Rodent gene drives for conservation: opportunities and data needs

Abstract

Invasive rodents impact biodiversity, human health and food security worldwide. The biodiversity impacts are particularly significant on islands, which are the primary sites of vertebrate extinctions and where we are reaching the limits of current control technologies. Gene drives may represent an effective approach to this challenge, but knowledge gaps remain in a number of areas. This paper is focused on what is currently known about natural and developing synthetic gene drive systems in mice, some key areas where key knowledge gaps exist, findings in a variety of disciplines relevant to those gaps and a brief consideration of how engagement at the regulatory, stakeholder and community levels can accompany and contribute to this effort. Our primary species focus is the house mouse, Mus musculus , as a genetic model system that is also an important invasive pest. Our primary application focus is the development of gene drive systems intended to reduce reproduction and potentially eliminate invasive rodents from islands. Gene drive technologies in rodents have the potential to produce significant benefits for biodiversity conservation, human health and food security. A broad-based, multidisciplinary approach is necessary to assess this potential in a transparent, effective and responsible manner.

Gene drive: progress and prospects

“…R. Soc. B 286: 20192709 also been proposed as an effective and humane means to regulate invasive species, for example, rodents on islands [36] (see also Godwin et al [15]; Manser et al [17] in this issue). The potential benefits are impressive: a reduced risk of insect-transmitted disease and reduced reliance on pesticides with all the associated detrimental side effects (such as bioaccumulation in human food [37] or non-target wildlife poisoning [38]).…”

Split drive killer-rescue provides a novel threshold-dependent gene drive

“…Examples of how this could be arranged include the proposed X-shredder system 43,44 in Anopheles mosquitoes (vectors of malaria) in which sgRNA(s) direct an endonuclease to cleave repeated sequences on the X chromosome, producing a male sex bias; disruption/ectopic expression of the transformer 45 or Maleness-on-the-Y genes 46 , respectively, in the Mediterranean fruitfly Ceratitis capitata or ectopic expression of the nix and myo-sex genes in Aedes aegypti 47 . Due to the relative ease with which they can be manipulated genetically, examples are predominantly insect-related however, similar situations exist for the control of invasive vertebrates, for example the incorporation of the Sry gene [48][49][50][51][52] in house mice, or aromatase inhibitor constructs in invasive carp 51 , both of which could convert females into males. At present for mice, females converted into males are functionally sterile [48][49][50] , however future work may be able to overcome this issue.…”

Whose intentions? What consequences? Interrogating “Intended Consequences” for conservation with environmental biotechnology

“…The GBIRd, an international consortium of scientists and partners including the NGO Island Conservation, is trying to develop a gene drive mouse to eradicate invasive rodents on islands. Research is underway to construct a gene drive for mice that would bias offspring to be all male, which would crash an island population over several generations (Barnhill‐Dilling & Delborne, 2019; Godwin et al, 2019; Leitschuh et al, 2018).…”