We Need an mRNA Champion in a Red Cape

I grew up in an era of Superman comic books.

Superman captivated the imagination of a generation of kids like me. It told stories of an otherwise ordinary human who could achieve extraordinary feats of speed and strength, leaping tall buildings with a single bound, to defeat the bad guys. Miracles could happen on a foundation of truth and justice, and that this was “the American way.”

Superman, of course, was a work of fiction. Kryptonite isn’t in the periodic table. But the optimistic narrative proved true over the course of my career in science. I have seen numerous medical miracles in my life, many of them starting in a lab.

CAR T cells to fight blood cancers; anti-cholesterol drugs for prevention of heart disease; ways to dissolve clots from strokes; gene therapies for genetic diseases; antisense RNA for treatment of eye and liver disease; and yes, mRNA vaccines for COVID. One of the greatest miracle technologies in the last few years has been the rapid expansion of mRNA vaccines and treatments.

Using mRNA to deliver a therapy to a cell or to produce an antigen to show the immune system what to defend the body against—a bounding leap of scientific advancement—has, largely to our dismay, been accompanied by an anti-science backlash.

Proposals are bubbling up around the country—Montana, Florida, Idaho, and Texas—to ban or restrict use of the technology, including some products already FDA approved. Scientists seeking grants to support their research are being advised to scrub the language “mRNA” from their grant proposals.

These ideas ignore a mountain of evidence supporting mRNA’s potential for medical advances in a wide variety of diseases. These gains were made through the federal government’s enormous investment in basic research. Scientists have been working painstakingly on the mRNA molecule since its discovery in the 1960s.

The journey for mRNA vaccines started in the early 1990s and culminated in the successful COVID-19 vaccines of 2020. Katalin Karikó and Drew Weissman won the Nobel Prize in 2023 for work that paved the way for the mRNA vaccines. Three to four billion doses were administered worldwide and these vaccines are widely acknowledged to have saved over a million lives in our country.

It’s true that viral escape has resulted in the reduction of efficacy against symptomatic disease. But in the elderly population most vulnerable to COVID, mRNA COVID-19 booster vaccines have low side effects and continue to reduce the risk of Emergency Room visits, hospitalization and death. The extension of mRNA technology to other respiratory diseases and viral infections such as cytomegalovirus and herpes simplex viruses are under investigation.

Why mRNA Matters for Vaccine Development

The mRNA technology is uniquely promising for developing new vaccines because of how quickly it can be designed and scaled up. Previous technologies would have taken too much time or money to effectively defend people against a fast-moving infectious disease.

The beauty of RNA is its price, its simplicity, its ability to be duplicated, and its iterative potential.

In my field of HIV vaccines, where we use mRNA in structure-based design, it’s a game changer. One can produce an mRNA vaccine for a Phase I clinical trial, to evaluate safety at a variety of doses, for about $1 million. That modest budget allows us to use rigorous protocols for GMP (Good Manufacturing Practices), and still have a candidate vaccine ready in four to six months, or even as fast as 70 days in a pandemic.

To train the immune system against this notoriously wily virus, we need four separate vaccinations, and we have two or three choices as to what might be the best structure for each vaccine prototype. The ability to quickly design and iterate mRNA gives us the options we need to keep making tweaks to come up with the optimal combination of structures and sequence of shots.

We have also used protein-based vaccines extensively, but making a protein vaccine usually takes three times as long and triple the budget. More than $4 million is needed to produce a small batch for early vaccine trials, and it usually takes 12 to 15 months to manufacture.

About 30 to 40 percent of the time, after all this time and expense on manufacturing runs, we come away empty handed and unable to run the trials. That’s because the protein cannot always be predicted to fold exactly or be well stabilized when manufactured.

Protein-based vaccines, when properly conceived and folded, can have advantages over mRNA for population-based control because they have a long shelf life and only require basic refrigeration. But those advantages only kick in once you know what to make and how you are making it.

We need mRNA for the research enterprise. That does not mean it will always emerge as the technology used in the global rollout of a product like a vaccine. One could use mRNA in discovery to identify the right protein components, then switch to a conventional protein subunit vaccine.

New Directions for mRNA Therapies

The speed and modularity of mRNA for vaccine research is also useful for research into cancer and autoimmune disease. The long list of potential indications includes malignant melanoma, brain cancer, liver disease, colon cancer, interstitial lung disease; and many genetic diseases. One of the most impressive late-stage developments is mRNA for use in personalized cancer vaccines to prevent the cancer from spreading.

A new generation of startups have emerged to develop second-, third-, and fourth-generation mRNA vaccine products—to make the lipid nanoparticles specific for a target organ; to get rid of the lipid nanoparticle; to decrease the amount of toxicity; to improve the transcription of RNA so there’s greater potency; and just to develop immunotherapies to deliver intracellularly what before now has not been possible. It’s as if the mRNA vaccine allowed the mRNA technology to reach a threshold to expand its use exponentially—a potentially transformative tool in health care worldwide.

The Opposition

Why are we seeing such a strong backlash? From both a health-care perspective and an economic standpoint, it makes no sense. The gap is wide between the scientific publications and what is pushed out on the dark web. There’s a cynicism that says everything in the research sector is wrong. Why has this gone so far? Why can’t we easily explain that mRNA doesn’t alter your DNA? It stays in the cytoplasm and doesn’t get into the nucleus. God designed it so it couldn’t get to your DNA.

How can the business community, which has so much invested in this, not challenge the political tsunami threatening to overwhelm the achievements of science?

Why aren’t they out there telling the science side? Are they working “behind the scenes” out of fear of retribution? What’s the fear?

Shouldn’t the greater fear be that we don’t deliver what we know we can? That people will die or have incredible morbidity by not having access to a discovery that can alter their lives?

Fear remains our greatest foe in this American tale. What’s happened to truth, justice, and the American way?

Looks like we need an mRNA champion with a red cape.