DNA Script has raised $38.5 million in new financing to commercialize a process that it claims is the first big leap forward in manufacturing genetic material.
The revolution in synthetic biology that’s reshaping industries from medicine to agriculture rests on three, equally important pillars.
They include: analytics — the ability to map the genome and understand the function of different genes; synthesis — the ability to manufacture DNA to achieve certain functions; and gene editing — the CRISPR-based technologies that allow for the addition or subtraction of genetic code.
New technologies have already been introduced to transform the analytics and editing of genomes, but little progress has been made over the past 50 years in the ways in which genetic material is manufactured. That’s exactly the problem that DNA Script is trying to solve.
Traditionally, making DNA involved the use of chemical compounds to synthesize (or write) DNA in chains that were limited to around 200 nucleotide bases. Those synthetic pieces of genetic code are then assembled together to make a gene.
DNA Script’s technology holds the promise of making longer chains of nucleotides by mirroring the enzymatic process through which DNA is assembled within cells — with fewer errors and no chemical waste material. The enzymatic process can accelerate commercial applications in healthcare, chemical manufacturing, and agriculture.
“Any technology that can make that faster is going to be very valuable,” says Christopher Voigt, a synthetic biologist at the Massachusetts Institute of Technology in Cambridge, told the journal Nature. “There is no Nobel prize that needs to happen,” Leproust says. “It’s just hard engineering.”
DNA Script isn’t the only company in the market that’s looking to make the leap forward in enzymatic DNA production. Nucleara, startup working with Harvard University’s famed geneticist, George Church, and Ansa Bio, a startup affiliated with Jay Keasling’s Berkeley lab at the University of California are also moving forward with the technology.
But the Paris-based company has achieved some milestones that would make its technology potentially the first to come to market with a commercially viable approach.
At least, that’s what investors new investors LSP and Bpifrance, through its Large Venture fund, are hoping. They’re joined by previous investors Illumina Ventures, M. Ventures, Sofinnova Partners, Kurma Partners and Idinvest Partners, in backing the company’s latest funding.
The company said the money would be used to accelerate the development of its first products and establish a presence in the United States.
“As we announced earlier this year at the AGBT General Meeting, DNA Script was the first company to enzymatically synthesize a 200mer oligo de novo with an average coupling efficiency that rivals the best organic chemical processes in use today,” said Thomas Ybert, chief executive and cofounder of DNA Script. “Our technology is now reliable enough for its first commercial applications, which we believe will deliver the promise of same-day results to researchers everywhere, with DNA synthesis that can be completed in just a few hours.”
Prominent genetic “biohacker” Josiah Zayner is under investigation by California state officials for practicing medicine without a license.
Zayner has a background in biophysics and runs a company called The Odin, which sells do-it-yourself genetic engineering kits and other lab equipment intended for use outside of scientific laboratories. The kits and tools are intended to allow lay users to genetically modify bacteria, yeast, animals, and even humans.
Solugen, a startup that has set itself up with no less lofty a goal than the decarbonization of a massive chunk of the petrochemical industry, may be the first legitimate multi-million dollar company to start out in a meth lab.
When company co-founders Gaurab Chakrabarti and Sean Hunt began hunting for a lab to test their process for enzymatically manufacturing hydrogen peroxide they only had a small $10,000 grant from MIT — which was supposed to pay their salaries and cover rent and lab equipment.
Chakrabarti, who now jokingly calls himself “the Heisenberg of hydrogen peroxide” says that the lab spaces they looked at initially were all too pricey, so through a friend of a friend of a friend, he and Hunt wound up leasing lab space in a facility by the Houston airport for $150 per month.
It was there among the burners and round-bottomed flasks that Hunt and Chakrabarti refined their manufacturing process — using fermentation based on Solugen’s proprietary enzyme made from genetically modified yeast cells to produce hydrogen peroxide.
“In 2016 I went to visit Solugen’s headquarters in Houston, They were subleasing a small part of a bigger lab and it was one of the sketchiest labs I’d seen, but the Solugen founders liked it because the rent was low” recalls Solugen seed investor, Seth Bannon, a founding partner with the investment firm Fifty Years. “Sean and Gaurab were incredibly impressive. They had their prototype reactor up and running and were already selling 100% of its capacity, so we invested.”
