In this animation, learn how effective safeguarding mechanisms developed at the Wyss Institute and Harvard Medical School can be applied to ensure gene drive research is done responsibly in the laboratory. These safeguards enable responsible scientific investigation into how gene drives could one day be leveraged for the greater good of human health, agriculture, and the environment.
In a given sexual reproduction cycle for any organism, each copy of a gene has a 50 percent chance of being inherited by offspring. However, employment of gene drive mechanisms, which sidesteps the normal inheritance rules, dramatically increases the odds that the gene drive will be passed along to the offspring. Put another way, gene drives are biased inheritance mechanisms that can quickly alter entire populations of organisms. Exploiting this mechanism for controlling populations of disease-carrying organisms or invasive plant and animal species is currently being reviewed for study by a number of research organizations.
Since the use of these synthetic biology mechanisms could have rapid, negative consequences for various organismal populations and ecological biodiversity, many within the scientific community and the general population have rightly expressed concern over the deployment of this technology. Now, in parallel with their development of the first synthetic gene drives, Harvard researchers George Church, Ph.D., and Kevin Esvelt, Ph.D., helped pioneer proactive biosafety measures to ensure that gene drives using the CRISPR-Cas9 genome editing technique are investigated effectively and safely in confined laboratory experiments. Published in a new study, the Harvard team demonstrated effective safeguarding mechanisms for working with gene drives and unveiled a novel method for reversing the changes they spread.
“Any claim of reversibility of modern technology requires strong evidence,” explained Dr. Church, who is a Wyss Institute for Biologically Inspired Engineering core faculty member, professor of Genetics at Harvard Medical School (HMS), and professor of health sciences and technology at Harvard and MIT. “This is a major step in that direction for the field of synthetic biology.”
The findings from this study were published recently in Nature Biotechnology through an article entitled “Safeguarding CRISPR-Cas9 gene drives in yeast.”
The current study verified the efficacy of safeguarding protocols developed by the Harvard investigators, such as increased and improved physical biocontainment barriers and the introduction of molecular confinement mechanisms, which use genetic engineering to block laboratory organisms from surviving and reproducing, were they ever to escape into the ecosystem.
“The gene drive research community has been actively discussing what should be done to safeguard shared ecosystems, and now we have demonstrated that the proposed safeguards work extremely well and should, therefore, be used by every gene drive researcher in every relevant lab organism,” stated Dr. Esvelt, a technology development fellow at the Wyss Institute.
Since the use of CRISPR, gene drives work through sequences of RNA guiding the gene-cutting Cas9 protein to a specific target, the researchers engineered molecular mechanisms to prevent gene drives from functioning in the wild by separating the guide RNA and the Cas9 protein so that they are not encoded together in the same organism. Alternatively, by inserting an artificial sequence into the targeted gene, gene drives can only be activated within lab organisms.
“Using yeast in the lab, we also showed that a trait imposed on a population using a gene drive could be reversed,” noted co-first author James Dicarlo, a graduate research assistant at the Wyss Institute and HMS.
Although more research needs to be performed before gene drives could ever potentially be ready for use outside of confined laboratory experiments, this study provides researchers the tools to perform those experiments safely. Moreover, the reversibility mechanism that the Harvard scientists developed isn't just a backup plan in case a gene drive ever had an unexpected side-effect—the ability to impose or reverse gene drive effects could also one day prove useful for the management of potentially pathogenic organisms or eco-destructive species.
“Gene drive technology has great potential to solve global problems, such as malaria, for which we have no solutions today,” said Wyss Institute founding director Donald Ingber, M.D., Ph.D., who was not directly involved in the current study. “But the field needs to proactively develop safeguard mechanisms and reversibility capabilities to ensure the safety of this new technology and enable its enormous potential for doing good.”