New research shows promising potential in using genetic engineering tools to eliminate the spread of mosquito-borne diseases. By altering mosquito genes involved in the transmission of disease and spreading genetic changes across the entire population, the ability of mosquitoes to transmit diseases like malaria, zika, dengue, and yellow fever can be eliminated.
This new genetic tool is called gene drive. If used correctly, it can bypass the natural process of evolution, allowing selected genes to be passed down and rapidly spread throughout the population. By introducing one gene drive mosquito that is unable to transmit malaria into the wild, the entire mosquito population would soon lose the ability to transmit malaria.
Introduction to Gene Drive for Malaria
Gene drive uses the bacterial derived gene-editing system called CRISPR to insert, remove or alter genes. Inserting the system itself into an animal will allow it to edit its own genome. In classical genetics, the offspring receives one set of genes from the mother and the other set from the father. If the father has a unique gene, only about 12% of the progeny will have this gene after two generations. In a gene drive model, if the father has a gene drive, it will genetically edit the mother’s copy, giving the animal two sets of the father’s gene. Within two generations, 100% of the progeny will possess this gene. For malaria, the idea is to introduce a gene drive that would render the target mosquito and later, its progeny, unable to transmit the disease to humans.
Adapted from Nature.com
An Important First Step: The First Genetically Modified Mosquitoes Released into the Wild
Research published in 2011 from the Imperial College London established the foundations for this technology. In a controlled lab environment, the researchers showed that a gene inserted into a mosquito spreads to more than 85% of the mosquito progeny after 10 generations. Over the past eight years, researchers have made major improvements in optimizing the gene drive mechanism in mosquitoes.
Most recently, on July 1, 2019, a test batch of 10,000 genetically engineered mosquitoes was released into Burkina Faso. These mosquitoes are not equipped with gene drive but it is the first time genetically modified mosquitoes have been released into the wild. This test will provide scientists with important information about the effects of releasing genetically modified animals into the wild. The next step will be to improve this technology to be able to release gene drive mosquitoes into the wild to eliminate the spread of malaria.
The Challenges of Gene Drive
The big question is how can we test and regulate this technology? Conceptually, gene drive is an effective way to engineer the genome to eliminate insect-borne diseases, control invasive species, and reduce or eradicate genetic diseases in humans. A technical problem in this research is that there is a higher accumulation of mutations within the inserted CRISPR system. This may inactivate the system, potentially giving the animal resistance or causing other unknown changes in the animal. These unknown changes could have devastating effects on the ecosystem.
Gene Drive in Mammals
So far there have only been promising results in mosquitoes and fruit flies. In mice, this technology is far from being practical. In 2019, a group showed some success in a mouse model but had seen difficulty in propagating these genes across multiple generations. Getting this to work efficiently in mice will be difficult but will lead the way in potentially using it in humans.
Final Thoughts
There is still much to learn on the basic mechanisms behind gene drive technology. We do not fully understand the effects of inserting gene editing tools into organisms, let alone organisms in a wild ecosystem. The potential upside of this technology can be revolutionary but if gone awry, it could be catastrophic. Researchers hope to continue to optimize this system to better understand how it can work reliably in animals. Hopefully, we will soon be able to use gene drive technology to eliminate mosquito-borne diseases and in the far future, use it to cure many diseases in humans.
Further Resources:
Here is a fun video about how gene drives are being used to fight malaria:
Here is an informative article on gene drive:
References
Windbichler, N. et al. Nature 473, 212–215 (2011). PubMed, Article, Google Scholar
Kyrou, K. et al. Nature Biotechnol. 36, 1062–1066 (2018). PubMed, Article , Google Scholar
Grunwald, H. A. et al. Nature 566, 105–109 (2019). PubMed, Article, Google Scholar
Noble, C. et al. Proc. Natl Acad. Sci. USA 116, 8275–8282 (2019). PubMed, Article, Google Scholar
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