It has been nearly four years since Americans began getting vaccinated for COVID-19. Vaccines made from messenger ribonucleic acid (mRNA) have been credited with saving countless lives. Now the race is on to sequence all RNA molecules, which scientists say carries the potential for countless medical breakthroughs.
“Everybody knows what DNA is and RNA was sort of like the distant cousin that nobody wanted to talk about,” said Juan Alfonzo, a professor of molecular biology, cell biology and biochemistry at Brown University.
Alfonzo said the pandemic got more people talking about RNA — molecules that take genetic information found in DNA and turn it into processes, like making proteins. Take the current COVID-19 vaccines, for example. It was RNA that taught cells how to quickly trigger an immune response to the coronavirus. Alfonzo said the vaccines just scratch the surface of what is possible with RNA.
“We’re all thinking ‘OK, if that one RNA did it, what about the other millions of RNA molecules that we can even manipulate in a lab and make them do something new?’” he said.
Alfonzo is the executive director of Brown University’s RNA Center in Providence. He wants Brown University and Rhode Island as a whole to become a major hub for RNA research nationwide. He said there is a lot of interest from students who want to pursue the field.
“It’s like computer science in the 1980s,” he said. “Everybody wanted to be a computer scientist. And with RNA right now, it’s like that. It’s like everybody, ‘Oh, RNA, I’m interested.’”
The unknowns of RNA
Much remains unknown about these molecules. Alfonzo said scientists do not know the function of most RNA and, adding to the mystery, there are more than 180 known RNA modifications.
When asked if a shortcoming in technology is the reason why the function of most RNA remains unknown, Alfonzo said that’s part of it.
“It’s not just technology,” he said. “I mean technology guides discovery but ideas drive technology.”
Alfonzo is part of a nationwide network of researchers with an ambitious idea known as the Human RNome Project — to sequence all of the RNA in human cells and map all the modifications. It is the RNA equivalent of the Human Genome Project, which sequenced human DNA.
“Think of RNA as a future in better health care, cheaper health care,” said Dr. Vivian Cheung, a professor of pediatrics at the University of Michigan. She is joining the faculty at Brown University in the fall. She is eager to learn the order of the building blocks that make up all RNA molecules. Cheung said current technology to sequence RNA does not go far enough. She likens it to reading a book where many of the letters are missing.
“That’s exactly how we’re reading RNA today,” Cheung said. “We’re missing many of the modification or missing most of the letters. So we don’t know. We cannot read it completely and it’s very hard to copy it to make medicine.”
Potential uses of RNA
Cheung and other researchers briefed congressional staff earlier this year on the potential uses of RNA, including as medicine for many diseases currently without treatments. But they say they need the federal government’s help to make it happen.
“It’s not so astronomical that it’s not within reach, but we really need leadership and national infrastructure to make this possible,” Cheung said during a congressional hearing on May 8, 2024.
Researchers said RNA vaccines are being developed for malaria, tuberculosis, various cancers and allergies. RNA is already being used as a defense against plant pathogens and to help crops increase their yields.
“It seems that we should and must be able to read the RNA that is in every single one of our cells and we have already seen the future of what it can be,” Cheung said.
Federal government’s role in RNA research
U.S. Sen. Jack Reed, D-RI, is pushing for the United States to take the lead on RNA research.
“As a nation, it is essential we maintain our global leadership to harness this tool for good,” Reed said during the May 2024 hearing.
With every breakthrough, Reed said there is the potential for misuse. Scientists said that could include creating viruses that harm our food supply and even humans.
“There’s a first-person advantage because, one, you have the technology and you can use it for good, we hope, but also for ill,” Reed said. “We’ve seen this throughout history. We were able to develop nuclear weapons before everyone else.
“I think if another country had gotten it first, it would not have ended up the way it did.”
Road map to sequence RNA
A report from the National Academies of Sciences, Engineering and Medicine published earlier this year offers a road map to sequence RNA. The report calls on federal entities to get involved to advance the research and technology.
When asked where things stand with Congress, Reed said, “Congress has not yet, I think, carved out a specific role and designated a specific agency. I must say one of the things that we’ve been really spending a lot of time in is artificial intelligence … I think RNA is waiting to be elevated to this level.”
Rhode Island is working to bring that research to the forefront. The state is growing its life science industry, which includes RNA.
Neil Steinberg is helping to lead the effort. He is the chair of the Rhode Island Life Science Hub, a quasi-state agency tasked with strengthening the sector.
“Many years ago, earlier in my career, we had two primary industries in Rhode Island, jewelry and textiles,” Steinberg said. “For a variety of reasons, they left … and we haven’t really replaced those.”
One of Steinberg’s priorities is creating laboratory space in Rhode Island.
“We have no commercial lab space here. The universities have it. The hospitals have it. So if you and I started a company today and we needed lab space, it does not exist in Rhode Island,” Steinberg said. “We’d have to go to Cambridge.”
Philanthropic organizations like the Warren Alpert Foundation are also throwing their support behind RNA initiatives. Gus Schiesser is the organization’s executive director.
“The foundation likes to take big swings at high-reward projects like this study that have the potential for countless medical breakthroughs,” Schiesser said.
In 2022, the foundation awarded the National Academy of Sciences $1 million to develop a road map to sequence all of the RNA in human cells.
“We’re hoping that the RNome project is like the Genome Project and the sequencing of RNA is going to lead to so many cures and treatments of diseases,” Schiesser said.
Changing the world
Cheung said RNA technology can improve the world if leaders can get future scientists excited about the work.
“In order for RNA to become the bio future … for agriculture, for health, for data storage, for biodefense, we need people to work in these different sectors,” Cheung said.
Reed said the U.S. does not need to go at this alone. He supports working with countries that are already funding RNA research, including Canada, Germany and Australia.
“We can collaborate closely with them and we can coordinate with them, and they are trusted allies in so many different ways,” Reed said.
At Brown University, Alfonzo said it is important to seize on the momentum brought on by the pandemic.
“It is a moment in time with RNA where not only the scientists are engaged, but the public is engaged. And that is unique, I think,” Alfonzo said.
Researchers estimate it will take about 15 years to develop the technology needed to sequence any RNA molecule with all its modifications.