Creating a process that can make thousands of tons of chemicals — without relying on petroleum — would be a hugely important step in the fight against global climate change. And Solugen says it has done exactly that — while getting the chemical industry to subsidize its development.
The chemicals industry is responsible for 10% of global energy consumption and 30% of industrial energy demand, while also contributing 20% of all industrial greenhouse gas emissions, according to the website Global Efficiency Intelligence.
As the world begins to confront the effects of global climate change, curbing emissions from industry will be critically important to ensuring that the world is not irrevocably and catastrophically changed by human activity.
Greenhouse gas emissions are only one of the dangers associated with the petrochemical industry’s approach to production. The processes by which chemicals are made are also incredibly volatile, and the work is dangerous for both employees and the communities in which these plants operate.
Last week, a chemical plant explosion has led to one of the worst fires in the city’s history. Firefighters in the city spent six days trying to contain a chemical fire that has burned 11 storage tanks managed by Intercontinental Terminals Company.
“They’re moving chemicals exposed to the environment, and those chemicals are not designed to be transported in that way,” Francisco Sanchez, the county’s deputy emergency emergency management coordinator told The Houston Chronicle.
Man in protective workwear with Caution cordon tape (Courtesy Getty Images)
By contrast, Solugen’s process is only a little more dangerous than brewing beer.
In the years since Bannon came to visit the company in its first lab, Solugen has built a working production plant capable of making enough hydrogen peroxide to bring in tens of millions of dollars in revenue for the company.
In addition to its current mobile manufacturing facility, a skid mounted 1,000 square foot mini plant, Solugen is using $13.5 million in new financing from investors to build a new, 2,500 modular facility which will produce 5,000 tons of hydrogen peroxide per year.
That new money came from the investment fund Founders Fund (co-founded by the controversial libertarian investor, Peter Thiel), Fifty Years, and Y Combinator.
Solugen’s secret sauce is its ability to create oxidase enzymes cheaply that can be combined with simple sugars to make oxidation chemicals — which account for roughly half of the $4.3 trillion dollar global chemical industry.
The companies bioreactors have been specifically designed fir the chemicals it makes, but the real innovation is looking at enzymes as a tool for oxidation chemistries.
Companies are now able to engineer these enzymes thanks to advances on computational biology and the newfound ability of biochemists to engineer DNA, Chakrabarti says.
Solugen uses CRISPR gene editing technologies to modify yeast cells. It has identified a certain transcription factor which acts like an accelerant to producing the enzyme that Solugen’s process requires. Messenger ribonucleic acid overwhelms most of the typical processes if a celll to force the cell to dedicate most of its function toward enzyme production. The company then uses a contract research organization to cheaply make the enzyme at scale.
Companies also have driven down the cost of manufacturing these specialty enzymes. “The revolution is the commoditization of biomanufacturing specifically enzyme production,” he says. “Instead of our enzymes costing $1,000 per kg… It’s $1 to $10 per kg.”
Once Solugen proves that the new facility can work, the only issue is scaling, according to Chakrabarti. “We use enzyme technologies to create chemical mini-mills [and] each mini-mill can do 5,000 tons of products,” says Chakrabarti.
A typical chemical [lant has a production capacity of 50,000 tons, but the Solugen process is orders of magnitude more inexpensive, says Chakrabarti. That allows the company to build out a network of smaller plants profitably. “These are huge industries where we can make cheaper products,”he says.
And for every ton of product that Solugen makes and sells, it’s the equivalent of removing six tons of carbon from the atmosphere, Chakrabarti says.
Oil and gas companies have already signed contracts and are ordering the company’s products to the tune of several million in sales.
“It’s a nice way of funding us and funding the oil and gas industry’s demise,” says Chakrabarti of the company’s sales to its initial customers, “They give us money and allow us to go after other chemistries that would have been petroleum based… Our ultimate goal is to wipe them out.”
Now the World Health Organization is taking its first steps to regulate the use of the technology.
