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[genet-news] SCIENCE & ANIMALS: University of Arizona (USA) researchers engineer malaria-proof GE mosquito



                                  PART 1


------------------------------- GENET-news -------------------------------

TITLE:   UA RESEARCHERS ENGINEER MALARIA-PROOF MOSQUITO

SOURCE:  The Arizona Republic, USA

AUTHOR:  Anne Ryman

URL:     http://www.azcentral.com/arizonarepublic/news/articles/2010/07/16/20100716ua-researchers-create-malaria-proof-mosquito.html

DATE:    16.07.2010

SUMMARY: "Researchers at the University of Arizona have genetically engineered the first ?supermosquito? that is immune to malaria contracted by humans, a finding that could eventually help wipe out the deadly disease. Previous experiments by other scientists resulted in mosquitoes that were nearly immune to the parasite that causes human malaria. But to stop the spread of disease, scientists need insects that are 100 percent immune, said Michael Riehle, a UA professor who led the research."

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UA RESEARCHERS ENGINEER MALARIA-PROOF MOSQUITO

Researchers at the University of Arizona have genetically engineered the first ?supermosquito? that is immune to malaria contracted by humans, a finding that could eventually help wipe out the deadly disease.

Previous experiments by other scientists resulted in mosquitoes that were nearly immune to the parasite that causes human malaria. But to stop the spread of disease, scientists need insects that are 100 percent immune, said Michael Riehle, a UA professor who led the research.

?The idea is to actually replace the wild-mosquito population with one that?s not able to transmit malaria,? he said.

That step could take at least a decade because the scientific community must develop a genetic mechanism that would give supermosquitoes an advantage over wild mosquitoes, Riehle said. An example would be immune mosquitoes whose offspring with wild ones are more likely to inherit immunity. Scientists also must study how immunity affects mosquitoes? behavior and coordinate with local governments to set up test sites.

For now, the immune mosquitoes are kept in a secure lab on the UA campus, with Riehle and his collaborators at the University of California-Davis and the University of Georgia celebrating the breakthrough. Their results were published Thursday in the Public Library of Science Pathogens, a peer-reviewed journal.

Malaria is caused by a parasite transmitted by certain species of female mosquitoes. The disease is rare in the United States but common in tropical countries. An estimated 247 million people come down with malaria every year, and 1 million, mostly children, die. There is no effective vaccine, but the disease can be treated with drugs.

Riehle has been working on a malaria-immune mosquito for about seven years.

To accomplish this, scientists needed to alter the insect?s genetic makeup. They targeted a cell enzyme, known as Akt, which is involved in the mosquito?s immune response, and changed the genetic information to ramp up its function.

This new DNA was injected into thousands of mosquito eggs, creating a potential group of supermosquitoes that scientists could study along with a control group. They fed both groups the malaria parasite. After 10 days, they dissected the insects and looked for signs of the parasite. The genetically altered mosquitoes showed no signs of infection.

Riehle isn?t sure exactly why the parasites don?t survive in the immune mosquitoes. He said he has some theories that he isn?t ready to disclose, but the next step in research is to answer that question.

Research funding, which is shared among the three universities, comes from a $2.8 million grant from the National Institutes of Health.



                                  PART 2

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TITLE:   CREATED BY GENETIC ENGINEERING, A MOSQUITO THAT CAN?T CATCH MALARIA

SOURCE:  The Independent, UK

AUTHOR:  Jeremy Laurance

URL:     http://www.independent.co.uk/life-style/health-and-families/health-news/created-by-genetic-engineering-a-mosquito-that-cant-catch-malaria-2027818.html

DATE:    16.07.2010

SUMMARY: "Researchers at the University of Arizona have created a genetically modified insect that is incapable of transmitting the disease to humans.

The advance could lead to the release of modified mosquitoes into malarial regions of the world to prevent the transmission of one of the world?s biggest killers. [...] Michael Riehle, an entomologist who led the research said: ?We were surprised how well this works. We were just hoping to see some effect on the mosquitoes? growth rate, lifespan or their susceptibility to the parasite, but it was great to see that our construct blocked the infection process completely.?"

