The $ 3.9 million gene self-deletion venture targets mosquito-borne illnesses

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To control mosquito populations and prevent them from transmitting diseases such as malaria, many researchers are pursuing strategies in mosquito genetic engineering. A new Texas A&M AgriLife research project aims to provide temporary “test runs” of the proposed genetic changes in mosquitoes, which will remove the changes from the mosquito’s genetic code.

The first results of the project were published on December 28th in Philosophical Transactions of the Royal Society B entitled “Making Gene Drive Biodegradable”.

Zach Adelman, Ph.D., and Kevin Myles, Ph.D., both professors at Texas A&M College of Agriculture and Life Sciences, Department of Entomology, are the lead investigators. Over a five-year period, the team will receive USD 3.9 million in funding from the National Institute for Allergy and Infectious Diseases to test and optimize the self-extinguishing genetic engineering.

“People are wary of transgenes spreading uncontrollably in the environment. We believe our strategy is a strategy to potentially prevent this from happening,” Adelman said. “The idea is, can we program a transgene to remove itself? Then the gene won’t persist in the environment.

“It really comes down to how you test a gene drive in a real-world scenario.” he added. “What if a problem occurs? We believe our path is a way to conduct risk assessments and field tests.”

A crucial goal for mosquito control

Many genetic engineering proposals revolve around inserting a selected set of new genes into mosquitoes along with a “gene drive”. A gene drive is a genetic component that forces the new genes to spread across the population.

“A number of high-profile publications have talked about using a gene drive to control mosquitoes, either to modify them so they can no longer transmit malaria parasites or to kill all women and die the population,” Adelman said.

A concern that is often expressed is that such genetic changes could have unintended or harmful consequences.

A plan makes the cut

In the first publication of the project, the colleagues describe three ways in which an introduced genetic change can remove itself after a certain period of time. For example, the period could be 20 generations of mosquitoes, or about a year. The team used the generation times and parameters of the average life of a mosquito to model how the genes would spread among mosquitoes. Of the three methods, the team selected one to pursue further.

This method uses a process that all animals use to repair damaged DNA, Adelman said. Inside cell nuclei, repair enzymes look for repeated genetic sequences around broken strands of DNA. The repair enzymes then clear what’s in between repetitions, he said.

The Adelman and Myles team are therefore planning to test a fruit drive, a DNA-cutting enzyme, and a small replica of the insect’s DNA on fruit flies and mosquitoes.

Once the introduced enzyme cuts the DNA, the insect’s repair tools should go into action. The repair tools cut out the genes for gene drive and the other added sequences. At least that should happen in theory.

Failure is not just an option, it’s part of the plan

The team has already started laboratory work to test different gene drives and determine how long they last on flies and mosquitoes. The aim is for a gene drive to spread quickly in a laboratory insect population. After a few generations, the added genes should disappear and the population should again consist of wild-type individuals.

“We assigned different failure rates to determine how often the mechanism did not work as expected,” Adelman said. “The models predict that even with a very high failure rate, if it only succeeds 5% of the time, it will still be enough to get rid of the transgene.”

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