Gene Drives

Gene Drive Systems

Gene drive systems are capable of altering the traits of wild populations and associated ecosystems.

Natural forms of gene drive are found in just about every species.  They work in many different ways, but all can spread through populations even though they don't help organisms reproduce. Most achieve this by copying themselves or otherwise ensuring that they're more likely to be inherited than a typical gene.  The discovery of CRISPR, a powerful genome editing tool, allows scientists to build gene drive systems capable of editing almost any gene in sexually reproducing species.

Self-propagating drive systems are likely to spread to every population of the target species in the world.

Local drive systems are confined to regional populations. Daisy drive systems are an example of a powerful but local form of drive.

Key Resources
- A detailed gene drive FAQ focused on CRISPR-based self-propagating drive systems
- A comprehensive analysis of safeguards for gene drive research
- All current gene drive research projects and collaborations involving the Sculpting Evolution Group
- An explanatory guide to daisy drive systems, which are CRISPR-based but will alter only local populations.

In a landmark paper published in 2003, Austin Burt of Imperial College London first proposed that gene drives based on homing endonucleases might be used to alter or suppress wild populations. But the endonucleases available at the time couldn't be used to drive useful alterations through most species or in a way that was evolutionarily stable.

In July 2014, we publicly outlined a technically feasible way to use CRISPR/Cas9, a genome editing technology we co-developed, to drive almost any genome alteration through sexually reproducing populations. These "RNA-guided gene drives" or "CRISPR-based gene drives" could let us spread most traits we know how to alter with CRISPR. Given enough generations, nearly all organisms of the target population would have the same changes as those originally generated in the laboratory. Drive systems have now been demonstrated in yeast, flies, and two species of malarial mosquitoes.

Gene drives could benefit human health by altering insect populations that currently spread diseases such as malaria, schistosomiasis, dengue, and Lyme so that they can no longer transmit the disease to humans.  They could improve the sustainability of agriculture by reducing the need for and toxicity of pesticides and herbicides.  Finally, they could aid ecological restoration by removing invasive species and bolstering the defenses of threatened organisms. Collectively, they offer a way to solve biological problems with biology instead of broadly toxic pesticides and bulldozers. On a metaphorical level, we are finally learning to speak with the living world using nature's own language.

But because gene drives alter the shared environment, they must never be deployed without the support of the people. Even developing a CRISPR gene drive in the laboratory is ethically questionable because an accident could directly impact the lives of others, not to mention seriously damage public trust in scientists. Any scientists interested in working with gene drives should commit to using appropriate safeguards and making all proposals and results openly available from the start of the project.  Our own projects and collaborations are detailed here.

We recently reported a local CRISPR-based drive system that we devised: the daisy drive.  Daisy drives can mimic the activity of any global CRISPR-based drive system, but cannot spread indefinitely because they are constructed in the form of a daisy-chain that successively loses elements over generations.  Once a daisy drive system runs out of elements, it can no longer spread.

In contrast, we find that self-propagating gene drive systems are highly invasive. Those that alter populations are likely to spread to most or all populations connected by gene flow. Even highly inefficient drive systems that are rapidly outcompeted by resistant alleles still require only a handful of introduced organisms to invade a new population, and will reliably spread to other populations before being outcompeted.

- Our original manuscript in eLife is still the most comprehensive description of RNA-guided gene drives. It details ways of building evolutionarily stable drive systems, methods of overwriting changes if something goes wrong, confinement strategies to safely perform experiments, and diverse applications. We chose to defy tradition by publicly describing the technology and its potential before performing experiments in the laboratory in the hope of setting an example for future research in the field.

- Our paper in Science analyzes potential concerns and recommends safeguards and regulatory changes.
- Our paper in Nature Biotechnology (bioRxiv preprint) examines safeguards, efficacy, and reversal in yeast.
- A history of gene drives by Fred Gould.
- An excellent book on gene drives and "selfish" genetic elements by Austin Burt and Robert Trivers.
- A study that used an RNA-guided Cas9 gene drive to make fruit flies with mutations in both copies of a gene.
- A manuscript describing a candidate drive system to spread malaria resistance through populations of a minor mosquito vector.
- An beautiful effort to build population suppression drive systems in the primary mosquito vector of malaria.
- Our preprint on daisy drive systems (also on bioRxiv).
- Our preprint on the invasiveness of self-propagating alteration drive systems.

Selected Popular Media
- Our guest blog post at Scientific American focuses on capabilities and ethical considerations.
- An article written by Kevin for Project Syndicate on responsible paths forward.
- The original Wyss Institute press release.
- NOVA has a well-written optimistic take on gene drives.
- For a more conservative view, see the article at the Boston Globe.
- National Geographic focuses on the potential to improve the environment by controlling invasive species.
- The New York Times discusses the potential to control or eradicate malaria.

Gene Drive-HD.mp4

Video by Lei Jin and Seth Kroll of the Wyss Institute based on a transcript we wrote.