GainofFunction

Gain-of-function (GOF) refers to genetic modifications or mutations that confer new or enhanced properties on a biological system. In genetics, GOF mutations may create novel enzyme activities, broaden substrate specificity, or increase expression. In virology and microbiology, GOF commonly denotes experiments that enhance a pathogen’s properties, such as replication efficiency, host range (the species it can infect), transmissibility, virulence, or the ability to evade immune responses. Such research aims to understand disease mechanisms, predict potential threats, and improve surveillance, therapeutics, or vaccines. However, GOF experiments also pose biosafety and biosecurity concerns because they could potentially create more dangerous agents if modified organisms are released or misused.

Regulatory and ethical context: GOF research is subject to dual-use considerations and DURC (dual-use research of concern) frameworks. Several countries have implemented oversight policies, guidelines, and funding controls to assess risk-benefit and ensure appropriate containment, risk assessment, and incident reporting. In the United States, controversial GOF studies of highly transmissible avian influenza viruses prompted funding pauses and the development of oversight frameworks; many institutions require institutional biosafety committee reviews and adherence to biosafety level practices and incident reporting. Internationally, there are ongoing debates about how best to balance scientific openness with safety, and about the level of risk deemed acceptable for such experiments.

Limitations and alternatives: GOF concepts also apply to non-pathogenic organisms and molecular biology, where researchers study the function of genes or proteins without enhancing properties that pose risks. Some scientists advocate for alternative approaches, such as computational modeling or non-pathogenic surrogates, to address core questions without creating risky agents.