Key findings

• Gene drives have been developed in at least five mosquito species and are proposed in several more. These include species like Anopheles gambiae, the African malaria mosquito, and species from other mosquito groups (genera) which don’t transmit malaria, such as Aedes aegypti, also known as the yellow fever mosquito.[ 3.2 ]
• Gene drives are under active development in other insect species, such as the fruit flies Drosophila suzukii and Ceratitis capitata and the diamond back moth, Plutella xylostella. Beyond the organisms where gene drives are under active development, more than 30 other insect species have been proposed as targets, from orders including the diptera (true flies), lepidoptera (moths and butterflies), coleoptera (beetles), hemiptera (true bugs) and hymenoptera (ants, wasps, bees and sawflies), with preliminary work such as genome sequencing undertaken in some cases.[ 3.3 ]
• There are proposals to develop gene drive technology in several mammals including the European rabbit, feral cats, European foxes, various species of rats, and mice. Research on gene drive construction has so far mostly been limited to work on mice, which are seen as a providing a pathway to develop the technology in other mammals. While this intention is often stated in general terms, an example that names a specific eventual target is the study from Castle et al. (2022) who use mice as a model organism with the ultimate aim of modifying deer.[ 3.4 ]
• Other vertebrates have also been proposed as targets, for example the European Carp, the sea lamprey and the European starling. Research may be underway towards constructing gene drives in the European carp.
• There is a significant body of research on gene drives in various species of fungi and some engineered gene drive systems in fungi have been demonstrated in the lab [ 3.5 ]. Whilst the vast majority of this research has been in model organisms where there is no intention to release, there has also been research aiming to target certain wild species of fungi that cause crop disease. The feasibility of such proposals remains unclear.
• As highlighted above, gene drive systems have now been developed in the model plant Arabidopsis thaliana.  At least 15 species of plants considered as weeds or invasive species have been identified as gene drive targets in the literature to date.
• There have been projects or proposals to develop gene drives in other taxonomic groups including nematodes, flatworms, spider mites and snails. No functional gene drives have yet been described for any of these groups, though it appears efforts have been made in some cases, for example in the nematode  Caenorhabditis brenneri.

• In insects, gene drives are under development or have been proposed for 44 insect targets, the majority of which are agricultural pests, 24 in total. These also include five livestock pests or livestock disease vectors, some of which are also human disease vectors.[ 3.6 ]
• The crop pests ‘spotted wing drosophila’ (Drosophila suzukii), ‘medfly’ or Mediterranean fruit fly (Ceratitis capitata) and the ‘diamondback moth’ (Plutella xylostella) are the focus of significant gene drive development efforts. [ 3.7 ]

• Of the 44 insect targets where gene drives have been proposed, or are being developed, 16 are vectors of human disease in particular malaria.[ 3.8 ]
• While there is a large body of gene drive research targeting malaria vectors, there is substantial effort going towards developing gene drives in the mosquito species Aedes aegypti and Culex quinquefasciatus, which are not malaria vectors, but are vectors for other diseases. Aedes aegypti is a vector for Yellow fever and Dengue fever for example, while both species transmit Zika virus. [ 3.7 ]

• Only six insect species are proposed as targets because of their impacts on biodiversity as invasive species, in some cases these insects also have impacts on agriculture or act as vectors for human disease. One additional group is proposed as a target for forest management purposes.  [ 3.9 ]
• Prevention of biodiversity loss appears to be a more significant driver for gene drive development in vertebrates. 19 of the 20 vertebrate targets relate to controlling or eliminating invasive species for conservation and biodiversity purposes, especially mammals. [ 3.10 ] As described above significant efforts are being made to construct gene drives in mice, and some preliminary work has begun in other vertebrate targets such as genome sequencing. 

