Gain-of-function (GOF) studies, or research that improves the ability of a pathogen to cause disease, help define the fundamental nature of human-pathogen interactions, thereby enabling assessment of the pandemic potential of emerging infectious agents, informing public health and preparedness efforts, and furthering medical countermeasure development.
Gain-of-function studies may entail biosafety and biosecurity risks; therefore, the risks and benefits of gain-of function research must be evaluated, both in the context of recent U.S. biosafety incidents and to keep pace with new technological developments, in order to determine which types of studies should go forward and under what conditions.
To address the biosafety and biosecurity risks associated with undertaking such research and ensure that they are adequately considered and appropriately mitigated to safely realize the potential benefits, the Department of Health and Human Services (HHS) adopted a pre-funding review mechanism in 2017. The HHS Framework for Guiding Funding Decisions about Proposed Research Involving Enhanced Potential Pandemic Pathogens (P3CO) is intended to guide HHS funding decisions on proposed research that is reasonably anticipated to create, transfer, or use PPPs resulting from the enhancement of a pathogen’s transmissibility or virulence in humans (enhanced PPPs). Enhanced PPP do not include naturally occurring pathogens that are circulating in or have been recovered from nature, regardless of their pandemic potential.