Possibilities for RNA Therapies Seemingly Limitless

Thanks to the COVID-19 vaccines, messenger RNA (mRNA) went from "a technology looking for a disease" to a global phenomenon in the last few years, and it could soon find its way into treatments for cancer, heart conditions, and more.

“Before COVID and the vaccines, there were a handful of biotech companies doing RNA work,” said Drew Weissman, MD, PhD, a professor at Penn Medicine and Director of the Penn Institute for RNA Innovation, whose work was the basis of the SARS-CoV-2 vaccines. “There was funding available, but it wasn’t overwhelming like it is nowadays.”

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Thanks to the success of Moderna and BioNTech’s COVID-19 vaccines, however, that all has changed. The question is now where the limits of RNA technology lie.

“The likelihood of success seems much higher and more certain just because of what we saw with the COVID vaccines,” said Margery Fischbein, Managing Director of Cassel Salpeter’s healthcare practice. “We may be on the verge of a whole new area opening up for this technology that just a few years ago people weren’t sure what to do with.”

In November 2012, CureVac researchers published the first proof-of-concept for the technology, touting the results of an mRNA-based influenza vaccine in mice, pigs, and ferrets in a paper in Nature. Prior to that, it was thought by many scientists that mRNA would be too unstable to use as a vaccine against infectious disease.

Now, mRNA-based vaccines are being developed that can train the body to recognize and deactivate proteins involved in a parasite’s lifecycle, which is the mechanism behind a new, two-part malaria vaccine co-developed by the labs of Weissman and Nirbhay Kumar, PhD, at George Washington University.

Meanwhile, because the body more readily mounts an immune response to foreign targets than it does to host cells that have turned cancerous, developing cancer vaccines is more difficult than creating vaccines that work against infectious disease. However, such a vaccine would surely be considered the Holy Grail of oncology. And progress is being made.

In December 2022, Moderna announced that a cancer vaccine candidate it had developed with Merck cut down on melanoma recurrence in a phase 2 clinical trial when combined with Keytruda. Meanwhile, BioNTech has seen progress with a personalized mRNA vaccine for pancreatic cancer. And Gritstone reported early success against solid tumors from its self-amplifying mRNA (samRNA) vaccine.

For 2023, BioNTech has five clinical trials planned for mRNA vaccines — some in collaboration with Pfizer — against infectious disease including HSV-2, shingles, tuberculosis, malaria, and influenza. And Moderna is also working on its own vaccine for HSV and many other infectious disease.

Many more diseases, such as bone marrow diseases, Bubble Boy syndromes, genetic liver diseases, and immune deficiencies, could be combated with RNA, too, and could all see new RNA-based treatments in the coming years, according to Weissman.

“It really has very wide applications,” Weissman added. “We’ve lost count of how many diseases we thought RNA could be useful for, but it’s quite a few.”