Toward translation of the world’s first murine gene drive: from laboratory proof-of-concept to island deployment

Invasive rodents have notoriously devastating impacts on island ecosystems, where conventional methods of control are often costly, can harm off-target species, and may sometimes fail to eradicate problem populations. Genetic biocontrols, wherein pest animal genomes are manipulated to impact normal reproduction, offer potential alternatives that are species-specific, and in the case of gene drive, highly efficient due to mechanisms that cause biased inheritance of the drive elements. Demonstration of the first mammalian proof-of-concept gene drive (tCRISPR), which leverages a natural meiotic drive in house mice (t-haplotype), represents a key empirical breakthrough. However, there is a critical need for ecological, behavioural, and population genetic research to progress this technology from the laboratory to a field-ready tool. Here we discuss a framework for effective translation of this technology, and present recent experimental progress using controlled crosses to transfer the tCRISPR construct for laboratory lines into a wild house mouse background, evaluate competitive ability of drive-bearing mice using mating trials, and validate biased transmission of the construct. We discuss essential next steps in this research program, including plans for the first caged trials of the tCRISPR mechanism.