Can CRISPR Tackle Zika?

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Can genetic modification aid us in fighting mosquito-borne diseases?

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a relatively new biotechnology that allows the user to target specific genetic codes within DNA and edit them, working like a pair of DNA scissors with a copy & paste button. CRISPR is easier and cheaper than previous gene editing technologies and has been highly regarded as a breakthrough tool for correcting genetic conditions and even infectious diseases through gene drive. Whether it be the latest announcement that CRISPR reversed Huntington’s Disease in mice or that it could provide rapid diagnostic improvements, the technology is being considered a breakthrough for many diseases and conditions, including vector-borne diseases.

By harnessing the power of gene drive, CRISPR could ensure that edited genes are passed down through all generations. Harnessing the power of gene drive means that instead of 50% of offspring getting a gene passed down (the natural process), and researchers can ensure that all offspring inherit the altered gene. In short, harnessing the gene drive gives us the capability to make sure that a specific gene is passed down through all generations of an organism.

This ability has caused increasing attention on the potential for CRISPR to be use as a tool against vector-borne diseases, specifically those that are spread through mosquitoes, such as Zika, malaria, and Dengue.

In fact, molecular biologist Nina Fedoroff, PhD recently gave a TED talk about the potential for CRISPR to be used to combat the Zika virus, and highlighted how the social implications of labeling of genetically modified organisms (GMOs) could impact its use. Dr Federoff addressed those concerns in her talk, and highlighted the safety of GMO mosquitoes and the benefits of using biological control over other methods.

Dr Federoff discussed the history and symptoms of the Zika virus, highlighting the role of travel and globalization in its spread. She stated that current control efforts for Zika are limited—a vaccine does not yet exist and mosquito-repellent is only as effective as the diligence of the user. In addition, large-scale insecticide spraying efforts can be difficult because of concerns over toxicity, etc.

This then begs the question: What is more effective than spraying but does not involve toxic exposure?

Dr Federoff pointed to the release of GMO mosquitoes in Brazil, which resulted in a year over year decrease of Dengue cases by 91%. This approach involved releasing thousands of modified male Aedes aegypti (the urban mosquito that is the culprit for most Zika, Dengue, and malaria cases), that contained a lethal gene the mosquito could pass to their offspring, which would prevent them from fully developing. This tactic is different than previous methods that intentionally infect the mosquitoes with Wolbachia pipientis bacterium, which are harmless to humans but prevent the mosquitoes from Zika, Dengue, and Chikungunya infections, meaning that they cannot spread them. In the case of the gene-editing method Dr Federoff discussed in her presentation, a kill-switch is genetically imbedded in the male mosquito, so that when it mates, its offspring would receive the kill-switch that prevents them from fully developing, and thus transmitting disease.

Despite its success, Dr Federoff mentioned that because of the strong aversion Americans have against GMO’s—including strict regulations (overseen by the US Food and Drug Administration (FDA), US Environmental Protection Agency, and US Department of Agriculture)—many individuals in the United States voiced concerns regarding the testing of these mosquitoes here. After 2 years, the FDA was elected to be the responsible group for regulating these GMO mosquitoes, which they determined to be a “new animal drug”.

Following the review, the FDA opted for a small test of the GMO mosquitoes in the Florida Keys; however, despite education efforts and years of review regarding the safety of these mosquitoes, there was a substantial public uproar regarding the field test, which resulted in a referendum. The public outcry led to a split among voters in Key Haven, Florida (the site for the field test), which made it more challenging to move forward, as the referendum results were nonbinding. Indeed, despite FDA approval, there is still substantial pushback from residents, which highlights the almost instinctual aversion humans have for genetically-modified biological control methods.

Still, Dr Federoff emphasized that previous mosquito control efforts, such spraying, are laborious, moderately effective, and potentially environmentally toxic. She noted that “biological control of harmful insects can be both more effective and very much more environmentally friendly than using insecticides, which are toxic chemicals.” Concluding her talk with a plea to the audience, Dr Federoff emphasized the need to dig past misinformation and hype to truly look at the science of this work and the substantial benefits that can come from biological control efforts and the science of genetic modification.

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