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Malaria kills about 2 million people annually,
mostly African children under the age of 5. While conventional
approaches to controlling the disease have been ineffective, CWRU
School of Medicine researchers are developing a genetically altered
mosquito that one day could be added to the arsenal in the war
against the disease.
 A
recent issue of the journal Nature features a paper by
a team of CWRU Department of Genetics scientists, led by Professor
of Genetics Marcelo Jacobs-Lorena that discusses research into
transgenic-or genetically altered-mosquitoes that prevent the
passage of malaria from one individual to the next.
There are thousands of types of mosquitoes,
but very few carry the malaria parasite, and only the genus, anopheles,
transmits malaria. Mosquitoes are the obligatory host for malaria
since the parasite cannot be passed from human to human. When
a mosquito ingests blood from an infected host, the parasite Plasmodium
enters the mosquito's body and goes through several transformations
before taking a form that the mosquito can pass on by biting another
person.
Jacobs-Lorena explained that when a mosquito
feeds on an infected individual, the parasite reproduces in the
mosquito's midgut and takes the form of an ookinete. The ookinetes
then move through the epithelial layer of the midgut into the
body cavity of the mosquito and mature into oocysts. After a period
of 10 to 15 days, the cysts burst and thousands of sporozoites
are released and invade the salivary glands, where they stay until
a mosquito bites the next person.
CWRU researchers created a gene-SM1-in
the laboratory that encodes a protein that interferes with the
development of the parasite in the mosquito. Scientists injected
this gene into the embryos of Anopheles stephensi mosquitoes.
The gene incorporated itself into the genome of the mosquitoes,
becoming part of the insect's DNA. The protein encoded by the
SM1 gene binds to the epithelial surface of the mosquito's midgut,
competing with the parasite and inhibiting its development by
about 80 percent. The parasites that fail to cross the midgut
die.
Another avenue researchers are pursuing
is inhibition of parasite invasion of the mosquito's salivary
glands. Future research endeavors also will test the SM1 gene
on the African mosquitoes.
This is the first time researchers have
reported blocking malaria parasite transmission by a transgenic
approach. Another researcher previously used a modified virus
to infect a mosquito and stop the spread of the parasite. But
that method had several drawbacks, including the fact that the
virus also could infect people, and the virus could not be transmitted
from one mosquito generation to the next. Once the mosquito died,
so ended the virus' capabilities in fighting malaria.
Genetically altering mosquitoes with SM1
does not affect the fitness of a mosquito, including longevity
or egg production. This is important because one of the challenges
to using insecticides is that once spraying stops a biological
niche remains. If there was a large population of mosquitoes in
an area to begin with, conditions are appropriate to sustain a
large population of the insects. If genetically modified mosquitoes
were released into an area where the local population has been
destroyed, they would occupy that niche.
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