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UCSD team helps develop gene-editing method to block mosquitoes from spreading Malaria

Mosquito Illnesses
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SAN DIEGO (CNS) — A team of scientists, including researchers at UC
San Diego, have developed a gene-editing method to block mosquitoes from
spreading malaria, it was announced today.

Biologists Zhiqian Li and Ethan Bier from UCSD, and Yuemei Dong and
George Dimopoulos from Johns Hopkins University, created a CRISPR-based gene-editing system that ``changes a single molecule within mosquitoes, a minuscule but effective change that stops the malaria-parasite transmission process,'' a statement from the researchers read.

``Replacing a single amino acid in mosquitoes with another naturally
occurring variant that prevents them from being infected with malarial
parasites -- and spreading that beneficial trait throughout a mosquito
population -- is a game-changer,'' said Bier, a professor in UCSD's Department
of Cell and Developmental Biology. ``It's hard to believe that this one tiny
change has such a dramatic effect.''

Mosquitoes are the deadliest animal on Earth. In 2023 alone, they
infected 263 million people with malaria, resulting in nearly 600,000 deaths --
80% of them children.

Efforts to fight the disease have been hindered by growing insecticide
resistance and increased resistance to malaria drugs. These setbacks were
made worse by the COVID-19 pandemic, which disrupted global anti-malaria
programs.

Rather than targeting the parasite directly, the research team --
which includes members from UC San Diego, Johns Hopkins, UC Berkeley, and the University of Sao Paulo -- modified mosquito genes to stop them from passing on the parasite when they bite.

Genetically modified mosquitoes can still bite and take in parasites
from infected humans, but they no longer transmit those parasites to others.
The key: a switch in a single amino acid that prevents the malaria parasite
from reaching the mosquito's salivary glands, which is essential for
transmission.

``The new system is designed to genetically spread the malaria
resistance trait until entire populations of the insects no longer transfer the
disease-causing parasites,'' a statement from UCSD read.

``The beauty of this approach lies in leveraging a naturally occurring
mosquito gene allele,'' said Dimopoulos, a professor at the Johns Hopkins
Malaria Research Institute.

``With a single, precise tweak, we've turned it into a powerful shield
that blocks multiple malaria parasite species and likely across diverse
mosquito species and populations, paving the way for adaptable, real-world
strategies to control this disease.''

In additional testing, the researchers found that ``although the
genetic switch disrupted the parasite's infection capabilities, the mosquitoes'
normal growth and reproduction remained unchanged.''

The insects carrying the newly inserted gene exhibited similar fitness
to those with the original amino acid. The researchers created a technique for mosquito offspring to genetically inherit the altered allele and spread it throughout their populations. This ``allelic-drive'' follows a similar system recently engineered in the Bier Lab that genetically reverses insecticide resistance in crop pests.

``In that prior study, we created a self-eliminating drive that
converts a population of fruit flies from being resistant to insecticides back
to its native insecticide-susceptible state,'' Bier said. ``Then that genetic
cassette just disappears, leaving only a re-wilded insect population.''
Researchers are continuing to study why this single amino acid switch
is so effective, and how exactly it prevents the malaria parasite from
migrating within the mosquito.