Mosquitoes that can carry malaria eliminated in laboratory experiments

This is the first time that experiments have succeeded in completely blocking the reproductive capacity of a complex organism in the laboratory using a molecular designer approach.

The technique, called gene drive, has been used to selectively target specific mosquito species. One gambiae responsible for malaria transmission in sub-Saharan Africa. There are approximately 3500 mosquito species worldwide, of which only 40 related species may carry malaria.

The hope is that mosquitoes carrying a genetic drive will be released in the future, which will spread female infertility within local populations of mosquitoes carrying malaria and will cause them to collapse. .

In 2016, there were approximately 216 million cases of malaria and approximately 445,000 deaths worldwide, mostly among children under five.

Principal Professor Andrea Crisanti of Imperial Life's Department of Life Sciences said, "The year 2016 was the first in two decades that malaria cases have not diminished the fight."

The results of the team, published today in Nature Biotechnology, represents the first time that the genetic drive has been able to completely suppress a population, overcoming the resistance problems that the previous approaches have faced.

Professor Crisanti added, "This discovery shows that gene research can give us hope in the fight against a disease that has been rife for centuries in mankind, and there is still much to be done, both in education and in working with people. affected countries to assess the feasibility of such an intervention.

"It will still take at least 5 to 10 years before we consider testing mosquitoes with the search for genes in nature, but we now have encouraging evidence that we are on the right track." "Malaria eradication by overcoming the barriers of logistics in resource-poor countries. "

The team targeted a gene in One gambiae called doubleex, which determines whether an individual mosquito develops as a man or as a woman.

The team has designed a gene training solution designed to selectively alter a region of the doubleex gene responsible for female development. Males carrying this modified gene showed no change and females did not have a single copy of the modified gene. However, females with two copies of the modified gene had both male and female characteristics, did not bite, and did not spawn.

Their experiments showed that the gene mechanism transmits genetic modification almost 100% of the time. After eight generations no female was produced and the populations collapsed due to lack of offspring.

Previous attempts to develop gene search for population suppression have met with "resistance", where targeted genes have developed mutations that have allowed the gene to perform its function, but which were impulse-resistant. These changes would then be passed on to the offspring, putting an end to the search for genes.

One of the reasons why Doubleex was chosen for the gene search target was that it was thought that it did not tolerate any mutation, thus overcoming this potential source of resistance. Indeed, in the study, no mutated functional copy of the doubleex gene has occurred and has spread in the population.

Although this is the first time that resistance has been overcome, the team said additional experiments were needed to investigate the efficacy and stability of the genetic drive in confined laboratory environments mimicking tropical environments .

This involves testing the technology on larger mosquito populations confined to more realistic environments, where competition for food and other ecological factors can change the fate of the genetic drive.

The doubleex gene targeted in the study is similar in the insect world, although different insects have different exact genetic sequences. This suggests that the technology could be used in the future to specifically target other disease-carrying insects.

Recent work by Imperial Oil has shown that the deletion One gambiae populations in local areas are unlikely to affect the local ecosystem.

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More information:
Kyros Kyrou et al. A doubleex-targeted CRISPR-Cas9 gene drive causes complete suppression of the population in caged Anopheles gambiae mosquitoes, Nature Biotechnology (2018). DOI: 10.1038 / nbt.4245