Current and proposed insect targets for gene drive development

Summary of findings
Gene drives are under development or have been proposed for 41 insect targets from six different orders.[1,2]

• This has increased by nine insect targets since our previous survey in April 2022.
• While 15 of the proposed targets are vectors of human disease,[3] in particular malaria, the majority are agricultural pests,[4] 22 in total. These include five livestock pests or livestock disease vectors, which partially overlap with human disease vectors.
• There is substantial effort going towards developing gene drives in the mosquito genera Aedes and Culex, which are not vectors of malaria.
• The crop pests ‘spotted winged drosophila’ (Drosophila suzukii) and the ‘diamondback moth’ (Plutella xylostella) are also the focus of substantial gene drive development efforts.
• Only five species are proposed as targets because of wider biodiversity impacts or combined economic loss and biodiversity impacts,[5] as well as one for forest management purposes and one for conservation, the latter again overlapping with human disease vectors.[6]
• The majority of gene drive proposals are based on eradication/suppression approaches. Only a very few are projects that are aiming to modify characteristics of insects in the wild.
• At the present time no projects are close to producing a usable and proven ‘product’. But some are closer to potential field trials, pending on regulation, risk assessment and further (technical) developments.
• CRISPR-based homing gene drives have been shown to function with reasonable efficiency in several members of the order Diptera (true flies), especially within the mosquito genera Anopheles and Aedes, and within the genus Drosophila. However it is notable that within another member of the Diptera, the mosquito Culex quinquefasciatus, a homing gene drive so far operates only at very low efficiency.
• It remains unclear how applicable homing CRISPR/Cas gene drives will be in insects outside of the Diptera. In non-dipteran insects there is only one example of a such a gene drive showing any level of functionality: a very low efficiency system constructed in the diamondback moth (Plutella xylostella).

Contextualisation

The emergence of gene drive technology opens-up unprecedented prospects of modifying, suppressing, or even eliminating wild species to serve human purposes. The consequences of choosing to go down this path are very difficult to foresee, especially in the longer term. To help frame further discussion on this topic, we have updated our survey of gene drive development in insects, screening the scientific literature up until September 2023. The survey also includes development of so-called ‘x-shredders’, a sex ratio distortion system with close similarities to gene drive technology.
We do not cover issues regarding risks, difficulties in performing robust risk assessments, or the lack of proven methods to confine, halt or reverse engineered gene drives.

Our survey gives an overview of:

• What research has taken place or is ongoing.
• Which species and taxa are current or proposed targets for gene drive development, and which types of gene drives are being put forward.
• How far along developments have progressed and what the next stages of experimentation might be.

Footnotes:

1. The vast majority of the targets identified in the literature are single species or species complexes, however some early stage proposals relate to broader taxonomic groups, namely the Glossina genus (Testse flies - row 23), the Scolytinae subfamily (Bark beetles - row 32) and the order Thysanoptera (Thrips - row 41).
2. Many experimental gene drive systems are being developed and tested in the model organism Drosophila melanogaster. Because we are not aware of any plans to target this organism in the wild, a survey of work in this species is not included here.
3. All 12 mosquito species listed in rows 1.1-12, the flies in rows 22 and 23, and the bug Rhodnius prolixus in rows 28.1-28.2.
4. Targets impacting crops are detailed in rows 13-16, 19, 24-27, 29-31, 33-35, 38, 41; targets impacting livestock are listed in rows 17, 18, 20, 21 and 23.
5. Targets impacting wider biodiversity (and economics) are detailed in rows 36-41.
6. Proposed targets for forestry are bark beetles in row 32, and for conservation is the mosquito Culex quinquefasciatus in row 12, a vector for bird malaria as well as for human and animal diseases.