Virginia Tech

Virginia Tech researchers used a gene disruption technique to change the eye color of a mosquito, a critical step toward new strategies for disrupting the transmission of diseases such as dengue fever. The eye colors of these mosquitoes are varied because of cell-to-cell variability in the degree of gene editing.

Scientists at Virginia Tech have disrupted the genes that control eye color in mosquitoes, using a genetic-engineering technique that could also disrupt the transmission of diseases such as dengue fever.

The technique relies on two specially designed proteins that belong to a class known as transcription activator-like effector nucleases, or TALENs. The technique can target DNA at a specific site in an organism's genetic code, so precisely and efficiently that the journal Science has called the molecules "genomic cruise missiles."

Virginia Tech entomologist Zach Adelman prefers a different analogy. "They're basically a very, very fine-tuned pair of scissors," he told NBC News.

TALENs have been used to edit the genomes of animal and human cell cultures, but Adelman said the approach he and his colleagues used on the mosquito genome was different. Rather than trying to modify the function of a gene, the researchers aimed to disable a gene by snipping away at it. In the journal PLOS ONE, they describe how they targeted a gene whose protein product is essential for the production of eye pigment in Aedes aegypti, the mosquito species linked to the transmission of dengue fever.

Genetically engineered TALEN proteins were injected into the germ cells of mosquito embryos early in their development, with the intention of disrupting the coding for eye pigmentation that would be passed down to the next generation. When the targeted mosquitoes gave birth to baby bugs, a large percentage of them had light-colored eyes instead of the typical black eyes. The lack of pigment served as confirmation that the genetic code was wiped out.

The next step is to identify the genetic mechanisms in mosquitoes that play a role in virus transmission. When the right targets are found, the researchers will try to design a different set of molecular scissors to disrupt that genetic code.

Adelman said he's been working on molecular strategies to fight mosquito-borne diseases for a dozen years, and began the TALEN-based project just last May.

"To date, efforts to control dengue transmission through genetics have focused entirely on adding material to the mosquito genome. Ensuring that this added material is expressed properly and consistently has been a challenge," Adelman said in a Virginia Tech news release. "This technology allows us to pursue the same goals, namely, the generation of pathogen-resistant mosquitoes, through subtraction — for example, removing or altering a gene that is critical for pathogen replication."

More about mosquitoes:

• Gene-modified skeeters could stop dengue fever
• Key West waits on dengue mosquito experiment
• WHO: Dengue is fastest-spreading tropical disease

In addition to Adelman, the authors of the PLOS ONE paper, "TALEN-Based Gene Disruption in the Dengue Vector Aedes aegypti," include Azadeh Aryan, Michelle A.E. Anderson and Kevin M. Myles. The work was funded by the National Institutes of Health and the Fralin Life Science Institute at Virginia Tech.

Alan Boyle is NBCNews.com's science editor. Connect with the Cosmic Log community by "liking" the log's Facebook page, following @b0yle on Twitter and adding the Cosmic Log page to your Google+ presence. To keep up with Cosmic Log as well as NBCNews.com's other stories about science and space, sign up for the Tech & Science newsletter, delivered to your email in-box every weekday. You can also check out "The Case for Pluto," my book about the controversial dwarf planet and the search for new worlds.

Rothamsted Research

Disrupting a mosquito's sense of smell can ward off a bug bite.

Researchers say that they’ve found a new class of chemicals that can drive away mosquitoes by disrupting their odor-sensing system — and the first chemical in that class seems to be thousands of times more effective than DEET.

The compound, called VUAA1, was identified thanks to the kind of high-throughput screening process that is more typically used for drug discovery, said Vanderbilt University professor Laurence Zwiebel, a member of the research team. Zwiebel and his colleagues published their findings online this week in the Proceedings of the National Academy of Sciences.

"This compound is really a first-in-class molecule to do this action," Zwiebel told me today.

A mosquito's olfactory system relies on a variety of receptors spread out on the bug's antennae — known odorant receptors, or ORs. The receptors are tuned to respond to different types of odors, including the smell of sweat and blood, and they activate switches called OR co-receptors (Orcos) to tell the mosquito's brain which scent is being picked up.

Researchers screened almost 120,000 small-molecule compounds to check their effects on human embryonic kidney cells that were genetically engineered to include the OR-Orco complexes.  "It was totally a shotgun approach," Zwiebel said. "Throw the kitchen sink at it and see what happens."

The scientists were surprised to find that VUAA1 consistently activated the odor-sensing complexes, even though it's not actually considered an odorant. "It wasn't something we set out to find. It was an anomaly in our tests," another member of the Vanderbilt team, graduate student David Rinker, said in a news release.

"If a compound like VUAA1 can activate every mosquito odorant receptor at once, then it could overwhelm the insect's sense of smell, creating a repellent effect akin to stepping onto an elevator with someone wearing too much perfume, except this would be far worse for the mosquito," said Patrick Jones, a postdoctoral fellow at Vanderbilt who is the study's first author. 

Zwiebel said that he and his colleagues compared the effectiveness of VUAA1 with that of the widely used DEET insect repellant by measuring how much of each compound it took to repel larval mosquitoes in a petri dish. "The more you use, the more the mosquito moves, as if it's trying to get out of Dodge," he explained. A tiny amount of VUAA1 had the same repellent effect as a concentration of DEET that was tens of thousands of times stronger, Zwiebel said.

However, Zwiebel stressed that VUAA1 isn't yet ready for prime time. "The commercialization of this compound has hardly begun," he said. The chemical still has to be fine-tuned and checked for toxicity, and it's possible that other chemicals in the same class will turn out to be more effective or safer. Vanderbilt University says it has filed for a patent on this class of chemicals and is talking with potential corporate licensees about commercialization, with special focus on the development of products to reduce the spread of malaria in the developing world.

Zwiebel noted that VUAA1 has been found to activate the odor-sensing complexes of flies, moths and ants as well. "Basically, every insect that has an olfactory system has this Orco ion channel," he told me. "We have an expectation that every insect will be affected by this molecule. Now, that's both good and bad."

It's good, because the new class of chemicals may yield new ways to drive away other types of nuisance insects and agricultural pests. But it'd be bad if they also drove away beneficial bugs such as bees and butterflies.

"We've all read 'Silent Spring,'" Zwiebel said. "We don't want to have the same DDT story."

More about mosquitoes:

• Scientists tweak mosquito genes to fight malaria
• A malaria mosquito is quickly becoming two species
• Scientists find natural mosquito repellent
• Researchers studying better insect repellents
• U.N.: Efforts on track to halt malaria deaths

In addition to Jones, Rinker and Zwiebel, authors of "Functional Agonism of Insect Odorant Receptor Ion Channels" include Gregory M. Pask. VUAA1 stands for Vanderbilt University Allosteric Agonist 1. The research was supported by the Grand Challenges in Global Health Initiative, funded by the Foundation for the NIH through a grant from the Bill & Melinda Gates Foundation.

Connect with the Cosmic Log community by "liking" the log's Facebook page or following @b0yle on Twitter. You can also check out "The Case for Pluto," Alan's book about the controversial dwarf planet and the search for new worlds.