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CREATED BY GENETIC ENGINEERING, A MOSQUITO THAT CAN?T CATCH MALARIA

Researchers at the University of Arizona have created a genetically modified insect that is incapable of transmitting the disease to humans.

The advance could lead to the release of modified mosquitoes into malarial regions of the world to prevent the transmission of one of the world?s biggest killers.

Malaria infects an estimated 250 million people a year and causes nearly a million deaths, mostly among children under five.

Michael Riehle, an entomologist who led the research said: ?We were surprised how well this works. We were just hoping to see some effect on the mosquitoes? growth rate, lifespan or their susceptibility to the parasite, but it was great to see that our construct blocked the infection process completely.?

The development potentially provides a new method of tackling the disease. Most efforts rely on controlling mosquitoes by spraying insecticide and using bed nets, or on treating victims with anti-malarial drugs.

Not all mosquitoes transmit malaria ? only the female anopheles, of which there are about 25 species. They feed on blood and each time they bite an infected human or animal they ingest malaria parasites. These later migrate to the salivary glands and the disease is passed on in the next bite.

To break this life cycle, the Arizona scientists inserted a gene to enhance the action of the enzyme Akt which is involved in the mosquito?s growth rate and immune function. The aim was to ramp up Akt function to help the insect?s immune system fight off the malaria parasite, and to cut its lifespan, because mosquitoes only become capable of transmitting malaria towards the end of their lives.

?In the wild, a mosquito lives for an average of two weeks. Only the oldest mosquitoes are able to transmit the parasite,? Dr Riehle said. ?If we can reduce their lifespan, we can reduce the number of infections.?

Studies showed that modified mosquitoes carrying two copies of the altered gene had lost their ability to transmit malaria altogether. However, to be effective in the battle to control malaria, the modified mosquitoes must be given an advantage over natural populations of the insects so that they can compete with and, over time, displace them. At present they exist only in high security laboratories with no chance of escape.

Dr Riehle said this was the hardest task. ?It is going to be the most difficult to realise,? he said, which is why it had been left to last.

Chris Drakeley, director of the Malaria Centre at the London School for Hygiene and Tropical Medicine, said: ?Advances of this kind are very welcome because they help us understand the biology of the disease. But they are still a long way from helping with control. To do that they have to test if the fitter mosquito can drive out the existing ones. And then they would face ethical and community acceptance challenges ? if you tell people you plan to introduce a new mosquito they are liable to respond ?not in my village?.

?It is still early days [for the malaria-proof mosquito]. We are considerably more advanced with the development of malaria vaccines. But we will need a variety of tools in the toolbox to tackle the disease everywhere ? from urban India to the African savannah.?



                                  PART 3

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TITLE:   ERADICATING THIS BIBLICAL PLAGUE IS BECOMING POSSIBLE

SOURCE:  The Independent, UK

AUTHOR:  Jeremy Laurance

URL:     http://www.independent.co.uk/opinion/commentators/jeremy-laurance-eradicating-this-biblical-plague-is-becoming-possible-2027819.html

DATE:    16.07.2010

SUMMARY: "The achievement of Michael Riehle and his team at the University of Arizona is impressive. But by their own admission, they have done the easy bit ? create a genetically modified mosquito that cannot transmit malaria. To help with controlling the disease, the GM mosquito must first be proved safe for release into the wild and, second, must be given some advantage that renders it superior to natural populations so it can drive them out. That is much harder to do."

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ERADICATING THIS BIBLICAL PLAGUE IS BECOMING POSSIBLE

It looks ingenious. If you can?t eradicate malaria in humans, why not do so in mosquitoes? It would accomplish a goal of which scientists hardly dared dream: a malaria-free world.

The achievement of Michael Riehle and his team at the University of Arizona is impressive. But by their own admission, they have done the easy bit ? create a genetically modified mosquito that cannot transmit malaria.

