New genetic technology developed to halt malaria-spreading mosquitoes
As envisioned, first-of-its-kind African mosquito suppression system
would reduce child mortality and aid economic development

Date:
July 5, 2023
Source:
University of California - San Diego
Summary:
Using CRISPR technology, scientists have engineered a new way
to genetically suppress populations of Anopheles gambiae, the
mosquitoes that primarily spread malaria in Africa and contribute
to economic poverty in affected regions.


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FULL STORY ========================================================================== Malaria remains one of the world's deadliest diseases. Each year
malaria infections result in hundreds of thousands of deaths, with the
majority of fatalities occurring in children under five. The Centers
for Disease Control and Prevention recently announced that five cases
of mosquito-borne malaria were detected in the United States, the first reported spread in the country in two decades.

Fortunately, scientists are developing safe technologies to stop the transmission of malaria by genetically editing mosquitoes that spread
the parasite that causes the disease. Researchers at the University
of California San Diego led by Professor Omar Akbari's laboratory have engineered a new way to genetically suppress populations of Anopheles
gambiae, the mosquitoes that primarily spread malaria in Africa and
contribute to economic poverty in affected regions. The new system
targets and kills females of the A. gambiae population since they bite
and spread the disease.

Publishing July 5 in the journal Science Advances, first-author Andrea
Smidler, a postdoctoral scholar in the UC San Diego School of Biological Sciences, along with former master's students and co-first authors
James Pai and Reema Apte, created a system called Ifegenia, an acronym
for "inherited female elimination by genetically encoded nucleases to
interrupt alleles." The technique leverages the CRISPR technology to
disrupt a gene known as femaleless (fle) that controls sexual development
in A. gambiae mosquitoes.

Scientists at UC Berkeley and the California Institute of Technology contributed to the research effort.

Ifegenia works by genetically encoding the two main elements of CRISPR
within African mosquitoes. These include a Cas9 nuclease, the molecular "scissors" that make the cuts and a guide RNA that directs the system to
the target through a technique developed in these mosquitoes in Akbari's
lab. They genetically modified two mosquito families to separately
express Cas9 and the fle-targeting guide RNA.

"We crossed them together and in the offspring it killed all the female mosquitoes," said Smidler, "it was extraordinary." Meanwhile, A. gambiae
male mosquitoes inherit Ifegenia but the genetic edit doesn't impact their reproduction. They remain reproductively fit to mate and spread Ifegenia.

Parasite spread eventually is halted since females are removed and the population reaches a reproductive dead end. The new system, the authors
note, circumvents certain genetic resistance roadblocks and control
issues faced by other systems such as gene drives since the Cas9 and
guide RNA components are kept separate until the population is ready to
be suppressed.

"We show that Ifegenia males remain reproductively viable, and can
load both flemutations and CRISPR machinery to induce flemutations in subsequent generations, resulting in sustained population suppression,"
the authors note in the paper. "Through modeling, we demonstrate that
iterative releases of non- biting Ifegenia males can act as an effective, confinable, controllable and safe population suppression and elimination system." Traditional methods to combat malaria spread such as bed nets
and insecticides increasingly have been proven ineffective in stopping
the disease's spread.

Insecticides are still heavily used across the globe, primarily in an
effort to stop malaria, which increases health and ecological risks to
areas in Africa and Asia.

Smidler, who earned a PhD (biological sciences of public health) from
Harvard University before joining UC San Diego in 2019, is applying her expertise in genetic technology development to address the spread of
the disease and the economic harm that comes with it. Once she and her colleagues developed Ifegenia, she was surprised by how effective the technology worked as a suppression system.

"This technology has the potential to be the safe, controllable and
scalable solution the world urgently needs to eliminate malaria once
and for all," said Akbari, a professor in the Department of Cell
and Developmental Biology. "Now we need to transition our efforts
to seek social acceptance, regulatory use authorizations and funding opportunities to put this system to its ultimate test of suppressing
wild malaria-transmitting mosquito populations. We are on the cusp of
making a major impact in the world and won't stop until that's achieved."
The researchers note that the technology behind Ifegenia could be adapted
to other species that spread deadly diseases, such as mosquitoes known to transmit dengue (break-bone fever), chikungunya and yellow fever viruses.

The full author list includes Andrea Smidler, James Pai, Reema Apte,
Hector Sanchez C., Rodrigo Corder, Eileen Jeffrey Gutierrez, Neha Thakre,
Igor Antoshechkin, John Marshall and Omar Akbari.

* RELATED_TOPICS
o Health_&_Medicine
# Malaria # Diseases_and_Conditions # Ebola # Genes
o Plants_&_Animals
# Insects_(including_Butterflies) # Pests_and_Parasites #
Biochemistry_Research # CRISPR_Gene_Editing
* RELATED_TERMS
o Malaria o Transgenic_plants o Tropical_disease o Pest_(animal)
o Genetically_modified_organism o Genetically_modified_food
o Cholera o Agroecology

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========================================================================== Journal Reference:
1. Andrea L. Smidler, James J. Pai, Reema A. Apte, He'ctor M. Sa'nchez
C.,
Rodrigo M. Corder, Eileen Jeffrey Gutie'rrez, Neha Thakre, Igor
Antoshechkin, John M. Marshall, Omar S. Akbari. A confinable
female- lethal population suppression system in the malaria
vector, Anopheles gambiae. Science Advances, 2023; 9 (27) DOI:
10.1126/sciadv.ade8903 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2023/07/230705154012.htm

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