‘Genetically modified mosquitoes could eradicate malaria’

A strain of genetically modified mosquitoes could be the key to wiping out malaria, scientists have revealed.
Using a groundbreaking gene-editing technique, they have created a mosquito capable of rapidly introducing malaria-blocking genes into the insect population.

And, through its offspring, the strain is ultimately able to eliminate the insects’ ability to transmit the disease to humans.

The new model marks a notable advance in the fight against the disease, experts have said.
The theory is that the genetically modified insects could be released into the wild, where they will breed with malaria-carrying mosquitoes, passing on the gene preventing malaria transmission being passed to their offspring.

With further development the team of scientists at the University of California believe they will be able to establish an anti-malarial mosquito population, that could help eradicate the disease, which sickens millions across the world each year.
To create the new breed, researchers inserted a DNA element into the germ line of Anopheles stephensi mosquitoes.
It resulted in the gene preventing malaria transmission being passed on to an astonishing 99.5 per cent of offspring.

The study appears in the early online edition of Proceedings of the National Academy of Sciences.
Prof. Anthony James, of molecular biology and biochemistry and molecular genetics at University of California Irvine, said: “This is a significant first step. We know the gene works. The mosquitoes we created are not the final brand, but we know this technology allows us to efficiently create large populations.”

Malaria is one of the world’s leading health problems. More than 40 per cent of the world’s population live in areas where there is a risk of contracting the disease.

According to the Centers for Disease Control and Prevention, 300 million to 500 million cases of malaria occur each year, and nearly one million people die of the disease annually – largely infants, young children and pregnant women, most of them in Africa.
Gene drive allows the amplification of a genetic trait so that it becomes prevalent in a specific species or population.

The genes responsible for the drive can be viewed as ‘artificial or synthetic selfish DNA’ systems.
The rules of normal evolution allow for a gene or trait to be passed on through a population when it has a beneficial effect.

Gene drive subverts this by spreading the gene rapidly even if they don’t confer an evolutionary advantage – and, even if they cause some disadvantage.
In general, in sexually reproducing organisms where a parent has two different versions of a gene, each has a 50 per cent chance of being inherited, as each member of the next generation inherits only one copy from each parent.
With drive, this can be increased to up to 100 per cent.

Use of gene drive to modify wild populations was first suggested in 1968 but technology, which would enable realisation of this suggestion is only recently sufficiently advanced.

The study utilised the Crispr method, a gene-editing tool that allows access to a cell’s nucleus to snip DNA to either replace mutated genes or insert new ones.

James said: “This opens up the real promise that this technique can be adapted for eliminating malaria.”
For almost 20 years, Professor James’s lab has focused on engineering anti-disease mosquitoes.
His anti-dengue fever models have been tested in cage trials in Mexico.
And, in 2012, he helped show that antibodies that impair the parasite’s biology adapted from the immune systems of mice can be introduced to mosquitoes.

This trait, though, could only be inherited by about half of the offspring.
Earlier this year, UC San Diego biologists, Ethan Bier and Valentino Gantz, working with fruit flies announced the development of a new method for generating mutations in both copies of a gene.

This mutagenic chain reaction involved using the Crispr-associated Cas9 nucleas enzyme and allowed for transmission of mutations through the germ line with an inheritance rate of 95 per cent.

The two groups collaborated to fuse Professor Bier and Dr Gantz’s method with Professor James’s mosquitoes.
Gantz packaged anti-malaria genes with a Cas9 enzyme, which can cut DNA, and a guide RNA to create a genetic ‘cassette’ that, when injected into a mosquito embryo, targeted a highly specific spot on the germ line DNA, to insert the anti-malaria antibody genes.

To ensure the element carrying the malaria-blocking antibodies had reached the desired DNA site, the researchers included in the cassette a protein that gave the offspring red fluorescence in the eyes.

Almost 100 per cent of offspring – 99.5 per cent – exhibited this trait, which James said is an amazing result for such a system that can change inheritable traits.

He added that further testing will be needed to confirm the efficacy of the antibodies and that this could eventually lead to field studies.
Bier also noted “the ability of this system to carry large genetic payloads should have broad applications to the future use of related Crispr-based active genetic systems.”

The technique used in this study, gene drive technology, is so powerful that it has prompted leading experts to urge caution.
Genetic engineering of plants and animals has long been an area of scientific dispute.
Effects on the specific species, as well as their ecosystem, would need to be carefully examined and monitored.
Some experts are concerned that off-target effects will produce unexpected consequences, which cannot be controlled once they are released into the wild, whether intentionally or not.

Earlier this year, scientists in the United Kingdom (UK), Australia, United States (US) and Japan issued a warning in the journal Science.
They warned that while gene drive technology has “tremendous potential to address global problems in health, agriculture and conservation… their capacity to alter wild populations outside the laboratory demands caution.”

The warning added: “Just as researchers working with self-propagating pathogens must ensure that these agents do not escape to the outside world, scientists working in the laboratory with gene drive constructs are responsible for keeping them confined.”

However, despite the controversy, academics were quick to recognise the potential of the findings.
Professor Anthony Shelton, from Cornell University, who was not involved in the study, said the authors are justified in their optimism.

The results from this paper appear significant and promising. Genetic engineering of insects is usually focused on their reproduction while this study takes a completely different approach to solving a problem by focusing on the ability of insects to transmit a pathogen.
“In theory this technology should work in the field, but further tests are needed and only then will the full potential of this breakthrough be realised for the benefit of humanity.”

Dr. Gregory Lanzaro, of the University of California, Davis, added: ‘Concern that drug and insecticide resistance are eroding recent successes in managing malaria has drawn attention to alternative approaches, including the use of genetically modified mosquitoes.
“This new study marks a significant advance towards the development of this strategy.”

Read more: http://www.dailymail.co.uk/health/article-3330934/Genetically-modified-mosquitoes-eradicate-malaria-passing-genes-stop-spread-killer-disease-offspring.html#ixzz3sOi3QwDr
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