mRNA Technologies: A Primer

Decades of research on messenger RNA (mRNA) and related technologies enabled the rapid development of the Pfizer/BioNTech and Moderna Coronavirus Disease 2019 (COVID-19) vaccines. Some experts believe that this success portends a revolution in medicine that will bring better pandemic preparedness and new treatments for disease. This rapid progress may present questions for congressional consideration. For example, what is the appropriate role for the federal government in supporting and coordinating mRNA-related research and development (R&D)? Messenger RNA is a biological molecule whose central role in cellular protein production makes it an attractive target for a host of medical treatments and vaccines. The COVID-19 mRNA vaccines represent the first Food and Drug Administration-approved uses of mRNA-based technology. Vaccines against Human Immunodeficiency Virus (HIV), rabies, and influenza and treatments for cancer and certain rare diseases are in clinical trials. At the same time, mRNA research and the development of other, more-wide ranging, uses of this technology face challenges, including potential undesired immune responses to repeated treatments, complications with targeting the appropriate tissue, and the need to protect the mRNA from premature degradation. The federal government, largely through the National Institutes of Health (NIH) and the Defense Advanced Research Projects Agency (DARPA), has invested billions of dollars in R&D of mRNA and related technologies. Despite the research challenges facing further commercial applications, several groups project mRNA-related revenue to increase by a compound annual growth rate of between 10% and 90% over the next 5 to 10 years. Consistent with these growth projections, private investments are being made by and in companies of varying size and technology maturity that are conducting mRNA R&D. The potential future benefits of mRNA technology and the lessons learned during past R&D on this technology raise some possible issues for Congress: In addition to funding the foundational basic research that led to this technology, the federal government shifted its support during the COVID-19 pandemic to include activities generally left to the private sector, such as late-stage clinical trials and research, product development, and manufacturing. The appropriate role of the federal government in late-stage R&D is not a new issue; however, the pandemic would mark an inflection point if Congress were to continue increased support for such activities. The difficulty faced by some researchers in obtaining funding for what, in retrospect, were crucial fundamental studies raises questions about whether NIH’s committee-based peer review process adequately funds “high-risk, high-reward” projects. Support for high-risk, high-reward research is considered an important element in developing breakthrough technologies that address societal challenges, including health-related challenges, and in maintaining the economic competitiveness of the United States. Congress may have already taken steps to address this through the $1 billion it appropriated for FY2022 to establish the Advanced Research Projects Agency for Health (ARPA-H) in the Department of Health and Human Services (HHS). ARPA-H is modeled after DARPA in its approach to funding high-risk, high-reward research. Apart from directly setting the level of support for mRNA technology R&D, Congress may consider options such as facilitating coordination of this research or providing for a technological research plan. If the U.S. seeks to maintain its global leadership role in the life sciences broadly, and in mRNA technologies specifically, then Congress would likely face consideration of how to ensure the implementation of robust federal policies, which may include increased federal R&D funding; an effective regulatory environment; a well-trained and adequate life sciences workforce; and public and private sector coordination.