Gene editing could render mosquitoes infertile, reducing disease spread


Date:
August 23, 2021
Source:
U.S. Army Research Laboratory
Summary:
Mosquitoes spread viruses that cause potentially deadly diseases
such as Zika, dengue fever and yellow fever. New research uses
gene editing to render certain male mosquitoes infertile and slow
the spread of these diseases.



FULL STORY ========================================================================== Mosquitoes spread viruses that cause potentially deadly diseases such
as Zika, dengue fever and yellow fever. New U.S. Army-funded research
uses gene editing to render certain male mosquitoes infertile and slow
the spread of these diseases.


========================================================================== Researchers at the Army's Institute for Collaborative Biotechnologies
and the University of California Santa Barbara used a gene editing tool
known as CRISPR-Cas9 to target a specific gene tied to fertility in
male mosquitoes.

CRISPR-Cas9 is a genome editing tool that is creating a buzz in the
science world, according to yourgenome.org. It is "faster, cheaper
and more accurate than previous techniques of editing DNA and has a
wide range of potential applications." Researchers experimented with
the Aedes aegyptimosquitoes, which are found in tropical, subtropical
and temperate regions throughout the world. The study, published in the Proceedings of the National Academy of Sciences, discerned how a mutation
can suppress the fertility of female mosquitoes.

"This is yet one more important and exciting example of how synthetic
biology tools are demonstrating unparalleled utility," said Dr. James
Burgess, ICB program manager for the U.S. Army Combat Capabilities
Development Command, now known as DEVCOM, Army Research Laboratory. "In
this case, it's a precision increase from chainsaw to a scalpel leading
to the correct biochemical outcome that could substantially reduce the population of a very infectious mosquito." To manage populations,
scientists use a vector-control practice called the sterile insect
technique in which they raise a lot of sterile male insects and
they then release these males in numbers that overwhelm their wild counterparts. Females that mate with sterile males before finding a
fertile one are themselves rendered infertile, thereby decreasing the
size of the next generation.

Repeating this technique several times has the potential to crash the population because each generation is smaller than the last; releasing
a similar number of sterile males has a stronger effect over time.



==========================================================================
The sterile insect technique is effective in managing a number of
agricultural pests, including the Mediterranean fruit fly, a crop pest
in California. It has also been attempted with Aedes aegypti mosquitoes,
but with limited success.

In the past, scientists used chemicals or radiation to sterilize male
Aedes aegypti, but the chemicals or radiation impacted the mosquitoes'
health to such an extent that they were less successful in mating
with females, which undercuts the effectiveness of the sterile insect technique.

The research team wanted to identify a more targeted approach with less collateral damage, mutating a gene in mosquitoes that specifically caused
male sterility without otherwise impacting the insects' health.

"When CRISPR/Cas9 came out several years ago it just offered new
opportunities to do things that you couldn't do before," said Dr. Craig Montell, distinguished professor at UC Santa Barbara. "So, the time
seemed right to for us to start working on Aedes aegypti." Using gene
editing in male Aedes aegypti, researchers found that the mutant male mosquitoes produced no sperm, and unlike in previous efforts, the sterile
studs were otherwise completely healthy; however, the team wasn't sure
whether sperm, albeit defective sperm from the sterile males, was needed
to render female mosquitoes infertile, or whether the transfer of seminal
fluid was all it took.



==========================================================================
In one experiment, researchers introduced 15 mutant males into a group
of 15 females for 24 hours. Then they swapped the males for 15 wild-type
males, and left them there.

"Essentially, all of the females remained sterile," Montell said. "This confirmed that males could suppress female fertility without producing
sperm." Next the researchers set out to determine how timing played
into the effect.

They exposed the females to mutant males for different lengths of
time. The scientists noticed little difference after 30 minutes, but
female fertility quickly dropped after that. Montell noted that females copulated twice on average, even during the first 10 minutes. This
indicated that females have to mate with many sterile males before being rendered infertile themselves.

Combining the females with the males for four hours cut female fertility
to 20% of normal levels. After eight hours the numbers began leveling
out around 10%.

According to Montell, Aedes aegypti populations could easily bounce back
from an 80% drop in fertility. The success of sterile insect technique
comes from subsequent, successive releases of sterile males, where each
release will be more effective than the last as sterile males account
for an ever-growing proportion of the population.

The team plans to continue investigating mosquito mating behaviors and fertility. They are devising a way to maintain stocks of males so they
are only sterile in the wild and not in the lab. In addition, they are characterizing male mating behavior to uncover new ways to suppress
mosquito populations.

"We've become very interested in studying many aspects of behavior
in Aedes aegypti because these mosquitoes impact the health of so many
people," Montell said. "There is a pandemic every year from mosquito-borne diseases.

========================================================================== Story Source: Materials provided by U.S._Army_Research_Laboratory. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Jieyan Chen, Junjie Luo, Yijin Wang, Adishthi S. Gurav, Ming Li,
Omar S.

Akbari, Craig Montell. Suppression of female fertility in Aedes
aegypti with a CRISPR-targeted male-sterile mutation. Proceedings
of the National Academy of Sciences, 2021; 118 (22): e2105075118
DOI: 10.1073/ pnas.2105075118 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/08/210823110325.htm

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