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ANIMALS: Malaria-resistant mosquitoes



                                 PART I
------------------------------- GENET-news -------------------------------
TITLE:  Malaria-resistant mosquitoes outbreed others-study
SOURCE: Reuters
AUTHOR:
URL:    http://www.reuters.com/article/homepageCrisis/idUSN19278328._CH_.2400
DATE:   19.03.2007
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Malaria-resistant mosquitoes outbreed others-study

WASHINGTON, March 19 (Reuters) - Mosquitoes genetically engineered to
resist infection with a malaria parasite outbreed their normal cousins
and might be used to help control malaria, U.S. researchers said on Monday.

They said their study suggests that releasing such genetically altered
insects could help battle malaria, which kills up to 3 million people a
year around the globe, most of them small children.

Marcelo Jacobs-Lorena and colleagues at Johns Hopkins University in
Baltimore studied mosquitoes with an extra gene spliced in that helps
stop them from transmitting the Plasmodium berghei parasite.

Previous studies have already shown that these mosquitoes are perfectly
healthy.

Jacobs-Lorena and colleagues studied the mosquitoes as they bred in
cages. The mosquitoes were allowed to feed on mice that had been
infected with P. berghei, one of the parasites that causes malaria.

The transgenic mosquitoes were more fertile and less likely to die than
normal, wild mosquitoes, they report in this week's issue of the
Proceedings of the National Academy of Sciences.

They also began to outbreed the normal mosquitoes.

"To our knowledge, no one has previously reported a demonstration that
transgenic mosquitoes can exhibit a fitness advantage over
nontransgenics," the researchers wrote.

They ran a computer program projecting how much better the gene-
engineered mosquitoes would do and it predicted engineered insects would
have a 50 percent better survival rate.

P. berghei is not the most serious cause of malaria -- another parasite
called Plasmodium falciparum is. But the researchers said their study
shows the idea of using lab-engineered mosquitoes to battle malaria is a
valid one.


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                                 PART II
------------------------------- GENET-news -------------------------------
TITLE:  Malaria-resistant mosquitoes
SOURCE: Massachusetts Institute of Technology, USA
AUTHOR: Technology Review, USA, by Corinna Wu
URL:    http://www.technologyreview.com/Biotech/18407/
DATE:   20.03.2007
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..........................................................................
More work needs to be done before transgenic mosquitoes can be used in the
field as a malaria-control method. "Transgenic mosquitoes by themselves
will never be able to solve the problem," Jacobs-Lorena says. "The only
way is to use a combination of approaches: a coordinated attack using
drugs, insecticides, transgenic mosquitoes, and perhaps vaccines. Then we
have a chance to make a significant change in the transmission of the
disease. No one should think of this as a silver bullet."
..........................................................................


Malaria-resistant mosquitoes

Researchers show that benign, genetically engineered mosquitoes can
outcompete disease-causing ones, suggesting a possible way to control
the disease.

Mosquitoes genetically engineered for malaria resistance can outcompete
their wild counterparts--at least in the lab, according to researchers
at Johns Hopkins University. While previous studies have described the
creation of malaria-resistant mosquitoes, this is the first time that
researchers have shown a reproductive advantage for the genetically
engineered organisms, which is an important requirement if such
mosquitoes are to be used as a practical malaria-control strategy.

Malaria kills more than a million people worldwide each year, most of
them children in sub-Saharan Africa, according to the World Health
Organization. The disease is caused by Plasmodium parasites, protozoa
that are transmitted from person to person by female Anopheles
mosquitoes. Researchers have proposed a method of controlling the spread
of malaria by introducing into the wild mosquitoes that can't transmit
the parasite, but computer models suggest that malaria-resistant
mosquitoes must almost completely replace the native population in order
to stop the cycle of transmission.

In the current study, Marcelo Jacobs-Lorena and his colleagues at the
Johns Hopkins School of Public Health, in Baltimore, put equal numbers
of malaria-resistant mosquitoes and ordinary mosquitoes in a cage and
allowed them to feed on mice infected with the malaria-causing parasite.
The researchers then collected the eggs laid by the insects, reared them
into adulthood, and allowed the new generation of mosquitoes to feed on
infected mice.

After nine generations, 70 percent of the mosquitoes were malaria
resistant, meaning that the genetically engineered insects had largely
outcompeted their nonresistant counterparts. In contrast, mosquitoes
that fed on uninfected mice did not show any fitness differences. The
researchers published their findings in the early online edition of the
Proceedings of the National Academy of Sciences.

Earlier work by Hillary Hurd, a parasitologist at Keele University, in
the United Kingdom, showed that infection with Plasmodium affects
mosquitoes' fertility. "There's a fitness cost to being infected," Hurd
says, so mosquitoes that are protected from infection should have an
advantage over those that aren't protected. The results of the Johns
Hopkins study support that conclusion, she says.

Researchers have created different types of malaria-resistant mosquitoes
by interfering with the Plasmodium parasite's complex developmental
cycle. After a mosquito ingests the parasite from infected blood, the
parasite invades the mosquito's gut and forms a cyst. That cyst
eventually ruptures and releases spores into the mosquito's body, which
migrate to the salivary glands. Then, when the mosquito bites another
person, it transmits the parasite.

Jacobs-Lorena and his colleagues engineered mosquitoes to produce a
peptide called SM1 that blocks Plasmodium from invading the mosquito's
gut, thus interrupting the parasite's development. Since it is not a
naturally occurring peptide, SM1 doesn't activate the mosquito's immune
system, according to Hurd. "This is a very different strategy than what
other groups are working on," she says. "If you induce an immune
response ... there is a fitness cost too."

