DNA synthesis

Remember all those firsts for synthetic biology that we heard about coming from Craig Venter’s company, Synthetic Genomics in San Diego? The first genome of a whole organism transplanted. First genome synthesized. First synthetic life created.

A company was born to commercialize the technology from all that science, Codex DNA, which renamed itself Telesis Bio last year. Their product, called the BioXP, is a benchtop gene printer that uses enzymatic synthesis. Their competitive edge is the quality they offer—their genes have a higher accuracy rate. John Gill, Senior Director of Research and Innovation at Telesis Bio, joins us to talk about the company's vision and how they fit in what has become a dynamic marketplace for DNA.

Why does the improvement in quality mean so much in this field? How does this benchtop synthesizer differ from the other options in DNA and gene synthesis? And what applications can we look forward to as synthetic biology begins to change our world?

Has the pandemic unleashed the molecule of RNA to be the new future of drug development?

Tim Mercer is the Director of the BASE Lab at the University of Queensland which has recently become one of Australia’s leading national facilities for the manufacture and research of RNA technologies. Tim is the next guest in our series on enzymatic DNA synthesis which he says is "a quantum shift” in our ability to synthesize DNA.

Tim then goes on to explore the future of mRNA vaccines and other RNA therapeutics.

"There is a change in how the drugs are developed. It allows us to target diseases in ways that current drug development has been unable to address.”

For example, Tim discusses mRNA cancer vaccines and vaccines for rare diseases that are truly customized treatments.

"We can deliver a corrected version of a gene to the patient which is then expressed and translated in their cells and produces the corrected protein to clear the toxic metabolic products and essentially treat the disease. We're designing a particular drug to treat the disease."

If this isn’t trippy enough, we finish with a discussion of applications in synthetic biology. For Tim, it’s all the same thing whether it’s clinical applications or agriculture or industry.

“It’s all a spectrum,” he says.

The DNA synthesis space is seeing some real creativity and disruption this past year. One newcomer, in particular, is shaking things up.

Sylvain Gariel is the co-founder and chief operating officer of DNA Script, who has recently launched the world’s first benchtop enzymatic DNA synthesizer. In today's show, Sylvain, co-inventor of the new system, tells how he met his co-inventors at a French gas company and came to invent a whole new way of writing DNA.

“We spent a ton of time at the bench doing genetic engineering. And we started thinking, we are incredibly good at reading DNA, but we are still very inefficient at writing DNA. And the dream became very logical and very simple. What if you had a benchtop system that would be just like an Illumina MiSeq that would do all of that DNA work for you. That’s the dream, right?”

And that’s what they did. Voila! DNA Script's SYNTAX. It’s a remarkable story of scientists having a dream and executing on it to improve a technology that had been stagnant for years.

Today we get into the details. What is the bench top workflow, the turnaround time, the throughput? What are the hurdles for the market which has become used to ordering their oligos from providers the past twenty years? What is the company hearing from their customers a few months into the launch?

Join us as we dive deeper into this new technology for writing DNA.

“DNA is changing everything for the better,” says today’s guest, Emily Leproust, CEO of Twist Bioscience. Twist has emerged at the heart of what a New York Times Magazine write-up recently headlined The Gene Synthesis Revolution. 

For years, DNA synthesis plodded along as the straightforward “boring" industry underlying much more exciting work. It was the foundation of biotech and drug development and synthetic biology, yes, but what was there new to achieve with synthesizing plain old oligos?

Emily and her company have turned this paradigm upside down with a dynamic new model for what a DNA synthesis company might look like, being at the center of and affecting many new ventures and partnerships this past year. Early in 2022, they have announced a new method of DNA synthesis to enable better DNA storage—we dive into this early on in the program—and a new partnership with Pacific Biosciences. And late last year Twist spun out a drug development company based on their own research.

These are great times to be “Twisters!"

DNA is a multibillion-dollar industry in 2021 and satisfies many life science applications, including drugs, reagents, siRNA, PCR, diagnostics, synthetic biology, and many others. Enzymatic DNA synthesis, or EDS, is a new approach to manufacturing DNA that is much more efficient and user-friendly and could disrupt the current market.

