Can artificial biology make mosquito-borne ailments a factor of the previous?

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Mosquitoes are major vectors of animal-to-human disease transmission. DARPA funded a synthetic … [+] Biology initiative to develop a long-lasting, bio-based mosquito repellent.

Indian Council for Medical Research

Over five million people worldwide die each year from vector-borne diseases. Vector-borne diseases such as malaria, dengue, and zika are pathogens that can be transmitted by an insect bite. Although vaccines against some of these diseases are in development, current prevention options are very effective.

To address this problem, the Defense Advanced Research Projects Agency (DARPA) is studying synthetic biology as a method to find an easy-to-use and inexpensive solution.

In a recent announcement, DARPA Ginkgo Bioworks, Azitra, the Latham BioPharm Group and Florida International University (FIU) placed an order for up to $ 15 million to manufacture a novel, long-lasting mosquito repellent using microbes. This partnership is part of DARPA’s ReVector program, which supports breakthrough technologies to protect US forces from mosquito-borne diseases.

A military upgrade for bug spray

World map with shaded green and blue areas where mosquito-borne diseases are highest

This map shows how many of the 6 most common vector-borne diseases could potentially be affected … [+] Populations in 5 square kilometers. Tropical regions such as South Africa, Western Africa south of the Sahara and Southeast Asia are particularly at risk.

ResearchGate

Infections like malaria are not common in temperate regions like the United States. High mosquito populations – and thus higher cases of disease – are more common in tropical and subtropical regions. However, many US troops operate at these breeding grounds, which is why DARPA is motivated for the project.

At present, all of the mosquito repellants available do not provide permanent and effective protection. They must be applied to the skin every few hours and are inconvenient for on-site use. ReVector’s new project hopes that the microbe-based solution will protect against mosquito bites for at least two weeks, eliminating the need for continuous reapplication.

Why choose synthetic biology?

Synthetic biology is well positioned in this area to develop a novel, bio-based approach to disease prevention. One of the largest sectors of biotech innovation is microbe engineering. By modifying a microbe’s tiny cell factories, research teams can genetically engineer organisms to produce a wide range of materials. Using computers and big data, synthetic biologists can quickly prototype and go through various solutions to make the molecule they want.

Ginkgo Bioworks will lead the project as the prime contractor. Ginkgo is known in the synthetic biology industry and beyond for providing biotech infrastructure as a service – similar to Amazon Web Services, but for biology. Instead of making the end products themselves, Ginkgo designs and constructs microbes for a wide variety of customer requirements. For this project, Ginkgo will use its organism foundries – the company’s automated platforms for the design and validation of microbes – to develop microorganisms found on human skin.

Unlock the skin microbiome

Headshot of young caucasian man wearing glasses and a blue suit looking at the camera.

Zach Smith, Director of Government Business at Ginkgo Bioworks, the leading contractor at DARPA … [+] I drove a program initiative.

Ginkgo Bioworks

The human skin microbiome is a diverse neighborhood of microorganisms that protect against dermatological diseases. Each microorganism occupies a multitude of skin niches and plays a special role in educating billions of skin cells about how to react to pathogenic outsiders.

Zach Smith, Director of Government Business at Ginkgo Bioworks, provided insight into the project’s approach. “There are two ways to deal with mosquitoes: you can fight them off, or you can isolate the signals that people give to attract and weaken mosquitos. We plan to do both, ”says Smith.

With the help of high throughput tests, Ginkgo aims to quickly find the best combination of technical microbial compounds to produce a living biotherapeutic product (LBP). But even with an LBP, humans naturally produce by-products that attract insects.

Humans give off heat, carbon dioxide, and certain chemical elements and compounds called volatiles that quickly evaporate from the skin. If the compounds remained volatile, the repellant would only decrease the number of mosquitoes a person attracts rather than deter them entirely. However, if these volatile compounds can be identified, the project team could create a repellant with additional properties that prevent these compounds from evaporating in the first place.

