Gene drives can be controlled, new modeling suggests

By Joan Conrow

April 4, 2019

New scientific modeling suggests that gene drive technology can be controlled and kept from spreading unchecked when released into the environment.

The research, published this week in the Proceedings of the National Academy of Sciences (PNAS) Journal, addresses a key concern with a technology that is seen to offer hope for controlling invasive species and insects that carry deadly diseases like malaria — without the use of insecticides, rodenticides and other poisoning agents.

“CRISPR-based gene drive systems—genetic elements which could be engineered to rapidly spread traits through wild populations—could help solve some of humanity’s greatest ecological and public health problems,” the authors write. “However, if released, current versions might spread through a nontarget population—possibly across political borders—greatly complicating decision-making.”

In response, the researchers developed mathematical models that suggest self-limiting “daisy-chain” gene drives will not spread indefinitely. They also identified various CRISPR sequences that could enhance the stability of these daisy-chain systems.

“Imagine you have a chain of daisies, and at each generation you remove the one on the end. When you run out, the daisy chain drive stops,” explains Kevin Esvelt, the assistant professor of media arts and sciences and head of the Sculpting Evolution research group at the Massachusetts Institute of Technology Media Lab who co-led the research.

Though daisy-drive organisms function like other gene drives, in terms of self-propagation, the successive loss of nondriving genetic elements from one end of the chain limits their ability to spread indefinitely, the authors explain. By using molecular constraints to limit generational and geographic spread, their functions can be more carefully targeted.

“We’re programming the organism to do CRISPR genome editing on its own, within its reproductive cells, in each generation,” Esvelt says.

Gene drive technology has been moving forward in a bid to halt vector-borne diseases like Lyme disease, malaria and Zika; control rodent populations that are destroying endangered birds in island ecosystems, and to support sustainable agriculture. But critics have expressed reservations that gene drives could be impossible to control, resulting in unintended consequences once released into the environment.

In response, scientists have been looking at ways to essentially add a “stop” function to the technology. The PNAS paper, written by researchers at Harvard University and the Massachusetts Institute of Technology, suggests that daisy chain gene drives could accomplish that goal.

“If the world is to benefit from new gene-drive technologies, we need to be very confident that we can reverse it and contain it, both theoretically and via controlled tests,” says George Church, a professor of genetics at Harvard Medical School who helped develop the modeling system.

Use of daisy chain drives could also help resolve ethical concerns about how and where the gene drive technology should be used.

“Technologies capable of unilaterally altering the shared environment require broad public support,” the researchers write. “Because people will not be able to opt out of technologies intended to alter the shared environment, ethical gene-drive research and development should be openly guided by the communities and nations that depend on the potentially affected ecosystems. A method of preventing gene-drive systems from spreading indefinitely would greatly simplify community-directed development and deployment, while also enabling safe field testing.”

The authors caution that additional feasibility studies should be conducted to ensure that daisy-drive systems are powerful enough to eliminate all copies of an unwanted self-propagating drive system as a means to control accidental or unauthorized releases.