“Gene editing holds incredible promise for health, but it also poses some risks, both ethically and medically,” said says Dr Tedros Adhanom Ghebreyesus, WHO Director-General. in a statement.
For the past two days the WHO’s committee of experts hashed out a few first steps for governing research around human gene editing, including a baseline agreement that working on any cliniaxal applications would be irresponsible.
The committee also called on WHO to create a central registry for all of the research being conducted on editing the human genome, to create a database of all ongoing work.
“The committee will develop essential tools and guidance for all those working on this new technology to ensure maximum benefit and minimal risk to human health,” said Dr Soumya Swamanathan, WHO Chief Scientist, in a statement.
Gene drive is both a promising and disturbing technology. It allows us to engineer a stretch of DNA that, once inserted in a specific location in an organism’s genome, will convert other versions of the gene so that they also carry the insert. Once started in a population, gene drive will convert the entire population within a relatively short number of generations.
That’s promising, in that it opens the door to editing mosquitos to cause sterility to spread through a population, eliminating the spread of diseases and a fair bit of itching. But it’s also a genie that, once out of the bottle, appears to be impossible to put back—and hence is disturbing. But so far, there has been a small consolation: it has only been shown to work in insects.
Now, a large research team at the University of California, San Diego, has managed to get it working in mice. Sort of. It turns out that the efficiency is much lower. While the gene drive DNA is inherited at rates well above normal Mendel-style inheritance, it’s nowhere near as effective as in insects, and it’s not clear we know how to fix it.
Chinese authorities have declared the work of He Jiankui, who shocked the scientific community by claiming he successfully created the world’s first gene-edited babies, an illegal decision in pursuit of “personal fame and gain.” Investigators have completed preliminary steps in a probe that began in November following He’s claims and say they will “seriously” punish the researcher for violations of the law, China’s official news agency Xinhua reported on Monday.
He, who taught at Shenzhen’s Southern University of Science and Technology, had led a team to research the gene-editing technique CRISPR since mid-2016 in attempts to treat cancers and other diseases. The incident drew significant attention to the professor’s own biotech startups that are backed by local and overseas investors.
The official probe shows that He fabricated ethics approvals which he used to recruit eight couples to participate in clinical procedures between March 2017 and November 2018. The attempt led to two pregnancies, including one that resulted in the birth of twins and the other embryo yet to be born. Five couples failed to achieve fertilization and one pair dropped out of the experiment.
He’s project has sparked a wave of criticism among scientists across the world. CRISPR is still dangerously unethical at this point for it may cause serious genetic damage. Some researchers have proposed a moratorium on CRISPR until more guidelines become clear while others call for developing safer and more ethical methods to propel the technology forward. Many countries, including the United States and China, prohibit gene-editing of human embryos for reproductive purposes.
The up to $818 million deal between Locus Biosciences and Janssen Pharmaceuticals (a division of Johnson & Johnson) that was announced yesterday points toward a new path for CRISPR gene editing technologies and (potentially) the whole field of microbiome-targeted therapies.
Based in Research Triangle Park, N.C., Locus is commercializing research initially developed by scientists at North Carolina State University that focused on Cas3 proteins, which devour DNA Pac-Man-style, rather than edit it like the more well-known Cas9-based CRISPR technologies being used by companies like Caribou Biosciences, Editas Medicine, Synthego, Intellia Therapeutics, CRISPR Therapeutics and Beam Therapeutics.
While the Cas9 CRISPR technologies can edit targeted DNA — either deleting specific genetic material or replacing it with different genetic code — Cas3 simply removes DNA strains. “Its purpose is the destruction of invading DNA,” says Locus chief executive, Paul Garofolo.
The exclusive deal between Janssen Pharmaceuticals and Locus gives Janssen the exclusive license to develop, manufacture and commercialize CRISPR-Cas3-enhanced products targeting bacterial pathogens for the potential treatment of respiratory and other organ infections.
Under the terms of the deal, Locus is getting $20 million in upfront payments and could receive up to $798 million in potential future development and commercial milestone payments and any royalties on potential product sales.
