Monday, 27 August 2012

Genetically-engineered Mosquitoes

Genetically-engineered Mosquitoes Can’t Transmit Malaria
Scientists at the University of California at Irvine and and the Pasteur Institute in Paris say they’ve used genetic engineering to create mosquitoes that can’t infect people with malaria. They used Anopheles stephensi mosquito — a major source of malaria in India and the Middle East — but say the technique could be used on dozens of different types of mosquitoes. Malaria parasites picked up by these mosquitoes are killed by the the mosquitoes’ immune systems. So the insects can’t transmit malaria through their bites. The scientists made their announcement on June 17, 2012, and their paper was published in the Proceedings for the National Academy of Sciences. Scientists have genetically altered the Anopheles stephensi mosquito so that their immunes systems kill the malaria parasite. They say their technique could be used with dozens of different types of mosquitoes.
More than 40 percent of the world’s population lives in areas where there is a risk of contracting malaria. The World Health Organization says there were about 216 million cases of malaria and an estimated 655,000 deaths in 2010. The deaths are largely infants, young children and pregnant women. Most deaths occur among children living in Africa where a child dies every minute from malaria.
Anthony James of UC Irvine said:
Our group has made significant advances with the creation of transgenic mosquitoes But this is the first model of a malaria vector with a genetic modification that can potentially exist in wild populations and be transferred through generations without affecting their fitness.
I did not talk to these scientists, and I have questions. What happens to the mosquitoes already in the wild, which carry the malaria parasite? Do they breed with the genetically modified mosquitoes so that some inherit malaria-killing immune systems? There will be another question for some. Is it wise to release genetically modified mosquitoes into the wild? For the families of children who might die of malaria, the answer is clear: pursue this promising line of research. The rest of us will need to acknowledge that we live in a world where the questions themselves are getting tougher.
Bottom line: Scientists at the University of California at Irvine and and the Pasteur Institute in Paris have used genetic engineering to create mosquitoes whose immune systems kill the malaria parasite. These mosquitoes, then, can’t transmit malaria.
Transgenic Anopheles stephensi coexpressing single-chain antibodies resist Plasmodium falciparum development
Anopheles stephensi mosquitoes expressing m1C3, m4B7, or m2A10 single-chain antibodies (scFvs) have significantly lower levels of infection compared to controls when challenged with Plasmodium falciparum, a human malaria pathogen. These scFvs are derived from antibodies specific to a parasite chitinase, the 25 kDa protein and the circumsporozoite protein, respectively. Transgenes comprising m2A10 in combination with either m1C3 or m4B7 were inserted into previously-characterized mosquito chromosomal “docking” sites using site-specific recombination. Transgene expression was evaluated at four different genomic locations and a docking site that permitted tissue- and sex-specific expression was researched further. Fitness studies of docking site and dual scFv transgene strains detected only one significant fitness cost: adult docking-site males displayed a late-onset reduction in survival. The m4B7/m2A10 mosquitoes challenged with P. falciparum had few or no sporozoites, the parasite stage infective to humans, in three of four experiments. No sporozoites were detected in m1C3/m2A10 mosquitoes in challenge experiments when both genes were induced at developmentally relevant times. These studies support the conclusion that expression of a single copy of a dual scFv transgene can completely inhibit parasite development without imposing a fitness cost on the mosquito.

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