A framework for captive trials of genetic biocontrol technologies for invasive rodents

Genetic biocontrol technologies, including synthetic gene drive, offer promising alternatives to conventional approaches for managing invasive rodent populations that threaten biodiversity, agriculture, and human health. Recent advances, most notably the development of tCRISPR as the world’s first functional mammalian gene drive proof‑of‑concept, have accelerated progress toward potential applications. The responsible translation of laboratory proof‑of‑concepts to practical application requires rigorous testing under contained conditions. Caged or pen‑based trials are a critical component of phased gene drive development pathways, enabling evaluation of efficacy and safety prior to any consideration of environmental release. Existing guidance for such trials has been developed exclusively for insect systems and does not adequately address the biological, logistical, and ethical challenges associated with vertebrates. Rodents differ fundamentally from insects in reproductive biology and behaviour, social structure, population density dependence, generation time, and spatial ecology. In addition, vertebrate research is subject to stringent institutional animal ethics requirements that constrain enclosure design, population density, enrichment, and trial duration. Together, these factors have major implications for trial scale, inference, and risk management. Here, we present a conceptual framework for the design and implementation of captive trials of genetic biocontrol technologies in invasive rodents. Using the development of tCRISPR in Australia as a case study, and drawing on recent empirical and modelling studies, we outline a phased, modelling‑informed approach that balances scientific rigor, animal welfare, and biosecurity.