To help with controlling the disease, the GM mosquito must first be proved safe for release into the wild and, second, must be given some advantage that renders it superior to natural populations so it can drive them out. That is much harder to do.

Despite these caveats, and the dreadful toll malaria still exacts, there are reasons to celebrate. Action against malaria ? spraying of insecticide, distribution of bed nets and use of anti-malarial drugs ? has increased dramatically in the last decade as global funding has expanded 50-fold to over $5bn in 2009. In coastal areas of Kenya, cases of severe malaria in children have fallen by 90 per cent in five years. Similar falls have been reported from other locations.

In certain islands in the Philippines, malaria has been eliminated. Mexico is said to be close to eradication, countries in South America are moving in the same direction and Morocco is expected to announce the end of the disease soon.

Sub-Saharan Africa, which bears 70 per cent of the disease burden, presents a much tougher challenge. But in the global malaria community ? where gloom prevailed a decade ago ? the buzzword now is elimination. As The Lancet noted this month, ?previously cautious malariologists, released from a 40-year collective depression... have been invigorated?.

Talk of elimination may be premature ? the funds required to chase down the last few cases of a disease are several orders of magnitude higher than those needed to control it ? as the polio eradication campaign has proved. But that we can envisage the end of a disease that still kills in biblical proportions is itself a remarkable advance.



                                  PART 4

------------------------------- GENET-news -------------------------------

TITLE:   BITE ME: NEW MALARIA-PROOF MOSQUITO DEVELOPED

SOURCE:  Scientific American, USA

AUTHOR:  Nicholette Zeliadt

URL:     http://www.scientificamerican.com/blog/post.cfm?id=bite-me-new-malaria-proof-mosquito-2010-07-15

DATE:    15.07.2010

SUMMARY: "An estimated one million people die each year from malaria, a parasitic infection transmitted by mosquitoes. Current control strategies involve blasting the bugs with insecticides, or using drugs to kill the parasite once it infects humans. Unfortunately, these methods are becoming less effective as both pests evolve ways to resist the toxic treatments, so new methods to prevent malaria are sorely needed."

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BITE ME: NEW MALARIA-PROOF MOSQUITO DEVELOPED

An estimated one million people die each year from malaria, a parasitic infection transmitted by mosquitoes. Current control strategies involve blasting the bugs with insecticides, or using drugs to kill the parasite once it infects humans. Unfortunately, these methods are becoming less effective as both pests evolve ways to resist the toxic treatments, so new methods to prevent malaria are sorely needed. In recent years, scientists have tinkered with the insect?s genes with hopes of developing modified mosquitoes incapable of transmitting the parasite. While promising, these efforts produced mosquitoes with only reduced parasite transmission. Now, researchers led by University of Arizona entomology professor Michael Riehle report that they have developed a transgenic mosquito that is completely immune to infection by Plasmodium falciparum, the primary malaria-causing parasite in humans. The researchers hope that their findings will one day be used as part of a new strategy t
 o combat malaria.

For malaria to spread, a female Anopheles mosquito must first ingest the parasite by dining on an infected person. Once inside the mosquito, the parasite undergoes an approximately two-week maturation process, traveling from the mosquito gut to the salivary gland where it is then ready to be spread to other human hosts.

Fortunately for humans, mosquitoes in malaria-endemic regions rarely survive more than two weeks. Therefore, the researchers sought to investigate ways to shorten the mosquito?s lifespan because ?even a modest reduction in lifespan could significantly impact parasite transmission,? the authors wrote in their paper, published online July 15 in PLoS Pathogens.

The researchers used information that has been learned by studying longevity and immunity in other model organisms, particularly fruit flies and nematodes, to target a gene in the mosquito suspected to control mosquito lifespan and regulate its resistance to infection. The team engineered the mosquitoes to express high levels of the active form of a protein known as Akt, and found that the transgenic mosquitoes not only had a shorter lifespan?approximately 20 percent shorter than controls?parasite infection was completely blocked.

