DNA synthesis is one of the pillars of Covid-19 research that has suffered supply disruptions during lockdowns. Thomas Ybert, CEO of DNA Script, discusses the French company’s plans to protect research from future disruptions by giving every lab the ability to synthesize its own DNA molecules.
The Covid-19 pandemic has highlighted more than ever the importance of medical research. However, the lockdown has affected vital parts of the research and development process to create new treatments and diagnostics. One of them is the synthesis of DNA, which is still mostly outsourced to third parties and requires on-demand delivery.
Thomas Ybert co-founded the Paris-based DNA Script in 2014 to develop equipment that allows labs to synthesize their own DNA molecules within hours. This could be convenient for the average researcher, who normally needs to wait up to several days for the arrival of molecules from centralized suppliers. To Ybert, DNA Script’s mission has never been more relevant than during the Covid-19 pandemic.
“From the very first day Covid-19 hit different Western countries, we were contacted by some groups in the US and Europe, in order for those groups to get really quick access to DNA. All of those teams shared their stress,” Ybert reflected.
DNA molecules are needed for Covid-19 tests, particularly those that detect viral genetic material via a technique called PCR. With widespread testing, it’s possible to isolate infected people and slow the spread of the virus.
“All PCR tests involve synthetic DNA. You need a DNA primer in order to detect the genomic DNA that is potentially present in the sample,” Ybert said.
Having easy access to synthetic DNA is also crucial for speeding up the development of better PCR tests for Covid-19.
“You need to iterate a lot on designing these tests to find the perfect set of primers that will have the sensitivity necessary to detect the virus,” Ybert said. “If you take three weeks to develop such a test, that’s three weeks you’re lagging behind the viral infection.”
Additionally, synthetic DNA is used to carry out genomic studies of the virus responsible for Covid-19, which help to track the virus’s spread and evolution.
“Those are very critical activities,” remarked Ybert. “If you’re able to detect the virus way ahead in the environment before it’s infecting the first human, or when it’s infecting the first human, you can quickly identify what the cause is. You’re just winning a lot of time in the process.”
Centralized DNA synthesis is inadequate against pandemics
The outsourcing of DNA synthesis has served the needs of many researchers for a long time, but is also vulnerable to the disruptions caused by a pandemic.
One major weakness of the centralized system is that delivery companies such as FedEx and UPS can experience delays, slowing the arrival of DNA to where it’s needed. Additionally, nationwide lockdowns can all but paralyze some DNA production centers.
“There are very few centers of production in the world, so if they go into lockdown, then you’re screwed; you cannot get access to DNA anymore,” Ybert explained.
According to Ybert, there have also been cases where DNA products from suppliers were contaminated with DNA of the coronavirus that causes Covid-19. This contamination may come from positive control samples that are manufactured at the same location for Covid-19 diagnostics kits. Or worse, it could even come from employees that are infected with the virus.
“You’re asking them to give you a primer to develop your [Covid-19] test, but this primer is contaminated,” Ybert said. “Now, when you’re developing your test, every iteration is giving you a positive reading. That’s super bad.”
DNA synthesis in your own lab
DNA Script develops equipment that lets labs produce the DNA molecules they need onsite. The machine uses engineered enzymes to make the DNA molecules within a day. Since the kits needed to make the DNA can be stored for months, the lab could be self-sufficient to synthesize DNA during a crisis situation.
Not only could the gear help labs to withstand a pandemic situation, but it could be a game-changer for labs that are near to new outbreaks. Currently, the wait for DNA molecules means these labs need time to develop tests for new pathogens.
“If you are a hospital, or the CDC, or a lab in China close to those markets where people are in close contact with animals — as the hypothesis for the emergence of Covid-19 suggests — you cannot throw the perfect DNA primer to detect Covid-19 because you don’t know about the existence of Covid-19 at that time, or let’s call it Covid-25 in five years from now,” explained Ybert.
With DNA Script’s machine and kits, these peripheral centers could develop DNA primers within hours and start testing. Quickly identifying the first cases could stop localized outbreaks from becoming full-blown pandemics, and therefore avoid the enormous economic and human costs of bringing the situation under control.
“There are billions of lives and trillions of dollars that separate these two scenarios, which I think is really, really important,” Ybert told me. “It’s true for viruses and Covid-19, but it’s also true for any infectious disease.”
One potential drawback of DNA Script’s decentralized approach is that the quality of DNA primers may vary across different locations. This in turn could slow down research because scientific experiments can’t be easily reproduced. DNA Script is assessing this variability in an ongoing evaluation program.
Now that the technology is under evaluation, Ybert hopes to see it field-tested with partner organizations later this summer, though the exact dates will depend on how the Covid-19 situation progresses.
Progress in the face of Covid-19
There could be a bright future for the field of DNA synthesis in spite of the pandemic disruption. According to Ybert, the field’s trajectory may end up a strong parallel to the emergence of next-generation sequencing, which revolutionized the life sciences.
“Next-generation sequencing just enables so many different things. We are still discovering applications of next-generation sequencing,” he noted. “Secondly, the market expanded like crazy. I see exactly the same in the DNA synthesis path with the introduction of new technology.”
Ybert believes that, with the democratized DNA synthesis that DNA Script aims to foster, the field could also see a veritable explosion in the applications of the technology.
“To me, people with such a tool are going to synthesize DNA like crazy and then, the result of that will be a formidable extension of the DNA market,” he concluded.
Cover picture provided by DNAScript and edited by Elena Resko. This interview was originally published in June 2020.