Report lays out road map to transform understanding of RNA and invest in RNA science and biotechnology

new report from the National Academies of Sciences, Engineering, and Medicine provides a road map to develop the capacity to sequence any RNA molecule from any biological system with all its modifications. The report provides priorities and milestones for a 15-year initiative to advance technology, centralize data resources, expand research and develop standards, and cultivate a skilled workforce in the field.

The core of the proposed initiative is an overarching, strategic U.S. government effort and coordinated investment in the study and mapping of RNA modifications, led by an established oversight body, such as the White House Office of Science and Technology Policy. The impacts could span far beyond biomedical sciences and health, so the report calls on key federal entities such as the National Institutes of Health, National Science Foundation, National Institute of Standards and Technology, and the U.S. departments of Defense and Energy to collaborate with academia, industry, philanthropic organizations, and international partners to drive innovation.

RNA calls DNA into action in all living cells by transferring instructions from DNA in the nucleus to the cytoplasm where proteins are made. Every cell in every organism has a different set of modified RNA molecules that make up its epitranscriptome. Epitranscriptomes are constantly changing as cells develop and respond to their environment.

Currently, without knowing the exact composition of all RNA molecules that derive from each gene, researchers’ ability to understand the molecular underpinnings of health and disease is severely limited. RNA can act as an indicator about a patient’s health, is a potential pathway for delivering treatments, and provides real-time information about what is changing and happening in an organism. The report charts a course for developing technologies and infrastructure that would enable the determination of any epitranscriptome of scientific and public interest.

Although research exploring how RNA modifications affect biological systems is still in its early stages, an increased understanding of RNA in recent years has already produced useful biotechnologies. Most notably, scientists harnessed decades of mRNA research to quickly produce a COVID vaccine that has saved millions of lives. The 2023 Nobel Prize in physiology or medicine was awarded to the researchers whose early work studying RNA modifications for use in mRNA vaccines laid the foundation for this critical breakthrough. Potentially transformative applications for cancer therapies using RNA are already in clinical trials, and, beyond potential health and medicine applications, RNA modifications also show promise for enhancing agricultural productivity and other bio-based industries.

“Increased scientific understanding of RNA has already saved millions of lives and changed society for the better,” said Taekjip Ha, professor of pediatrics at Harvard Medical School and Boston Children’s Hospital, and co-chair of the committee that wrote the report. “How we are using RNA now barely scratches the surface of how these technologies may be used in the future.”

Past large-scale scientific efforts, like the Human Genome Project, have shown that focused organization, collaboration, and funding directed toward a set of well-defined goals can accelerate technological advancement for the greater good. The report indicates that a concerted investment of time, effort, and funding by key public and private groups will lead to the development of technologies and computational tools capable of identifying and determining the location and abundance of all RNA modifications in a single experiment within 15 years, which could drive advances in other critical sectors of societal and national interest.

“All major sectors — including health and medicine, agriculture, energy, commerce, defense, and national security — stand to benefit from a better understanding of RNA modifications,” said committee co-chair Brenda Bass, a distinguished professor in the department of biochemistry at the University of Utah. “There is a huge section of the bioeconomy just waiting to be unlocked, but it needs a coordinated effort and investment from public and private sectors to be realized.”

“The past several decades have included a remarkable trend toward precision medicine, driven by groundbreaking efforts such as the sequencing and mapping of the human genome, but we now know that our genetic code alone doesn’t tell the whole story,” said Victor J. Dzau, president of the National Academy of Medicine. “Understanding RNA modifications and harnessing this knowledge holds immense potential — not only for human health and medicine but also for shaping all living systems and the products and technologies stemming from them.”

The report recommends that an established oversight body coordinate and catalyze a large-scale epitranscriptomics initiative, with an extensive implementation plan building on expertise from the health, science, agriculture, commerce, energy, national security, and defense sectors. The report outlines key focus areas where infrastructure and technology can be improved for the study of epitranscriptomes and provides conclusions and recommendations in each area.

Key efforts to unlock any epitranscriptome

rna-seq

  • Expanding Research: Ongoing research in the field of RNA modifications needs to continue and expand. Increased recognition of the importance of RNA modifications in health, and their broad application potential for diagnosis, treatment, and prevention of disease, will fuel technological advances that can benefit other fields.
  • Advancing Technology: Federal funders of research, such as NIH, NSF, DOD, and DOE, should invest in and prioritize closing gaps in the existing tools, exploring new technologies, and centralizing resources for available tools and methods.
  • Developing Standards and Centralizing Data: NIST should develop, curate, and promote standards to support the field, especially RNA reference materials, which should be developed with a focus on accessibility. NIH should establish and maintain a sustainably funded and centrally managed database that maintains up-to-date, curated information about RNAs and their modifications. NIH should collaborate with international partners, and the National Center for Biotechnology Information should then establish and promote standards for databases, data exchange, and nomenclature for RNA modifications.
  • Cultivating a Workforce: To develop a strong workforce, institutions and funding agencies, in partnership with education experts, scientific societies, and industry groups, should build upon existing educational materials and training opportunities for students and the public. The materials and opportunities should be age appropriate and engaging for the interests of different groups, while covering the basic biological and chemical principles of RNA modifications, the tools available for their study, and their potential application in future medicines and useful biotechnologies.

The study — undertaken by the Toward Sequencing and Mapping of RNA Modifications Committee — was sponsored by the Warren Alpert Foundation and the National Institutes of Health.

SourceNational Academies of Sciences, Engineering, and Medicine

Leave a Reply

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

*

Time limit is exhausted. Please reload CAPTCHA.