Disease-fighters disrupt mosquito's genes with molecular scissors

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:


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.

Discuss this post

Gloria Becksvia FacebookDeleted

We already have genetically modified (GM) corn and now we will have GM mosquitoes. What's next, GM humans?

What do they plan to do with GM mosquitoes any way, BREED them and release them into the wild for field testing? Just what we need more mosquitoes.

    Reply#2 - Fri Mar 22, 2013 6:06 AM EDT

    You're kidding right? Did you read the article?

    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.

    To break it down for you, they want to prevent virus transmission to humans from mosquitoes.

    • 10 votes
    #2.1 - Fri Mar 22, 2013 8:15 AM EDT

    What's next, GM humans?

    I certainly hope so. If I ever have kids, I want them to be next-generation, disease-free superhumans with twice our natural lifespan, brain power, and no chance of genetic disease. Take THAT Mother Nature!

    • 5 votes
    #2.2 - Fri Mar 22, 2013 1:18 PM EDT

    S&W 45

    We already have genetically modified (GM) corn and now we will have GM mosquitoes. What's next, GM humans?

    CHINA IS ENGINEERING GENIUS BABIES

      #2.3 - Sat Mar 23, 2013 2:26 AM EDT
      Reply

      Sounds really cool... but say they find the disease transmitting genes. How do they snip it from the gazillions of mosquito already in the wild?

        Reply#3 - Fri Mar 22, 2013 8:52 AM EDT

        You don't snip the ones in the wild. You modify some in the lab, breed them and release them in the wild. Repeat as necessary. This may not totally eliminate dengue-carrying mosquitoes, but it could severely cut down that population.

        • 6 votes
        #3.1 - Fri Mar 22, 2013 10:13 AM EDT
        Reply

        Here in Key West, the Mosquito Board wanted to release GM mosquitoes to reduce the Aedis Egypti population. Bascially they are supposed to be sterile males that will breed with the biting females. Therefore less mosquitoes because of the sterility of the males, fewer eggs, etc. We are still arguing about it. Yes, we had a dengue outbreak a few years back, but have not seen one since. You would think it would be a simple matter to agree to this, especially since the same experiment was done in the Cayman's with success. But the Commission wants approval from some other authority before approving. There is still some fear of GM mosquitoes passing their modification to humans through a bite. Well male mosquitoes do not bite. And what kind of modification would the bugs pass? They are sterilized. Talk about small minds. Anyway, let the entimologists develop this GM mosquito. Getting people to accept it is another story. I wish them luck. Doing this research could go a long way to eliminating diseases which are spread by mosquitoes all over the world.

        • 2 votes
        Reply#4 - Fri Mar 22, 2013 10:23 AM EDT

        "Genetically Modified" is a dirty word to some people; they hear it and they react negatively without hearing or caring about the details. It doesn't help that the media comes up with colorful titles for genetically modified food products like "franken food" that conjure images of silly, grotesque experiments by mad scientists.

        The only way it's going to change is by forcing these products (or insects, in this case) through the government's silly regulations and getting it out there. Once nothing bad happens, people will lose interest in complaining about it actively and move on to the next big scare.

        • 3 votes
        #4.1 - Fri Mar 22, 2013 1:25 PM EDT

        In this case it appears they ARE wishing to introduce this into the wild breeding population. I'm not against trying to reduce or prevent disease transmission. I'm NOT a franken-alarmist. However, I do worry about us introducing things into the wild when we don't fully understand the ramifications of what we have adjusted - even if we think we do. What if that gene also has another function that we haven't quite found yet? Remember when it was announced that we had fully mapped the human genome and understood how to "build" a human? Immediately cloning became a hot topic. Then later it was found out that the mapping we did was only a FRACTION of what was actually there. Humans have a bad habit of being a bit arrogant and shooting before they know what they are aiming at. Remember all of the introduced species that were supposed to take are of other introduced species - only to have the cure be as bad as the sickness? Remember Africanized honey bees? It's OK, we're being careful and there's supposedly no way they'll escape, right? I'm just saying we need to be humble and take so much care in doing this stuff. Once you let the genie out of the bottle there's often no stuffing it back inside.

        • 1 vote
        #4.2 - Fri Mar 22, 2013 2:20 PM EDT

        We need to modified scientist's gene so they don't have to think that hard. Let's see what they think about their new self.

          #4.3 - Fri Mar 22, 2013 2:25 PM EDT

          Problem is that mosquitoes are part of the ecosystem. Fewer mosquitoes, and you are going to have consequences that we don't understand at this point.

          This research is far more interesting - breed mosquitoes that are resistant to human diseases. You won't reduce their number, and their bites will still itch, but we won't get sick from them. Even more interesting is to turn mosquitoes into vaccine-delivery mechanisms, especially useful in geographically remote areas.

          Just because GM is a dirty word to some non-scientific people doesn't mean that it is a perfect solution to all problems. For example, if you breed a plant that is resistant to certain pesticides, and then start spraying thousands of acres with pesticide, that works greet till the pests breed resistance and you are back where you started.

          Anti-scientists have used poor GM science to condemn the whole GM field, but their lack of understanding doesn't excuse the problems.

          • 1 vote
          #4.4 - Fri Mar 22, 2013 2:37 PM EDT

          However, I do worry about us introducing things into the wild when we don't fully understand the ramifications of what we have adjusted - even if we think we do.

          So your argument boils down to "what if something unexpected happens?" Which can be applied to any human endeavor, anywhere. Genetic modification is not a new thing; GM crops have been used without disastrous, wild mutations, massive, uncontrolled spreading of the crop, or any other catastrophe that paranoid anti-GM people might imagine.