Thomas Ybert is the CEO of DNA Script which is out with a new benchtop enzymatic DNA synthesizer called SYNTAX. He says in contrast to old chemical synthesizers, the new “DNA printer” takes virtually no expertise to run and will return much of the current business from service back to the old model where biologists make their own, having the power to “go from design to results in less than 24 hours.”

“[Biologists] are programming biological systems. DNA is the programming code. And you want this design-build-test cycle to go as fast as possible. It’s very clear that the next revolution will be from the life sciences. And we want to enable people to design-build-test super quickly.”

Investors appear happy with the company, just pouring in $165 million last month. The SYNTAX system is available now. With all that hassle of chemical synthesis cleared away by this new easy-to-use technology, will researchers and others return to making their own DNA?

In 2013 Twist Bioscience was a newcomer to a market that most of us thought was saturated, cornered, commoditized—that of synthetic DNA. But Emily Leproust and her co-founders saw something different. They saw "a big market with unhappy customers.” Today, with a radically disruptive technology, they are market dominant. Twist is a publicly traded company whose stock has doubled already once since they IPOd last year. Imagine, a DNA synthesis company going public! And then seeing their stock perform so well. This is tricky for the most hyped of tech or biotech startups.

And the demand for DNA is only going up, and dramatically up. When Twist signed a deal with Gingko Bioworks in 2017 for 1 billion bases, that single order was bigger than the entire market two years previous.

Today, for the first time the Twist CEO joins us on the program to talk about where her company came from (another planet?!) and about why there is such demand for DNA. What applications should we know most about? Is all this demand the result of hyped up investment, or are the products going to market?

“Synthetic biology is currently changing our lives and people don’t even realize it. People won’t say, 'oh that’s cool synthetic biology.' They won’t. They’ll just know they have a leather jacket. And there’s no cows harmed in the making of that leather jacket because that leather jacket was created from kampuchea and synthetic biology. And I think that’s the future of the impact of our industry.”

Guest:

Martin Trey, COO, Integrated DNA Technologies

Listen (4:32) The oligo factory

Listen (3:30) How have you stayed relevant in the age of sequencing?

Listen (3:39) A breakthrough in oligo length

Listen (7:18) A window on the industry

Listen (4:12) Thoughts on synbio

DNA. It’s at the core of biology and the life science industry. Integrated DNA Technologies, or IDT has been making DNA for the industry for twenty five years.

Mendelspod has been working for some time now to persuade someone from IDT to come on the program and tell us about their history--how they began, why they're in Coralville, Iowa, and what important trends they're observing.

Beginning a new series entitled Beyond the Oligo, we’re joined by IDT’s Chief Operating Officer, Trey Martin, for a wide ranging discussion about the company beginnings and their unique perspective on a rapidly changing industry.

Further episodes of this series will feature some of IDT's customers-from clinical genomics to synthetic biology-who are using DNA to pioneer dramatic new advances in human health and the way we are moving forward as a species.

Podcast brought to you by: Chempetitive Group - "We love science. We love marketing. We love the idea of combining the two to make great things happen for your marketing communications."

Podcast brought to you by: Chempetitive Group - Who for more than a decade has helped science-based companies build and execute innovative marketing campaigns. "We love science. We love marketing. We love the idea of combining the two to make great things happen for your marketing communications."

Guest:

Kevin Munnelly, CEO, Gen9 Bio and contact Info

Chapters: (Advance the marker)

0:39 A disruptive change to synthetic biology

6:56 Why hasn't gene synthesis progressed along with sequencing?

10:14 Looking at the market: applications for synthetic biology

15:29 Educating the market the biggest challenge

19:01 PR efforts going into biosecurity

25:07 Personal path to Gen9

As part of our series on synthetic biology, we talk with Kevin Munnelly, CEO of Gen9, a new gene synthesis company founded by George Church of Harvard, Joseph Jacobson of MIT, and Drew Endy of Stanford. According to Munnelly, Gen9 is not just another gene synthesis company, but one which will dramatically disrupt the space. The theory is that just as the declining cost of sequencing has enabled new applications for genomics, so too will a drastically reduced price for synthetic genes. Kevin believes we are just at the beginning of a synthetic biology revolution and it's new technology such as his that will enable it. What are these new applications and why hasn't gene synthesis kept pace with sequencing we ask Kevin in today's show.