Biologists create new genetic systems to neutralize gene drives

UC San Diego scientists and their collaborators have developed two new genetic systems that inhibit or eliminate gene drives after release. Sincerely: Ana Silva

Over the past decade, researchers have designed an array of new tools that control the balance of genetic inheritance. Based on the CRISPR technique, such gene drives are induced to be transported from the laboratory to the forest, where they are engineered to suppress devastating diseases such as mosquito-borne malaria, dengue, zika, chikungunya, yellow fever and the West Nile . Gene drives carry the power to immunize mosquitoes against malaria parasites, or act as genetic pesticides that reduce mosquito populations.

Although the latest gene drives have been proven to spread efficiently designed in laboratory settings, concerns have been raised about the safety of releasing such systems into wild aggregates. Questions have emerged about the predictability and controllability of gene drives and whether, once loose, they can be called back into the field if they extend beyond their intended application area.

Now, University of California scientists San Diego and their partners have developed two new active genetic systems that address such risks by preventing or eliminating gene drives in the wild. In Journal on September18, 2020 Molecular cellThe research, led by Jiang-Ru Xu, Emily Bulger and Valentino Gantz in the Department of Biological Sciences, provided two new solutions based on the elements developed in the mango fruit fly.

Distinguished Professor Ethan Biere, senior author and science director of the paper, Tata Institute for Genetics and Society, said, “One way to reduce the perceived risks of gene drives is to stop their spread or, if necessary, remove them.” ” “There is a lot of concern that there are a lot of unknowns associated with gene drives. We have now saturated the possibilities at both the genetic and molecular levels, and are reducing the evolved elements.”

Biologists create new genetic systems to neutralize gene drives

Working at the genetic and molecular levels, UC San Diego scientists have developed two new genetic control systems to prevent or eliminate gene drives after release. Sincerely: Ana Silva

The first neutralizing system, called E-CHCR (erasing hitchhiking on autocatalytic chain reaction), is designed to prevent the spread of gene drives “by shooting with your gun”. e-CHACRs use the CRISPR enzyme Cas9 carried on a gene drive to self-copy, while simultaneously mutating and inactivating the Cas9 gene. Xu states that E-CHCR can be placed anywhere in the genome.

“Without the source of Cas9, it is inherited like any other common gene,” Xu said. “However, once an e-CHACR encounters a gene drive, it deactivates the gene drive in its tracks and continues to propagate for several generations chasing the drive element until its function is lost from the population. go.”

A second neutralizing system, called ERACR (Element Elementing Elemental Chain Reaction), is designed to completely eliminate gene drive. ERACRs are inserted in place of gene drives, where they use Cas9 from gene drives to attack from either side of Cas9. Once the gene drive is removed, the ERACR copies itself and replaces the gene-drive.

“If the ERACR is given an edge by carrying a functional copy of the gene that is interrupted by the gene drive, it runs across the finish line, completely eliminating the gene drive, which has an unfinancing resolution. ”

Biologists create new genetic systems to neutralize gene drives

E-CHACRs and ERACRs are powerful new gene drive control mechanisms. Credit: Emily Bulger and Ana Silva

The researchers rigorously tested and analyzed the resulting DNA sequences in careful detail at the molecular level, as well as the E-CHACRs and ERACRs. Beer estimates that the research team, which includes UC Berkeley’s mathematical models, spent an estimated 15 years of effort extensively developing and analyzing new systems. Nevertheless, he cautioned that there are unpredictable scenarios that may emerge, and neutral systems for field-acting gene drives should not be used with false protection.

He said, “Such breaking elements must now be developed and kept in reserve, because it is not needed because it is not known that some of the seemingly extraordinary interactions between these elements and the gene drive are designed for unethical activities. Are, “he said.

According to Bulger, gene drives have a lot of potential to reduce misery, but deploying them responsibly depends on control systems, which can lead to unexpected results. ERACRs and eCHACRs provide ways to prevent gene drives from spreading and, in the case of ERACRs, can potentially revert an engineered DNA sequence to a state very close to a naturally occurring sequence.

“Because ERACRs and e-CHACRs do not have their own source of Cas9, they will only spread as gene drives and not edit wild-type populations,” Bulger said. “These technologies are not perfect, but we now have a more comprehensive understanding of why and how unintended consequences affect their function and we believe they have the potential to be powerful gene drive control mechanisms that must arise . ”

Better CRISPR gene drive solves old technology problems

more information:
Molecular cell (2020). DOI: 10.1016 / j.molcel.2020.09.003

Provided by University of California – San Diego

Quotes: New genetic to neutralize biologist Gene Drive (2020, 1 retrie September, 18 September) on 10 September 2010 from System.

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