What's not green and come in cagefuls? Efficient GM mosquitoes

Genetic changes can be introduced into large lab populations over the span of a few generations with just a small number of modified mosquitoes. The technique could be used to create malaria-resistant mosquitoes.

Teams around the world are feverishly working on genetically manipulating mosquitoes to end the spread of malaria.

But their success depends on how well the genetic modification spreads in the wild. What unique advantage must they have to out survive the natural population and control a disease affecting 300 million people a year?

Scientists are working on several strategies, ScienceNOW explains:

Many involve so-called selfish genes, strange stretches of naturally occurring DNA that have ways of spreading through populations in almost parasitic fashion. The idea is that these genes could be hitched to others that mess with the parasite's life cycle and make those spread as well. But although researchers have had some success in fruit flies, nobody has been able to get a gene drive system going in mosquitoes.

To that end, Andrea Crisanti from Imperial College London and colleagues have discovered a modified genetic element that can efficiently spread through caged populations of Anopheles gambiae (pictured), a key carrier of the malaria parasite, Plasmodium.

The genetic element – a homing endonuclease gene (HEG) called I-SceI – homes to a particular portion of the DNA, where it becomes integrated into the broken chromosome.

The process – a sequence-specific genetic drive – could be used to transmit a genetic manipulation through mosquitoes populations, affecting their ability to be malaria’s vector.

HEG is a selfish gene found in fungi, plants, and bacteria that can create a second copy of itself in individuals that have only one, ensuring all offspring have the gene as well.

  1. They bred a population of Anopheles mosquitoes that glowed in the dark with a green fluorescent gene.
  2. Then they released into their cages small numbers of mosquitoes with an HEG designed specifically to break up the fluorescent gene in sperm cells and insert itself into that same place on the chromosome (to ensure its dissemination into successive generations).
  3. To monitor the spread of HEG, they counted the number of glowing green mosquitoes in each generation.
  • The cages quickly grew darker over time, as the team observed rapid invasion and persistence of I-SceI through several generations of caged mosquitoes.

In fact, if just 1% of the mosquitoes had HEG at the start of the experiment, approximately 60% would 12 generations later.

The next step, Crisanti says, is to make HEG break up a gene crucial for malaria transmission. It could be an odor-recognition gene that helps the mosquito find its host or one that the malaria parasite needs to enter the mosquito's salivary glands. The team already has 10 to 15 candidates.

The study was published in Nature yesterday.

Image: Janice Carr / CDC

This post was originally published on Smartplanet.com