?We were surprised how well this works,? Riehle said, in a prepared statement. ?We were just hoping to see some effect on the mosquitoes? growth rate, lifespan or their susceptibility to the parasite, but it was great to see that our construct blocked the infection process completely.?

This is an important first step because it only takes one parasite to make a mosquito infective?if even a single parasite survives, it can go on to produce thousands of progeny, Riehle says. He adds that his team would like to figure out how the parasites are being killed because that information could be used to make even more resistant mosquitoes.

In order for any transgenic mosquito to be truly effective against malaria, however, the transgenic bugs will have to out-compete wild mosquitoes and eventually displace them, a significant challenge that Riehle acknowledges and hopes to tackle in the future. Until that happens, Riehle?s genetically modified mosquitoes are safely secured in his lab.



                                  PART 5

------------------------------- GENET-news -------------------------------

TITLE:   THE FIRST MALARIA-PROOF MOSQUITO

SOURCE:  University of Arizona, USA

AUTHOR:  Press Release

URL:     http://uanews.org/node/32833

DATE:    15.07.2010

SUMMARY: "University of Arizona entomologists have succeeded in genetically altering mosquitoes in a way that renders them completely immune to the parasite, a single-celled organism called Plasmodium. [...] ?If you want to effectively stop the spreading of the malaria parasite, you need mosquitoes that are no less than 100 percent resistant to it. If a single parasite slips through and infects a human, the whole approach will be doomed to fail,? said Michael Riehle, who led the research effort,"

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THE FIRST MALARIA-PROOF MOSQUITO

UA scientists have achieved a breakthrough in the fight against malaria: a mosquito that can no longer give the disease to humans.

For years, researchers worldwide have attempted to create genetically altered mosquitoes that cannot infect humans with malaria. Those efforts fell short because the mosquitoes still were capable of transmitting the disease-causing pathogen, only in lower numbers.

Now for the first time, University of Arizona entomologists have succeeded in genetically altering mosquitoes in a way that renders them completely immune to the parasite, a single-celled organism called Plasmodium. Someday researchers hope to replace wild mosquitoes with lab-bred

populations unable to act as vectors, i.e. transmit the malaria-causing parasite.

?If you want to effectively stop the spreading of the malaria parasite, you need mosquitoes that are no less than 100 percent resistant to it. If a single parasite slips through and infects a human, the whole approach will be doomed to fail,? said Michael Riehle, who led the research effort, the results of which were published July 15 in the journal Public Library of Science Pathogens.

Riehle is a professor of entomology in UA?s College of Agriculture and Life Sciences and is a member of the BIO5 Institute.

Riehle?s team used molecular biology techniques to design a piece of genetic information capable of inserting itself into a mosquito?s genome. This construct was then injected into the eggs of the mosquitoes. The emerging generation carries the altered genetic information and passes it on to future generations.

For their experiments, the scientists used Anopheles stephensi, a mosquito species that is an important malaria vector throughout the Indian subcontinent.

The researchers targeted one of the many biochemical pathways inside the mosquito?s cells. Specifically, they engineered a piece of genetic code acting as a molecular switch in the complex control of metabolic functions inside the cell. The genetic construct acts like a switch that is always set to ?on,? leading to the permanent activity of a signaling enzyme called Akt. Akt functions as a messenger molecule in several metabolic functions, including larval development, immune response and lifespan.

When Riehle and his co-workers studied the genetically modified mosquitoes after feeding them malaria-infested blood, they noticed that the Plasmodium parasites did not infect a single study animal.

?We were surprised how well this works,? said Riehle. ?We were just hoping to see some effect on the mosquitoes? growth rate, lifespan or their susceptibility to the parasite, but it was great to see that our construct blocked the infection process completely.?

Of the estimated 250 million people who contract malaria each year, 1 million ? mostly children ? do not survive. Ninety percent of the number of fatalities, which Riehle suspects to be underreported, occur in sub-Saharan Africa.