A former executive at Valiant Pharmaceuticals and Paytheon, Garofolo was first introduced to the technology that would form the core of Locus as an executive in residence at North Carolina State University. It was there that he met Dr. Chase Beisel and Rodolphe Barrangou, whose research into Cas3 proteins would eventually be productized by Locus.
The company spun out of NC State in 2015 and raised its first cash from the North Carolina Biotech Center a year later.
Locus is already commercializing a version of its technology with bacteriophages designed to target e coli bacteria to treat urinary tract infections. The company is on target to begin its first clinical trials in the third quarter of the year.
The focus on bacterial infection and removing harmful bacteria while ensuring that the rest of a patient’s microbiome is intact is a huge step forward for treating diseases that scientists believe could be linked to bacterial health in a body, according to Garofolo.
“Most microbiome companies are about adding probiotics to your body,” says Garofolo, representing a thesis that introducing “good” bacteria to the body can offset any harmful pathogens that have infected it.
“Things you’re exposed to are creating the groundwork for an infection or disease, or exacerbating an existing disease,” says Garofolo. And while he believes that the microbiome is the next big field for scientific discovery, the approach of adding probiotics to a system seems less targeted and effective to him.
Already, Garofolo has managed to convince investors of his approach. In addition to the initial outside investment from the North Carolina Biotech Center, Locus has attracted $25 million in financing from investors, including Artis Ventures and the venture capital arm of the Chinese internet giant, Tencent.
Meanwhile, investors have spent millions backing alternative approaches to improving human health through the manipulation of the microbiome.
Companies like Second Genome, Viome and Ubiome are all using approaches that identify bacteria in the human body and try to regulate the production of that bacteria through diet and probiotic pills. It’s an approach that allows these companies to skirt the more stringent requirements the Food and Drug Administration has put in place for drugs.
That doesn’t mean that extensive amounts of research haven’t gone into the development of these probiotics. Seed, a Los Angeles-based startup that launched last year, has recruited as its chief scientist George Reid, the leading scientist on microbial health and the microbiome.
Founded by Raja Dhir, a graduate from the University of Southern California and a leading researcher on microbiotics in his own right, and Ara Katz, the former chief marketing officer of BeachMint and an MIT Media Lab fellow, Seed focuses on developing probiotic treatments using well-established research.
“Foundational to our approach is that it’s not which microbes are present in your gut… It’s based on looking at what specific microbes can do to a healthy individual to improve that status of health independent of what is already present,” Dhir said in an interview around the company’s launch last June. “It’s a little bit less exciting from a tech perspective, but it’s hardcore grounded in basic science… The question is, does this have changes and effects in validated bio-makers in a controlled and placebo setting?”
Dhir said that a basic understanding of how different bacteria can influence health is necessary before getting into the benefits of personalization.
“These things can dance between drugs and nutrition,” Dhir said. “Probacteria are an additional lever that people should pull… like diet and exercise and cessation of smoking… In every correspondence we always have been and need to be clear that this should never be seen as a replacement of therapies.”
By contrast, the tools that Locus is developing are very much therapies with potentially far-reaching implications for illnesses, from irritable bowel syndrome to gastrointestinal cancers and even neurological disorders.
“The science [around the microbiome] is early, but it is very well-known that a potentially deadly pathogen should be removed from your body,” Garofolo said.
As more details regarding the first gene-edited humans are released, things continue to look worse. The researcher who claimed the advance, He Jiankui, has now given a public talk that includes many details on the changes made at the DNA level. The details make a couple of things clear: we don’t know whether the editing will protect the two children from HIV infections, and we can’t tell whether any areas of the genome have been damaged by the procedure.
All of that raises even further questions as to whether He followed ethical guidelines when performing the work and getting consent from the parents. And, more generally, nobody is sure why He chose to ignore a strong consensus that the procedure wasn’t yet ready for use in humans. In response to the outcry, the Chinese government has shut down all further research by He, even as it was revealed that a third gene-edited baby may be on the way.
While the US already has rules in place that are intended to keep research like He’s from happening, a legal scholar Ars spoke with suggested there may be a loophole that could allow something similar here. In light of that, it’s important to understand the big picture He has potentially altered. What exactly happened in China and why does it concern so many in the scientific community?