PROVIDENCE, R.I. [Brown University] — 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.