Recently developed CRISPR–Cas9-based gene-drive systems are highly efficient in laboratory settings, offering the potential to reduce the prevalence of vector-borne diseases, crop pests and non-native invasive species.
However, concerns have been raised regarding the potential unintended impacts of gene-drive systems.
This Review summarizes the phenomenal progress in this field, focusing on optimal design features for full-drive elements (drives with linked Cas9 and guide RNA components) that either suppress target mosquito populations or modify them to prevent pathogen transmission, allelic drives for updating genetic elements, mitigating strategies including trans-complementing split-drives and genetic neutralizing elements, and the adaptation of drive technology to other organisms.
These scientific advances, combined with ethical and social considerations, will facilitate the transparent and responsible advancement of these technologies towards field implementation.
Since getting on the road, gene-drives have sped a long way. New high-performance vehicles offer great promise for delivering anti-malarial effectors or driving down the numbers of mosquitoes. Flexible add-on trailers (for example, CHACRs) could also update or expand the range of the original drives and, should a drive go errant, strategies for forcing them to pull-over (e-CHACRs) or exit (ERACRs) are now available. Such technologies should be portable to other insects and, with further development, perhaps transferred to other organisms, including vertebrates, plants and even bacteria. So, what is next?
Beyond the several technical and ethical challenges described in this Review and elsewhere, I would like to highlight two main challenges facing the gene-drive field.
The first is to obtain both regulatory and community approval to test these systems in natural confined environments such as isolated islands (phase 2 trials) or other controlled contexts.
These trials are essential for obtaining data to evaluate the future potential of candidate drive systems. There is no other way to know how drives will perform in nature under conditions where they must compete with native mosquitoes, which may be much more extreme than in the laboratory. Approval for such phase 2 trials may take time and will depend greatly on efforts such as those already well under way to engage local communities in an open and transparent fashion regarding scientific and ethical issues163,166.
The second challenge, which in many ways rests on the results of the first, is to delineate when and where such drives could be released in phase 3 efforts to reduce disease prevalence. Each drive system will need to develop a detailed target–product profile, which should be evaluated on a case-by-case basis. It will also be important to consider how new drive systems might interact with those already in the environment to avoid potential clashes analogous to those arising from space junk.
In summary, so far, it has been a remarkable drive, through an incredible landscape. The big question is what lies on the road ahead and will the promise of gene-drives deliver the potential they seem to hold?
Ethan Bier is a professor in the section of Cell and Developmental Biology at UC San Diego. He has been engaged in analysis of developmental pathways that establish the primary axes of the fruit fly embryo and larva in Drosophila.
A version of this article was originally posted at Nature Reviews Genetics and is reposted here with permission. Nature can be found on Twitter @Nature