          As evidence for your claim you cite past mistakes and previous discoveries when people had thought that "all the science was done". And I can assure you, the scientists are looking at those too, because we learn as much or even more from our mistakes as we do our successes. If the scientists THINK they have all the angles covered, but they're wrong, how will anybody know until they go ahead and try? Listening to non-scientists quote movies and wildly speculate on things that can't happen (mosquitoes implanting genes into humans?) isn't helpful, and blind fear is never a good reason to halt scientific progress.

          Yeah, sometimes mistakes happen and that genie does get loose. After it happens all we can do is figure out what went wrong and try again. The only solution to bad science is good science.

          Just because GM is a dirty word to some non-scientific people doesn't mean that it is a perfect solution to all problems.

          It doesn't have to be a perfect solution, and nobody's claiming that it is. But as a solution, it can only get better if people overcome their irrational fear of it and make it available as a tool.

          • 2 votes
          #4.5 - Fri Mar 22, 2013 2:40 PM EDT

          It doesn't have to be a perfect solution, and nobody's claiming that it is.

          I disagree. There HAVE been people, some of them allegedly scientists, who have claimed that GM is the perfect solution.

          But as a solution, it can only get better if people overcome their irrational fear of it and make it available as a tool.

          The reason for the irrational fear is as a reaction the irrational claims. Non-scientists need to understand science better; at the same time, scientists need to remember who they are and not act as salespeople.

            #4.6 - Fri Mar 22, 2013 3:35 PM EDT

            I didn't get into this in the story, because I'm not sure whether this is actually the case, regulatory-wise ... But Adelman's view is that these mosquitoes would not face such a high bar for genetic modification because technically, the genes are not modified ... in the sense of adding genetic code. Rather, the relevant genes would be permanently disrupted by subtraction. It's as if you took a little snippers and snipped some essential coding from the genes of each mosquito. Right now that's just a theoretical case, because researchers haven't identified the target code to block virus transmission. But I wonder if that makes any difference in the discussion over TALEN genetic engineering...

              #4.7 - Fri Mar 22, 2013 4:57 PM EDT

              This is an interesting idea, but I have trouble understanding its utility from a practical standpoint. There's overwhelmingly more mosquitoes out there than we can possibly release. How could we ensure that the deletion is a dominant characteristic and spreads through the population?

                #4.8 - Fri Mar 22, 2013 5:32 PM EDT

                I disagree. There HAVE been people, some of them allegedly scientists, who have claimed that GM is the perfect solution.

                Okay... and they're probably wrong? I mean, as far as I know, we don't have the resources to genetically modify everything perfectly or on a big enough scale to foment all the changes we want in a given environment. You mentioned yourself that there are so many mosquitoes that we can't possibly expect to change the entire population with our own modified additions. I don't see anyone claiming genetic modification is a silver bullet to solve X problems, but if you do, fine, they're probably mistaken. I guess I don't understand how that's a justification for the irrational fears, though. There are less ambitious and significant GM products that are likewise shunned and demonized by anti-GM people, and I don't see how making bigger crops with less water or salmon with less food is an irrational claim.

                It's unfortunate that scientists need to act like salespeople, but that's a result of the era we live in, where people take a greater interest in things that might seem arcane or irrelevant to them. It's only natural that scientific endeavors that have an impact on the environment and markets should come under public scrutiny, and I'm not sure how the scientists are supposed to defend their work if not by acting as salespeople.

                  #4.9 - Fri Mar 22, 2013 10:07 PM EDT
                  Reply

                  This will not end well.

                  • 1 vote
                  Reply#5 - Fri Mar 22, 2013 11:33 AM EDT

                  lol, giant Godzilla-sized mosquitos, good or bad? Discuss

                    #5.1 - Fri Mar 22, 2013 12:32 PM EDT

                    I would say good. Then maybe they would thin out the human herd a bit. We could even off up some of societies less desirables as sacrafices.

                    • 1 vote
                    #5.2 - Fri Mar 22, 2013 12:49 PM EDT

                    I too, would welcome our new blood-sucking overlords!

                    • 3 votes
                    #5.3 - Fri Mar 22, 2013 1:03 PM EDT

                    I'll bet this is how the Zerg started.

                    FOR THE SWARM!!

                    (Seriously though, it probably will end well)

                    • 4 votes
                    #5.4 - Fri Mar 22, 2013 1:27 PM EDT

                    Good thing. Then the little bastards can't sneak up on me! Face me like a man you buzzy little beast!

                    • 1 vote
                    #5.5 - Fri Mar 22, 2013 4:18 PM EDT

                    Did any of you get the memo directing you to the vaccination for the new diseases that will be created by these critters? I didn't think so.

                    "We need to immunize to help reduce population." Bill Gates.

                      #5.6 - Sat Mar 23, 2013 5:35 AM EDT
                      Reply

                      How about a gene that makes them hate human blood.

                        Reply#6 - Fri Mar 22, 2013 3:59 PM EDT

                        That would be a very interesting project, but it would probably be unsuccessful in the wild. The mosquitoes that weren't modified would have a distinct evolutionary advantage, since they'd have access to a food source that the GM mosquitoes don't. That would probably ensure that the GM mosquitoes would be out-bred by their rivals, and render the entire operation useless.

                        In order to allow the GM mosquitoes to infiltrate the population and spread the genetic mod successfully, the modification needs to either give them a survival advantage or at least be neutral in that respect. That's probably why the scientists are trying to render the mosquito resistant to the diseases we get from them, rather than trying to keep them from biting humans altogether.

                        • 1 vote
                        #6.1 - Fri Mar 22, 2013 10:13 PM EDT
                        Reply
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