Zika, dengue fever and other mosquito-born illnesses have surged to public attention in recent years, with Zika afflicting thousands of people across the Americas. The Zika outbreak that began in 2015 resulted in 1,835 babies born in Brazil with abnormal brain development or problems with their central nervous systems, according to the World Health Organization. Worldwide, another 3.2 million cases of dengue fever, which causes high fever and vomiting, were reported in 2016, according to the WHO.
University of California researchers are tackling the problem by working to develop genetic defenses against mosquito-borne diseases. The team, led by UC Riverside researcher Omar Akbari, recently received a four-year grant from the federal Defense Advanced Research Projects Agency totaling $14.9 million.
Scientists across six UC campuses hope to develop a technique called “gene drives” and monitor their spread over more than 20 generations of mosquitoes in the laboratory. Here, Akbari discusses gene drives and the impact that the team hopes to make.
Q. What are gene drives and how do they work?
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A. Gene drive is a technique that can be used to promote the inheritance of a particular gene to increase its prevalence in a population. During normal sexual reproduction, we have two versions of a gene, and each of those has a 50 percent chance of being inherited by the offspring. Gene drives can circumvent those rules and increase the odds by which the drive is actually passed on to the offspring. This can allow them to spread really quickly in a population, and as they spread, they can be used to either completely replace a population with a desired gene, or they can suppress a population and potentially eradicate a species completely.
Q. How will you be testing them?
A. We’ll be testing them strictly in the laboratory. … We’ll create transgenic mosquitoes and test their ability to bias inheritance or drive into a laboratory population. So we’ll track over a number of generations and see how well they spread. And parallel to that, in addition to developing the gene drive, we’re also developing the mechanisms to reverse them. So as we learn more about how drives can behave in a population and spread, we can also do experiments where we do reversals of them and block the spread in the population.
Q. What kinds of gene drives will you be testing?
A. One type of gene drive we plan to develop is a population suppression type drive, where as the drive spreads into a population, once it fixes, the population becomes unstable and crashes. To do that, we’re going to target genes that are important for female fertility. Once the gene drive fixes, all females are homozygous for the drive, and when that happens, they’re all sterile. And if all females are sterile, the males won’t have anyone to mate with, and the population will crash. … We have other kinds of gene drives that spread into a population, and the goal of those is that they persist. … We designed them to link to effector genes, (like) a gene that can disperse pathogen resistance to dengue fever. You can link those genes to the gene drive system and use the gene drive to spread the anti-dengue gene into the population, and then individuals that have the gene drive can no longer vector that pathogen.
Q. What do we already know about gene drives and what don’t we know?
A. We know that we can design them in the laboratory and bias transmissions in a small number of generations, but we don’t understand how we can design a gene drive that will be evolutionarily stable enough to persist in a population long-term. … One of the big problems right now with gene drives is resistance. As we test these drives in laboratory populations, they become resistant to the mechanism really quickly. … The other thing we don’t understand is something we’re not going to get into with our grant, but it’s how well a gene drive would actually function in a diverse population. In the wild, populations are extremely diverse, but they’re not very diverse (in the lab). They’re strains that have been maintained for long periods of time, so we may be able to get gene drives to work out in the lab, but will they actually work in diverse populations?
Q. Why does your research focus on mosquitoes?
A. Mosquitoes spread diseases, so if we can come up with better ways to control the spread of pathogens via mosquitoes, then potentially, we could have solutions to some of those problems. We want to know how effective the gene drive might be at functioning in the mosquito genome. That’s why we’re focused on mosquitoes, but really, the goal of this DARPA effort is to understand how well gene drives work and how to defend against them in case … we want to remove a gene drive from the population.
Q. What are current methods of controlling mosquito populations?
A. The number one way to control mosquito populations is pesticides. … You can (also) use bed nets or traps, but the bottom line is if you really look at the numbers, the number of people that are dying of mosquito-borne diseases is enormous. With malaria, there’s over a million deaths per year … so the current measures are just not effective enough. I don’t think gene drives are going to be the silver bullet, but they could be combined with all these other control measures to actually have a long-lasting impact.