New Genetic Tech Developed to Combat Malaria-Transmitting Mosquitoes

Malaria continues to be one of the most lethal illnesses globally. Each year, malaria infections claim the lives of hundreds of thousands of individuals, with children under the age of five primarily affected. The Centers for Disease Control and Prevention (CDC) recently revealed the detection of five instances of mosquito-borne malaria in the United States, marking the first recorded transmission within the country in twenty years.

Excitingly, researchers are making strides in developing secure technologies to halt the transmission of malaria by genetically modifying mosquitoes that carry the disease-causing parasite. Led by Professor Omar Akbari, a team of scientists at the University of California San Diego has devised a novel approach to genetically suppress populations of Anopheles gambiae, the primary malaria-transmitting mosquitoes in Africa, which contribute to economic impoverishment in affected regions.

The newly developed system

The newly developed system focuses on eliminating female mosquitoes of the A. gambiae species since they are responsible for spreading the disease through their bites.

Published in the journal Science Advances on July 5, the study details the work of postdoctoral scholar Andrea Smidler, along with former master’s students James Pai and Reema Apte, who co-authored the paper. They created a system called Ifegenia, which stands for “inherited female elimination by genetically encoded nucleases to interrupt alleles.” By utilizing CRISPR technology, the researchers disrupted a gene called femaleless (fle) that governs sexual development in A. gambiae mosquitoes.

The research effort involved collaboration with scientists from UC Berkeley and the California Institute of Technology. Ifegenia functions by genetically incorporating the two key components of CRISPR into African mosquitoes. This includes a Cas9 nuclease, which acts as molecular “scissors” for making cuts, and a guide RNA that directs the system to the target location, utilizing a technique developed in Akbari’s laboratory. Researchers genetically modified two mosquito families to express Cas9 and the guide RNA targeting the fle gene separately.

Smidler remarked, “We bred them together, and in the offspring, all the female mosquitoes died—it was truly remarkable.” On the other hand, male A. gambiae mosquitoes inherit Ifegenia without experiencing any reproductive consequences. They retain their ability to mate and disseminate Ifegenia.

Overcoming Challenges and Achieving Reproductive Halt

The researchers highlight that their innovative system overcomes certain challenges related to genetic resistance and control encountered by other approaches like gene drives. Keeping the Cas9 and guide RNA components separate until the population is ready to be suppressed achieves this accomplishment, resulting in the ultimate halt of parasite transmission as the population reaches a reproductive impasse through the elimination of females.

According to the authors of the study, “We have demonstrated that Ifegenia males retain their reproductive capabilities and can carry both fle mutations and CRISPR machinery to induce fle mutations in subsequent generations, resulting in sustained suppression of the population.” They further explain that through modeling, they have shown that releasing non-biting Ifegenia males in iterative cycles can serve as an effective, confined, controllable, and safe system for population suppression and elimination.

Conventional methods

Conventional methods like bed nets and insecticides have proven increasingly ineffective in combating the spread of malaria. Despite their extensive use, particularly in African and Asian regions, to curb malaria transmission, they pose health and ecological risks.

Smidler, who obtained her Ph.D. in biological sciences of public health from Harvard University before joining UC San Diego in 2019, applies her expertise in genetic technology development to address the spread of malaria and the associated economic impact. The success of Ifegenia as a suppression system surpassed her expectations.

Akbari

Akbari, a professor in the Department of Cell and Developmental Biology, expressed optimism, stating, “This technology has the potential to be the safe, controllable, and scalable solution the world urgently needs to eliminate malaria once and for all.” However, he emphasized the need to focus efforts on gaining social acceptance, regulatory approvals, and funding opportunities to test and implement this system for suppressing wild populations of malaria-transmitting mosquitoes. The researchers are determined to make a significant global impact and will persist until that goal is achieved.

The researchers also highlight that the technology behind Ifegenia has the potential for adaptation to other disease-spreading species, including mosquitoes that transmit viruses like dengue, chikungunya, and yellow fever.

Read the original article on: Phys Org

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