In a ‘transformative moment in medical research,’ Human RNome Project launches at Brown

The Warren Alpert Medical School hosted the first international working group meeting for a project that aims to sequence all of humanity’s RNA, mirroring the approach of the Human Genome Project in the 1990s.

The COVID-19 vaccines by Pfizer-BioNTech and Moderna were possible due to a modification to the messenger RNA molecule — just one example, scientists say, of the game-changing potential of RNA biology and therapeutics. Photo by Nick Dentamaro.

In late January, RNA scientists from across the world gathered at Brown University’s Warren Alpert Medical School to roll up their sleeves and get to work on a venture that many say could be more exhaustive and more daunting than the Human Genome Project.

But the outcome of this effort, known as the Human RNome Project, could also be even more consequential for human health, offering clues to develop vaccines, unlock mysteries behind rare diseases and discover treatments for some of humanity’s most intractable illnesses, like Alzheimer’s disease, diabetes and many cancers.

Single-stranded ribonucleic acid is present in all living cells. The Human RNome Project aims to identify and quantify all RNAs and map their modifications, in both normal and diseased human cells and tissues.

Dr. Mukesh K. Jain, Brown’s dean of medicine and biological sciences and senior vice president for health affairs, offered to host the workshop, the first international effort focused on the RNome, in part to highlight Brown’s growing commitment to RNA research.

“The Human RNome Project is truly a transformative opportunity, one that promises to enormously enhance our ability to develop novel diagnostics and therapeutics for diseases that still burden society,” Jain said. “Brown is investing heavily in strengthening our RNA research capabilities, to establish this as a signature program for the University.”

The RNome mission is complicated by a lack of technology that can accurately read RNA molecules and, specifically, their modifications: tiny tweaks to the nucleotides that are critical to an RNA’s function. The COVID-19 vaccine, for example, was only possible due to a modification to the messenger RNA molecule.

There are at least 170 known modifications, said workshop co-organizer Dr. Peter Dedon, a professor of biological engineering at the Massachusetts Institute of Technology, who leads research groups in Cambridge, Massachusetts, and in Singapore.

“Everything’s got a modification,” Dedon said. “And that means they can get screwed up in many different ways [to cause] disease.”

But researchers don’t know what many of those modifications do — or even the purpose of many RNA molecules. The Human Genome Project found that humans have 65,000 total genes, Dedon said, only 20,000 of which code for mRNA, which makes proteins. The rest code for RNAs of varying and often unknown functions.

“This is a mess — it’s a wonderful mess,” Dedon said in welcome remarks to his colleagues.

According to conference attendees, figuring out the function and purpose of human RNA molecules will transform biomedical research and human health.

“This work, the Human RNome Project, has the potential to improve our understanding of disease and to advance therapeutics to better serve patients for generations to come,” said U.S. Senator Jack Reed, who spoke to the scientists via Zoom. “It truly is a transformative moment in medical research and medical investigation. And we have to seize that moment.”

A global RNA hub at Brown

Brown is home to the new Brown RNA Center, staffed by numerous experts in the field and led by Juan Alfonzo, a professor of molecular biology, cell biology and biochemistry.

“I am jealous as hell of everything that’s happening down here and the infrastructure that’s being built and what Juan Alfonzo is doing now to create a big program across the campus,” Dedon said.

Shortly after becoming dean in 2022, Jain noted that RNA biology would be a research priority for Brown’s Division of Biology and Medicine. But even before his arrival on campus, Jain urged the Warren Alpert Foundation — which had awarded the 2022 Warren Alpert Prize to the scientists behind the COVID vaccine, two of whom later went on to win the Nobel Prize — to support the RNome project, telling them it was a “once-in-a-lifetime opportunity” to get in on the ground floor of something truly transformative.

“It piqued our interest, because of our mission as a foundation, which overlaps 99.9% with the RNome project,” said Warren Alpert Foundation Chair David M. Hirsch. “The Human RNome Project is one of the most ambitious scientific endeavors of our time.”

In addition to January’s workshop, the foundation has funded RNA research and a National Academies of Science, Engineering and Medicine committee report that includes Alfonzo and is developing a roadmap to sequence the RNome.

The RNome working groups will carry out the “marching orders” of the NASEM white paper, said Dr. Vivian Cheung, a pediatric neurologist and RNA biologist from the University of Michigan who served as lead organizer of the three-day working group meeting.

The workshop participants were divided into four groups, each tasked with coming up with recommendations to tackle the biggest issues related to the RNome, from necessary technologies to workforce development. After the workshop, Cheung said each group emerged with a to-do list.

“I was really surprised how enthusiastic people were and how willing they are to start working,” she said, adding that the groups will meet at least monthly and that more people will get involved as time goes on.

“The Human Genome Project had several of these planning meetings, and they have become famous by the location where they were done,” Cheung said. “There was a Bermuda convention, a Fort Lauderdale meeting… So we’re hoping that this will become the ‘Rhode Island meeting.’”

Workshop participant Frederick L. Tyson is a program director at the National Institute of Environmental Health Sciences, where he’s been working to support projects that investigate the regulatory roles of RNAs in environmental exposures. When Tyson learned from Cheung about the enormous potential for human health that a fully sequenced RNome would bring, he wanted to be a part of the effort.

“If we’re able to really develop new technologies and resources that are being called for by the RNA community, and if we’re able to develop these effectively and successfully, it’ll really catalyze a kind of revolutionary advance, both in the way we’re able to conduct basic research, but also in clinical applications that are going to use RNA-based therapeutics,” Tyson said. “I hope that almost everyone on the globe that went and got vaccinated [against COVID] can appreciate not only the importance, but the impact that this can have.”

While the NIH may be able to offer some support for the Human RNome Project, Tyson said, fully funding the enterprise will require congressional approval, not to mention investments from governments around the world. Mark Helm, the workshop’s third co-organizer, came to Providence from Mainz, Germany — the hometown of BioNTech, which partnered with Pfizer to create an mRNA COVID vaccine.

“Europe looks to the U.S. to take the initiative here,” Helm said. “We would, as Europeans, greatly profit from this if we could do this together. It would be a lot easier for us to talk to our governments and the funding agencies to fork up some money.”

The ultimate goal of the working group is a publication laying out how the Human RNome Project will be implemented. Like the Human Genome Project, it will require the participation of government agencies, academic institutions and private entities, and will likely take decades to complete. The “Rhode Island meeting” was just the first step in what all the participants hope will be a victorious ultramarathon.

“It’s not going to be easy,” Tyson said, “but you have to start somewhere.”

SourceBrown University

Leave a Reply

Your email address will not be published. Required fields are marked *

*

Time limit is exhausted. Please reload CAPTCHA.