Over five million people worldwide die from vector-borne diseases every year. Vector-borne diseases, such as malaria, dengue, and Zika, are pathogens that can be transmitted through the bite of an insect. Though vaccines for some of these illnesses are in development, current prevention options are very effective.
To address this issue, the Defense Advanced Research Projects Agency (DARPA) is looking at synthetic biology as a method to find an easy to use, cost-effective solution.
In a recent announcement, DARPA awarded Ginkgo Bioworks, Azitra, Latham BioPharm Group, and Florida International University (FIU) a contract of up to $15 million to create a novel, long-lasting mosquito repellent using engineered microbes. This partnership is a part of DARPA’s ReVector program that supports groundbreaking technologies to protect US troops from mosquito-borne illnesses.
A Military Upgrade For Bug Spray
This map shows how many of the 6 most common vector-borne diseases could potentially affect populations in 5 square kilometers sections. Tropical regions like South Africa, Western Sub-Saharan Africa, and Southeast Asia are particularly vulnerable. RESEARCHGATE
Infections like malaria are not commonplace in temperate regions like the United States. High mosquito populations—and therefore higher instances of disease—are more common in tropical and subtropical regions. However, many US troops operate in these hotbed locations, hence DARPA’s motivation for the project.
Currently, all available mosquito repellents fall short in providing long-lasting, effective protection. They require an application to the skin every few hours and are impractical for use in the field. ReVector’s new project hopes their microbe-based solution will protect against mosquito bites for at least two weeks, skipping the need for continuous reapplication.
Why Choose Synthetic Biology?
As a field, synthetic biology is well placed to develop a novel, bio-based approach to disease prevention. One of the biggest sectors of biotech innovation is microbe engineering. By modifying a microbe’s tiny cellular factories, research teams can genetically engineer organisms to produce a wide range of materials. Using computing and big data, synthetic biologists can rapidly prototype and iterate on different solutions to produce the desired molecule.
Ginkgo Bioworks will take the lead as the primary contractor for the project. Ginkgo is well known in the synthetic biology industry and beyond for providing biotech infrastructure as a service—similar to Amazon Web Services but for biology. Rather than producing the final products itself, Ginkgo designs and engineers microbes for a wide range of customer needs. For this project, Ginkgo will leverage their organism foundries—the company’s automated platforms for microbe design and validation—to engineer microorganisms found on human skin.
Unlocking the Skin Microbiome
The human skin microbiome is a diverse neighborhood of microorganisms that protect against dermatological diseases. Each microorganism occupies a wide range of skin niches and plays a specific role in educating the billions of skin cells on how to respond to pathogenic outsiders.
Zach Smith, Director of Government Business at Ginkgo Bioworks, gave insights into the project’s approach. “There are two ways to deal with mosquitoes, you can repel them or you can isolate the signals humans give off to attract mosquitoes and weaken them. We are planning to do both,” says Smith.
Using high throughput testing, Ginkgo aims to rapidly discover the best combination of engineered microbial compounds to produce a Live Biotherapeutic Product (LBP). But, even with an LBP, humans still naturally produce byproducts that attract insects.
Humans give off heat, carbon dioxide, and certain chemical elements and compounds called volatiles that vaporize rapidly off the skin. If the compounds remain volatile, the repellent would only diminish the number of mosquitoes a person attracts rather than deterring them entirely. However, if these volatile compounds can be identified, the project team could produce a repellent with additional properties that prevent these compounds from vaporizing in the first place.
A Fullstack Partnership
In the initial research phase of the project, Ginkgo plans to collaborate with top mosquito researcher and neurogeneticist Matthew DeGennaro, Ph.D., of FIU’s Biomolecular Sciences Institute. As an expert in molecular genetics and the odor attraction profile of mosquitoes, DeGennaro can provide unique insights into the molecular compounds needed to repel mosquitoes long-term.
Though popular products like DEET are considered effective, mosquito repellent technology hasn’t been updated in decades. “DEET has been the gold standard for mosquito repellency since the 1940s. Over the past 80 years, [the science community] has learned so much more about how mosquitoes find their hosts,” said DeGennaro in a press release. For Ginkgo, understanding the complex relationship between humans and mosquitoes at the microbial level will be key to the company’s bioengineering process.
As the research progresses, Azitra, a clinical-stage medical dermatology company, will leverage its extensive scientific knowledge of the skin microbiome to develop and characterize various bacterial strains. To ensure the whole project runs smoothly from beginning to end, Latham BioPharm Group will provide extensive program management, systems integration support, and regulatory strategy expertise.
Project Validation: Testing, Testing, 1,2, 3
The project is a four-year effort organized into three key phases. First, the team will work to produce and test as many potential repellents as possible. Ginkgo will take whichever repellents show the most promising results and produce more microbe variations until they identify a select few microbe strains with the strongest repellent properties.
Additionally, some microbes that may be less effective in repelling mosquitoes may be better at masking volatiles. Understanding the different properties of the microbes will be essential in engineering a final product. Once this microbial cohort is identified, the team will begin community modeling of the skin to ensure the microbe strains can persist symbiotically on the skin for at least two weeks.
Finally, when the best microbes are identified and verified for safety, human participants will apply the repellent onto their arms and stick them into a container of mosquitoes. If the mosquitoes aren’t attracted to the human skin, the repellent will be doing its job. Though it sounds deeply unpleasant for the human participants, it’s also an easy, low-tech way to ‘field test’ the product.
Looking Beyond Mosquitoes: A New Approach To Skin Protection?
If the team can develop a suitable repellent, the applications could have significant, far-reaching benefits. Jason Kelly, Ginkgo Co-founder, and CEO summed up the technology’s potential in a recent press release. “The ability to program living cells that are part of our natural microbiome, and thus improve our ability to fight off challenges like mosquito vectoring of disease, has enormous potential in global health. Our research in collaboration with Azitra, FIU, and LBG could be transformative to the next generation of living medicine.”
The protocols and lessons learned from this project could produce a genetic toolkit for leveraging the skin microbiome against other vector-borne diseases. Though the COVID-19 pandemic isn’t a mosquito-transmitted illness, the importance of preventing animal-to-human pathogens is painfully clear. If successful, ReVector’s synthetic biology initiative could blaze a trail for other biotherapeutics.
For Ginkgo’s Zach Smith, the applications for microbiome technology aren’t necessarily limited to disease prevention. Smith is especially interested in bioengineered sunblock. “We don’t know if it is possible, but if it is a [sun] repellent that lasts a day, it would be a game-changer for me and my skin,” says Smith.
The potential of leveraging skin microbes against disease and damage is only just beginning to be explored. Even if the project avoids setbacks, it will be years before this technology reaches the military. And it will likely be even longer before civilian populations benefit, if they do at all. ReVector’s project also does not indicate whether or not the end product could become available in developing countries where robust mosquito repellents are sorely needed.
But the partnership also demonstrates how far synthetic biology has grown as an industry. This is not the field’s first partnership with DARPA. But the broad coalition of biotech companies and experts is a promising marker of growth in the bioeconomy. Though it’s too early to hang any hats on, this new venture could represent a milestone for both synthetic biology and the long-enduring fight against some of our world’s most deadly pathogens.
I’m the founder of SynBioBeta, and some of the companies that I write about are sponsors of the SynBioBeta conference and weekly digest, including Ginkgo Bioworks. I’m also an Operating Partner at DCVC which is an investor in Ginkgo Bioworks. Thank you to Vinit Parekh for additional research and reporting in this article.