• At the present time no projects are close to producing a proven ‘product’. But some gene drives in mosquitos are closer to potential field trials, pending on regulation, reduced uncertainty, risk assessment and further technical developments. [ 3.11] Questions around recallability and reversibility also remain. Our infographic gives an overview of the most advanced gene drive development projects.
• Compared to gene drive systems in mosquitos and fruit flies, technological difficulties mean that systems in other taxonomic groups (e.g. mammals) are further away from potential releases in the environment. A significant amount of research has focussed on developing gene drives in mice, while there has been limited success with established homing CRISPR gene drive designs, efforts to construct new forms of gene drive in mice are ongoing.

• Many forms of gene drive technology have been proposed, however fewer have been constructed and tested in laboratories. A variety of gene drive systems have been constructed in laboratories, many in the model organism Drosophila melanogaster, a fruit fly, and some in other organisms such as the mosquito Anopheles gambiae. We do not currently include research in Drosophila melanogaster in our database because there is no intention to target wild populations.
• The majority of projects currently employ homing CRISPR gene drive technology, based on the DNA cutter CRISPR/Cas9. We include a brief description of this approach here.
• A variant of this technology known as split homing CRISPR gene drive has also emerged.  [ 3.12]

• Other forms of gene drive technology that have been validated to some extent in target species include:

(1) So called ‘Medea’ in Drosophila suzukii, a type of ‘toxin antidote’ gene drive system.

(2) Toxin antidote based gene drives have been developed in the plant, Arabidopsis thaliana (see here and here)

  (3) Gene drives are being developed in mice based on the T-haplotype, a natural occuring selfish genetic element.

(4) A gene drive system based on the natural selfish genetic element Spok1 has been constructed in the fungi Fusarium graminearum.

• As stated above, other forms of gene drive technology have been constructed and tested in the model organism, Drosophila melanogaster, but with no intention to release.
• Sex ratio distorter systems, known as ‘X-shredders’ have also reached a relatively advanced stage in development, and are included in our database due their similarities to gene drives [ 3.13 ].

• A so called ‘Y-shredder’ sex ratio distorter system has now been constructed in Anopheles gambiae. This works on similar principles to the X-shredder but generates a female bias.

• Homing CRISPR-based gene drives have been shown to function with moderate to high efficiency in a number of insect species in laboratory settings, which are all members of the order Diptera (true flies, which also includes mosquitoes). Within the Diptera efficient homing gene drives have been demonstrated within the mosquito genera Anopheles and Aedes, and in the fruit flies Drosophila melanogaster, Drosophila suzukii and Ceratitis capitata [add link]. It is notable that within another member of the Diptera, the mosquito Culex quinquefasciatus, a homing gene drive so far operates only at low efficiency.
• In insects outside of the Diptera there is only one example of a homing CRISPR based gene drive showing any level of functionality: a system constructed in the diamondback moth (Plutella xylostella) that only operates with very low efficiency. Prior to this, the research group involved took the unusual step of publishing results describing an unsuccessful attempt to construct a gene drive in this species. It is difficult to assess how many unsuccessful attempts have been made to construct such systems in other insects, as such results may well not be published.
• It remains uncertain how widely applicable homing CRISPR gene drive technology is across different species and taxonomic groups. While homing CRISPR gene drives appear to be functional in laboratory settings in some dipteran insects (i.e. certain flies and mosquitoes) and some fungi (S. cerevisiae and C. albicans) the technology is so far only partially functional in mice. Despite efforts to apply this technology more widely, it is not yet functional in plants, nematodes or in the fungi Fusarium graminearum.
• Gene drive designs not based on homing CRISPR technology may be more effective in some species. Development of designs based on the T-haplotype in mice and Spok1 in F. graminearum, appear to have made some progress in the laboratory, while in these species homing CRISPR gene drives are relatively, or completely, ineffective.  While several other forms of gene drive technology  have been developed and tested in dipteran insects [true flies] (such as underdominance, toxin-antidote systems and sex ratio distorter gene drives), these approaches have not been tested in other taxonomic groups.