A full stack partnership

In the first research phase of the project, Ginkgo plans to collaborate with leading mosquito researcher and neurogeneticist Matthew DeGennaro, Ph.D., of the Biomolecular Sciences Institute at the FIU. As an expert in molecular genetics and the mosquito odor attraction profile, DeGennaro can provide unique insights into the molecular connections required to keep mosquitos off over the long term.

Young caucasian man, bald, with clear glasses, wearing a dark blue suit and plaid shirt, looking at the camera

Matthew DeGenarro, Ph.D., of Florida International University, will provide key neurogenetic insights … [+] to the ReVector project.

Florida International University

Although popular products like DEET are considered effective, mosquito repellent technology hasn’t been updated in decades. “DEET has been the gold standard for repelling mosquitoes since the 1940s. Over the past 80 years [the science community] learned so much more about how mosquitoes find their hosts, ”DeGennaro said 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 use its extensive scientific knowledge of the skin microbiome to develop and characterize various strains of bacteria. To ensure the entire project runs smoothly from start to finish, the Latham BioPharm Group provides comprehensive program management, system integration support and expertise in regulatory strategies.

Project validation: testing, testing, 1,2, 3

The project is a four year effort divided into three key phases. First, the team will work to create and test as many potential repellants as possible. Ginkgo takes the repellants that show the most promising results and creates more microbial variations until they identify a few selected microbial strains with the most potent repellent properties.

In addition, some microbes, which may be less effective at repelling mosquitoes, are better able to mask volatiles. Understanding the various properties of the microbes is critical to developing an end product. Once this microbial cohort is identified, the team begins community modeling of the skin to ensure that the microbial strains can remain symbiotic on the skin for at least two weeks.

When the best microbes are identified and checked for safety, the human participants apply the repellent to their arms and place them in a container of mosquitos. When the mosquitoes are not attracted to human skin, the repellant does its job. While it sounds profoundly uncomfortable to the human participants, it’s also a simple, low-tech way to test the product in the field.

Looking beyond mosquitoes: a new approach to skin protection?

If the team can develop an appropriate repellant, 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, thereby enhancing our ability to ward off challenges such as mosquito-borne disease, has tremendous global health potential. Our research in collaboration with Azitra, FIU and LBG could have implications for the next generation of living medicine. ”

The protocols and lessons learned from this project could yield a genetic toolkit for harnessing the skin microbiome against other vector-borne diseases. While the COVID-19 pandemic is not a mosquito-borne disease, the importance of preventing pathogens between humans and animals is painfully clear. If successful, ReVector’s synthetic biology initiative could pave the way for other biotherapeutics.

For Zach Smith of Ginkgo, applications for microbiome technology aren’t necessarily limited to disease prevention. Smith is particularly interested in bio-engineered sunscreen. “We don’t know if it is possible, but if it is one [sun] A repellant that lasted a day would change me and my skin, ”says Smith.

The potential of using skin microbes against disease and damage is just being explored. Even if the project avoids setbacks, it will be years before this technology reaches the military. And it will likely take longer for civilians to benefit, if at all. The ReVector project also fails to reveal whether the end product could be available in developing countries where robust mosquito repellants are urgently needed.

But the partnership also shows how far synthetic biology has grown as an industry. This is not the field’s first partnership with DARPA. However, the broad coalition of biotech companies and experts is a promising indicator of the growth of the bioeconomy. While it’s too early to hang any hats, this new venture could mark a milestone in both synthetic biology and the long-standing battle against some of the world’s deadliest pathogens.

I’m the founder of SynBioBeta, and some of the companies I write about are sponsors of the SynBioBeta conference and weekly review, including Ginkgo Bioworks. I am also an operational partner at DCVC, an investor in Ginkgo Bioworks. Thanks to Vinit Parekh for additional research and reporting in this article.

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