 and early 2020, when the COVID-19 crisis began, some companies like Moderna, BioNtech, and Curevac were also conducting clinical trials of multiple different vaccines and treatments. At the time Moderna had eight vaccines in human clinical trials (including a personalized cancer vaccine, a vaccine against Zika, and a dual vaccine against metapneumovirus and a parainfluenza virus). Moderna sees a once-in-a-lifetime opportunity by leveraging mRNA tools and technologies that can quickly meet the global demand for COVID-19 vaccines, with all the necessary conditions in place, such as the right mRNA chemistry and nanocarriers for mRNA protection. Therefore, we are bringing COVID-19 mRNA vaccines to patients as soon as possible without compromising public safety. Moderna scientists identified the ideal candidate protein on the coronavirus SARS-CoV-2 virus (spike protein), identified the mRNA sequence required to encode the protein, and received FDA approval to proceed six months later.

Compared with traditional vaccines, mRNA has the advantages of rapidly updating vaccines as new variants emerge, developing combination vaccines to fight multiple variants (and pathogens) simultaneously, and rapidly expanding to serve a global population, which prompted scientists to use it against SARS-CoV-2.

At the same time, Moderna’s mRNA platform produces antigens with higher biological fidelity and higher success rates than conventional vaccines — all in record time. MRNA vaccines do not require a huge manufacturing plant to produce, but can be produced in the same location through the same process.

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GEN: What other diseases or conditions can mRNA vaccines provide protection against?

Langer: Moderna currently has mRNA vaccines in development to reduce latent viruses such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV), as well as an integrated mRNA vaccine for COVID-19, seasonal influenza, and respiratory syncytial virus (RSV). Moderna is also planning to develop mRNA vaccines that could once and for all defeat herpes simplex virus (HSV), multiple sclerosis (MS), cancer, and HIV.

MRNA vaccines can provide protection against almost any viral or bacterial infection. Unlike traditional vaccines, mRNA vaccines enable the patient’s own cells to “train” the immune system to recognize pathogens by producing invader proteins that the immune system needs to attack. Thus, mRNA vaccines are limited only by the immune system’s own ability to fight pathogens. Once ideal candidate proteins have been identified, identifying the mrnas required to encode these proteins is a relatively straightforward process.

GEN: Can mRNA vaccines provide universal protection against a range of viruses such as coronavirus?

Langer: That’s right. Antimicrobial and antibiotic resistance is a natural evolutionary process that results from genetic variation and pathogen mutations that create new traits, which allow organisms with resistant traits to naturally survive and thrive.

First, mRNA vaccines have the potential to help combat antimicrobials and antibiotic resistance by reducing reliance on traditional antibiotics. In addition, Moderna’s mRNA platform helps combat drug resistance by identifying the most desirable and persistent targeted antigens, by improving the prediction of new strains, and by accelerating vaccine production to defeat these strains. Finally, by training the immune system to look for specific surface proteins on bacteria, mRNA vaccines target specific pathogens more effectively, while avoiding the problem of damaging a patient’s “good” bacteria with increasingly virulent antibiotics. For example, mRNA vaccines against drug-resistant malaria strains have yielded encouraging results by selecting “coat proteins” as target antigens.

GEN: Overall, mRNA vaccines are safer, more effective, and easier to produce than conventional vaccines. But as with all technologies, there is always room for improvement in terms of accessibility, affordability, effectiveness and security. Cold storage requirements and side effects, as well as possible allergic reactions, are some of the issues that affect the use of these vaccines. Have researchers developed solutions to these (or any other) problems?

Langer: Moderna is using artificial intelligence and machine learning to make vaccines safer, more durable, and easier to refrigerate storage conditions by minimizing the length of mRNA chains. The mRNA Access Initiative aims to accelerate the creation of novel mRNA vaccines through collaboration with global partners. MRNA Access enables outside researchers to leverage Moderna’s platform to develop mRNA vaccines against emerging and neglected infectious diseases around the world. This strategy has multiplied our brain trust and led to ten-year supply agreements with strategic countries, which will lead to safer and more effective vaccines. At the same time, Moderna is expanding its patent-free COVID-19 vaccine technology to 92 additional low – and middle-income countries and setting up an mRNA manufacturing facility in Kenya. In addition, we are working at MIT on how to make a self-boosting vaccine that can be given in a single dose, without the need for a booster; And developing more stable nanoparticles and microneedle patches that can be delivered stably around the world.

GEN: There has been talk recently about whether a pill or nasal spray vaccine could be developed. Is this delivery method applicable to mRNA vaccines?

Langer: As long as an appropriate and effective delivery mechanism can be found to protect mRNA from the current environment (mucus, saliva, stomach acid) while facilitating mRNA delivery into cells, the possibilities for vaccine delivery are endless. While the gold standard for vaccine administration is intramuscular injection through the arm, intranasal COVID-19 vaccines have been shown to elicit strong cellular immune responses in humans.

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GEN: What other ways do you think mRNA vaccine technology can improve human well-being?

Langer: I think it’s important to realize that there are almost no limits. Whether it’s mRNA vaccines or anything else, I always tell my students to dream big dreams, dreams that can change the world. But if you do, you may run into obstacles. When I first discovered a way to deliver large molecules, including nucleic acids, from small particles, I was ridiculed by the scientific community. I was turned down for my first nine research grants, and no engineering department in the world would hire me as a faculty member. But I didn’t give up, and I always tell my students never to give up either.


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