Scientists Develop New Genetic Techniques to Stop Mosquitoes that Spread Malaria
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Malaria remains one of the deadliest diseases in the world. Every year, malaria infection causes hundreds of thousands of deaths, most of which occur in children under the age of five
Malaria remains one of the deadliest diseases in the world. Every year, malaria infection causes hundreds of thousands of deaths, most of which occur in children under the age of five. The Centers for Disease Control and Prevention recently announced that five mosquito borne malaria cases have been found in the United States (four in Florida and one in Texas), which is the first report of malaria transmission in the country in 20 years.
Fortunately, scientists are developing safety technologies to prevent the spread of malaria by genetically editing mosquitoes that transmit the parasites that cause the disease. The researchers in Professor Omar Akbari's laboratory at the University of California, San Diego, designed a new method that can genetically inhibit the population of Anopheles gambiae, which mainly transmits malaria in Africa and causes economic poverty in the affected areas. The new system targets and kills Gambian females as they bite humans and spread diseases.

Researchers at the University of California, San Diego have developed a new technology to suppress Anopheles gambiae, which mainly spreads malaria in Africa and leads to economic poverty in affected areas. Image source: Akbari Laboratory, University of California, San Diego
Andrea Smidler, the first author and a postdoctoral scholar of the School of Biological Sciences of the University of California, San Diego, and James Pai and Reema Apte, former master students and co first authors, published in the journal Progress in Science on July 5, creating a system called Ifegenia, the abbreviation of "hereditary female elimination of interrupted alleles through gene encoded Nuclease". This technology utilizes CRISPR technology to disrupt the femaless (fle) genes that control the sexual development of Gambian mosquitoes.
Scientists from the University of California, Berkeley and the California Institute of Technology contributed to this research.
The working principle of Ifegenia is to encode the two main components of CRISPR in African mosquitoes. These include Cas9 Nuclease, the molecular "scissors" for cutting, and the guiding RNA to guide the system to the target through the technology developed in Akbari laboratory in these mosquitoes. They genetically modified two mosquito families to express Cas9 and fle targeting guide RNA, respectively.

The artist's depiction of Ifegenia is a new technology developed by the University of California, San Diego, which uses CRISPR gene editing to disrupt the genes that control the sexual development of African mosquito larvae. Image source: ReemaApte
We hybridized them and in their offspring, all female mosquitoes disappeared, "Smidler said." This is really extraordinary. "At the same time, Gambian male mosquitoes inherited Ifegenia, but genetic editing did not affect their reproduction. They still have the ability to reproduce and can mate and spread Ifegenia. Due to the removal of females and the population reaching a breeding dead end, this insect borne transmission was ultimately stopped. The author points out that the new system avoids some genetic resistance obstacles and control problems faced by other systems such as Gene drive, because Cas9 and the guiding RNA component remain separate until the population is ready to be suppressed.
In the paper, the author points out: "We demonstrate that Ifegenia males still have reproductive ability and can load fle mutations and CRISPR mechanisms to induce fle mutations in offspring, leading to sustained population suppression. Through modeling, we demonstrate that repeatedly releasing non biting Ifegenia males can serve as an effective, restrictable, controllable, and safe population suppression and eradication system

In the new population suppression system, Anopheles gambiae larvae were injected with CRISPR based gene editing tools. Image source: Akbari Laboratory, University of California, San Diego
More and more facts have proven that traditional methods such as mosquito nets and insecticides to combat the spread of malaria are ineffective in preventing the spread of the disease. Pesticides are still widely used globally, mainly to prevent malaria, which increases health and ecological risks in Africa and Asia.
Before joining the University of California, San Diego in 2019, Smidler obtained a PhD in Public Health Biosciences from Harvard University and is applying her expertise in genetic technology development to address the spread of diseases and their economic hazards. When she and her colleagues developed Ifegenia, she was surprised by the effectiveness of this technology as a suppression system.

Andrea Smidler (left), the first author of Ifegenia technology research, and ReemaApte, the co first author. Image source: Akbari Laboratory, University of California, San Diego
"This technology has the potential to become a safe, controllable and scalable solution that the world urgently needs to eliminate malaria once and for all," said Akbar, professor of the Department of Cell and Developmental biology. Now we need to shift our efforts and seek social acceptance, regulatory authorization, and funding opportunities to make the system undergo final testing to suppress the spread of wild malaria in mosquito populations. We are about to have a significant impact on the world, and we will not stop until we achieve this goal. "Researchers point out that the technology behind Ifegenia can be applied to other species that transmit deadly diseases, such as dengue fever (bone fracture fever), which is known to spread Chikungunya and Yellow fever viruses.
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