Each new malaria case starts with a bite from a vector ? a mosquito belonging to the genus Anopheles. About 25 species of Anopheles are significant vectors of the disease.

Only the female Anopheles mosquitoes feed on blood, which they need to produce eggs. When they bite an infected human or animal, they ingest the malaria parasite.

Once the Plasmodium cells find themselves in the insect?s midgut, they spring into action. They leave the insect?s digestive tract by squeezing through the midgut lining. The vast majority of Plasmodium cells do not survive this journey and are eliminated by the mosquito?s immune cells. A tiny fraction of parasite cells, usually not more than a handful, make it and attach themselves on the outside of the midgut wall where they develop into brooding cells called oocysts.

Within 10-12 days, thousands of new Plasmodium cells, so-called sporozoites, sprout inside the oocyst. After hatching from the oocyst, the sporozoites make their way into the insect?s salivary glands where they lie in wait until the mosquito finds a victim for a blood meal. When the mosquito bites, some sporozoites are flushed into the victim?s bloodstream.

?The average mosquito transmits about 40 sporozoites when it bites,? said Riehle, ?but it takes only one to infect a human and make a new malaria victim.?

Several species of Plasmodium exist in different parts of the world, all of which are microscopically small single-celled organisms that live in their host?s red blood cells. Each time the parasites undergo a round of multiplication, their host cells burst and release the progeny into the bloodstream, causing the painful bouts of fever that malaria is known and feared for.

Malaria killed more soldiers in the Civil War than the fighting, according to Riehle. In fact, malaria was prevalent in most parts of the U.S. until the late 1940s and early 1950, when DDT spraying campaigns wiped the vectors off the map. Today, a new case of malaria occurs in the U.S. only on rare occasions.

The severity of the disease depends very largely on the species of the Plasmodium parasite the patient happens to contract.

?Only two species of Plasmodium cause the dreaded relapses of the disease,? said Riehle. ?One of them, Plasmodium vivax, can lie dormant in the liver for 10 to 15 years, but now drugs have become available that target the parasites in the liver as well as those in the blood cells.?

That said, there are no effective or approved malaria vaccines. A few vaccine candidates have gone to clinical trials but they were shown to either be ineffective or provide only short-term protection. If an effective vaccine were to be developed, distribution would be a major problem, Riehle said.

Researchers and health officials put higher hopes into eradication programs, which aim at the disease-transmitting mosquitoes rather than the pathogens that cause it.

?The question is ?What can we do to turn a good vector into a bad vector??? Riehle said.

?The eradication scenario requires three things: A gene that disrupts the development of the parasite inside the mosquito, a genetic technique to bring that gene into the mosquito genome and a mechanism that gives the modified mosquito an edge over the natural populations so they can displace them over time.?

?The third requirement is going to be the most difficult of the three to realize,? he added, which is why his team decided to tackle the other two first.

?It was known that the Akt enzyme is involved in the mosquito?s growth rate and immune response, among other things,? Riehle said. ?So we went ahead with this genetic construct to see if we can ramp up Akt function and help the insects? immune system fight off the malaria parasite.?

The second rationale behind this approach was to use Akt signaling to stunt the mosquitoes? growth and cut down on its lifespan.

?In the wild, a mosquito lives for an average of two weeks,? Riehle explained. ?Only the oldest mosquitoes are able to transmit the parasite. If we can reduce the lifespan of the mosquitoes, we can reduce the number of infections.?

His research team discovered that mosquitoes carrying two copies of the altered gene had lost their ability to act as malaria vectors altogether.

?In that group of mosquitoes, not a single Plasmodium oocyst managed to form.?

At this point, the modified mosquitoes exist in a highly secured lab environment with no chance of escape. Once researchers find a way to replace wild mosquito populations with lab-bred ones, breakthroughs like the one achieved by Riehle?s group could pave the way toward a world in which malaria is all but history.

This study was funded by the National Institutes of Health.




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