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Genetically engineered mosquitoes pass lethal gene to offspring

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  • Scientists carry out ‘positive’ trial on Cayman Islands
  • New breed of insect could be used to tackle malaria and dengue fever
  • But critics say it could lead to public health problems

Breakthrough or danger? A UK-based research team has found a way of genetically modifying the Aedes aegypti mosquito so they pass on a deadly gene to their offspring

Breakthrough or danger? A UK-based research team has found a way of genetically modifying the Aedes aegypti mosquito so they pass on a deadly gene to their offspring

Serious concerns have been raised over the release of a new breed of disease-fighting mosquito which has been genetically engineered to kill their own offspring.

There are hopes the project could be used to control agricultural pests and tackle deadly insect-borne illnesses such as dengue fever and malaria.

But the research has raised concerns about the possible side-effects on public health and the environment because, once released, the mosquitos cannot be recalled.

A UK-based scientific team revealed there had been positive signs from the first release into the environment of the mosquitoes, which are engineered to pass a lethal gene onto their offspring, killing them before adulthood.

The study team – which includes experts from Imperial College London and the Liverpool School of Tropical Medicine – released batches of modified mosquitoes in an area of the Cayman Islands where the dengue virus-carrying Aedes aegypti mosquito is common.

The study, published in Nature Biotechnology journal, looked at how successfully the lab-reared, genetically modified insects could mate.

About 19,000 mosquitoes engineered in a lab were released over four weeks in 2009 in a 25-acre area on Grand Cayman island.

Based on data from traps, the genetically engineered males accounted for 16per cent of the overall male population in the test zone, and the lethal gene was found in almost 10 percent of larvae.

Those figures suggest the genetically engineered males were about half as successful in mating as wild ones, a rate sufficient to suppress the population.

Disease fighter? The new breed of mosquitoes could be used to tackle killer illnesses like dengue fever and malaria which affect the world's poorest populations

Disease fighter?  The new breed of mosquitoes could be used to tackle killer illnesses like dengue fever and malaria which affect the world’s poorest populations

Luke Alphey, chief scientific officer at Oxitec, the firm which devised the technique, told the BBC: ‘We were really surprised how well they did.

‘For this method, you just need to get a reasonable proportion of the females to mate with GM males – you’ll never get the males as competitive as the wild ones, but they don’t have to be, they just have to be reasonably good.’

HOW MOSQUITOES KILL THEIR OWN CHILDREN

  • The genetic approach used to create the mosquitoes is a system known as tetracycline-controlled transcriptional activation (tTA).
  • The technique is an extension of one successfully used for decades to control or eradicate pests which involves sterilising millions of insects with radiation.
  • But the process has not worked with mosquitoes, partly because the radiation also injures them, making it difficult for them to compete with healthy counterparts for mates.
  • So Oxitec has now created the Aedes aegypti mosquitoes with a gene that will kill them unless they are given the common antibiotic tetracycline.
  • With tetracycline provided in the lab, the mosquitoes can be bred for generations and multiplied.
  • Males are then released into the wild, where tetracycline is not available.
  • They live long enough to mate but their progeny will die before adulthood.

 

Authorities in the Florida Keys hope to carry out an open-air test on the modified insects as early as December after experiencing the region’s first cases of dengue fever in decades.

Dr Alphey said the technique was safe because only males were released as it was only the females that bite people and spread the disease.

But critics say the process is by no means foolproof.

Alfred Handler, a geneticist at the Agriculture Department in Gainesville, Florida, said the mosquitoes can evolve resistance to the lethal gene while being bred for generations in a lab.

Todd Shelly, an entomologist for the Agriculture Department in Hawaii, also said in a commentary published on Sunday by Nature Biotechnology that 3.5per cent of the insects in a lab test survived to adulthood despite presumably carrying the lethal gene.

Also, the sorting of male and female mosquitoes, which is done by hand, can result in up to 0.5per cent of the released insects being female, the commentary said.

If millions of mosquitoes were released, even that small percentage of females could lead to a temporary increase in disease spread, it was reported by the New York Times.

Oxitec and a molecular biologist, Anthony A. James of the University of California, Irvine, say they have developed a solution — a genetic modification that makes female mosquitoes, but not males, unable to fly.

The grounded females cannot mate or bite people, and separating males from females before release would be easier.

The World Health Organisation expects to release guidance on how GM insects should be deployed in developing countries by the end of the year.

 

Via DailyMail

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HIV discovery brings vaccine closer

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HIV virusAn investigation into the activity of antibodies in HIV patients has revealed that the HIV virus can mutate in order to ‘escape’ this immune response.

Human ADCC (antibody-dependent cell-mediated cytotoxicity) antibodies – which are often present in high concentrations in HIV-infected patients – have been strongly implicated in the protection from HIV in several vaccine trials.

However, we still do not how these antibodies really work, and researchers hope that a better understanding of their processes could lead to HIV treatments that work by boosting the antibodies’ defences.

“These results show what a slippery customer the HIV virus is, but also shows that these ADCC antibodies are really forcing the virus into changing, in ways that cause it to be weaker,” said lead author Stephen Kent from the University of Melbourne in Australia.

Pinpointing mutation’s location

The term ADCC describes an immune phenomenon whereby antibodies bind to cells infected with a virus. This process activates ‘natural killer cells’ that then attack virus-infected cells.

These natural killer cells destroy infected cells by releasing cytokines, such as interferon-gamma, which are small cell-signalling protein molecules that are secreted by numerous immune system cells and cells in the nervous system.

To investigate further, the researchers analysed blood samples of HIV patients to find where the ADCC antibodies were attacking the virus. They did this by using a staining technique to detect exactly which parts of the virus – that is, which peptide segments – were stimulating the release of cytokines.

Stopping the virus taking hold

The team sequenced the patient’s own virus and found mutations at sites targeted by these ADCC antibodies. Their technique also allowed them to study how the mutations arose over time.

The assay proved additionally valuable because it can be performed on serum or plasma samples, and not cells, which makes for a much easier and less invasive procedure where patients are concerned.

The results, published in Proceedings of the National Academy of Sciencestis month, show that ADCC antibodies force the virus into changing in ways that cause it to be weaker, said Kent.

“They also imply that if good ADCC antibodies were available prior to infection, via a vaccine, we might be able to stop the virus taking hold. This is the holy grail.”

According to co-author Ivan Stratov from the University of Melbourne, “The potential to use ADCC antibodies to kill virus infected cells (rather than just free virions) is a great advance in HIV vaccine research. And harnessing natural killer cells to combat HIV could add great potency to existing vaccine strategies.”

The team is now working on purifying and producing these antibodies in bulk quantities and testing them in a simian (primate) infection model to see if they can prevent infection – by the simian immunodeficiency virus – in monkeys.

Putting pressure on the virus

Over 40 million people around the world have acquired HIV or AIDS, according to the latest toll compiled by the World Health Organisation (WHO) and UNAIDS.

Although the disease was identified over 25 years ago, there is still no vaccine or cure but antiretroviral drugs can be used to manage the condition.

“The work … shows that these types of antibodies are initially quite effective in eliminating virus but eventually they fail because the virus mutates too quickly,” said Marc Pellegrin from the Walter & Eliza Hall Institute of Medical Research in Melbourne, who was not involved in the study.

“The implications … are that our immune system, through these antibodies, is able to exert considerable pressure on the virus to the point where it must mutate to persist and survive. The corollary is that if we can boost this type of response and make it more robust and broad we can better control HIV.”

Via CosmoMag