Unlike other groups that conducted experiments, the researchers bred the
genetically engineered mosquitoes with ordinary ones, so the insects in
their study had just one copy of the SM1 gene instead of two. "Our
hypothesis is that there are many genes throughout the genome that
confer fitness disadvantage, but they're recessive," says Jacobs-Lorena.
So in mosquitoes engineered to have two copies of SM1, the traits coded
by those recessive genes express themselves and reduce the fitness of
the mosquitoes. Having just one copy of SM1 doesn't seem to reduce the
insects' resistance to the malaria parasite, he adds.

Hurd cautions that the malaria-causing parasites used by the Johns
Hopkins team infect mice, not humans. "Anyone taking this strategy needs
to be certain that the molecule stops transmission of the human
parasite," she says. "Many of them don't."

More work needs to be done before transgenic mosquitoes can be used in
the field as a malaria-control method. "Transgenic mosquitoes by
themselves will never be able to solve the problem," Jacobs-Lorena says.
"The only way is to use a combination of approaches: a coordinated
attack using drugs, insecticides, transgenic mosquitoes, and perhaps
vaccines. Then we have a chance to make a significant change in the
transmission of the disease. No one should think of this as a silver bullet."


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                                 PART III
------------------------------- GENET-news -------------------------------
TITLE:  Malaria: GM mosquitoes offer new hope for millions
SOURCE: The Guardian, UK
AUTHOR: Ian Sample
URL:    http://www.guardian.co.uk/international/story/0,,2037909,00.html
DATE:   20.03.2007
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...........................................................................
"This has tremendous potential. You can start with a few mosquitoes and
in future generations, all of them are resistant to the disease. It
should be much cheaper than the controls used now, because you have a
strategy where the mosquito spreads the gene which confers resistance.
You don't need insecticides any more," he [Andrea Crisanti, who leads a
team working on GM mosquitoes at Imperial College, London] said.
...........................................................................


Malaria: GM mosquitoes offer new hope for millions
Controversial strategy would mean releasing laboratory-created insects
into wild

The multimillion-dollar effort to eradicate one of the world's deadliest
diseases received a significant but controversial boost yesterday when
scientists announced the creation of genetically modified mosquitoes
that cannot pass on malaria.

Trials revealed that the GM mosquitoes could quickly establish
themselves in the wild and drive out natural malaria-carrying insects,
thereby breaking the route through which humans are infected.

The strategy is likely to prove contentious as it would require the
unprecedented release of tens of thousands of GM organisms into the
wild. But it has raised hopes among scientists, some of whom believe it
may be powerful enough to finally bring under control a disease which
strikes 300 million people a year and causes more than 1 million deaths,
mostly of children in sub-Saharan Africa.

Plans to combat malaria with disease-resistant mosquitoes have been
hampered in the past by fears that adding crucial resistance genes
weakens the insects, making them too feeble to survive in the wild. For
the idea to work, the malaria-resistant insects must breed and become
dominant, so that the parasite is not picked up from infected animals
and passed on to humans through insect bites.

Researchers led by Marcelo Jacobs-Lorena at the Malaria Research
Institute at Johns Hopkins University in Maryland created genetically
modified mosquitoes by giving them a gene that made it impossible for
them to pass on the plasmodium parasite that causes malaria. Around
1,200 GM mosquitoes were then released into a cage holding malaria-
infected mice and the same number of wild mosquitoes.

Over time, the researchers found that the GM mosquitoes slowly became
the majority, reaching 70% in nine generations. The scientists believe
that even though malaria-resistance weakened the mosquitoes by making
them immune to the parasite, they fared better in the long term than
insects infected with it because they lived longer and laid more eggs.

"This fitness advantage has important implications for devising malaria
control strategies," the team write in the journal Proceedings of the
National Academy of Sciences.

The finding was hailed as welcome proof that GM mosquitoes, made with
cheap laboratory techniques, could ultimately have a greater impact on
malaria than chemical sprays and other treatments.

Andrea Crisanti, who leads a team working on GM mosquitoes at Imperial
College, London, said the latest work raised hopes by showing the
insects would be unlikely to die out if released into the wild.

"This has tremendous potential. You can start with a few mosquitoes and
in future generations, all of them are resistant to the disease. It
should be much cheaper than the controls used now, because you have a
strategy where the mosquito spreads the gene which confers resistance.
You don't need insecticides any more," he said.

In wild populations, only a small fraction of females carry the malaria
parasite, so disease-resistant strains must become well-established to
affect the spread of disease. Scientists are focusing on ways to perfect
how resistance genes are inherited, ensuring they are passed on in every
mosquito egg. Normally, offspring have a 50% chance of inheriting a
specific gene from the mother.

Trials in sub-Saharan Africa, where malaria claims the life of a child
every 30 seconds, could be conducted within five years, but scientists
will first have to prove as far as possible that the resistance genes
will not trigger a more aggressive form of malaria, or spread to other
insects.


At a glance
- Malaria kills more than 1 million people a year
- 90% of malaria deaths occur among young children in sub-Saharan Africa
- The disease costs Africa $12bn (6.2bn) in lost GDP and consumes 40%
of public health spending
- 60% of malaria deaths strike the poorest 20% of the global population
- 71% of all deaths from malaria are in the under-fives
- Children can die within 48 hours after the first symptoms appear after
the first symptoms appear


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