DNA Script Develops World’s First Enzymatic DNA Printer
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The octopus is a solitary creature that doesn’t find dating to be all that. When it comes time to mate, the male sends the female a sperm pouch from afar, sometimes with a severed arm attached. And they said romance was dead. In addition to being intelligent enough to avoid child support and alimony, the octopus is capable of changing its own genetic makeup to adapt to its environment. Scientists are studying this trait in hopes to mimic this feat for therapeutic applications. The act of taking something remarkable from nature and “productizing” it is referred to as biomimicry.
In a previous article, we looked at 8 Biomimicry Examples Taken From Actual Startups looking to mimic sharks, beetles, spiders, bamboo, and even glow worms. Why reinvent the wheel when evolution already invested centuries of time sorting it out? That’s the thought process behind the work being done by a French startup called DNA Script which has decided that the traditional DNA synthesis technology being used today that was invented in the 80s needs a refresh.
Illumina (ILMN) has enjoyed a great deal of success because they sell machines used to read DNA. It’s a process called “next generation sequencing,” and it’s what made the entire field of synthetic biology possible. Once we can read DNA, we can then start to understand it. When we understand DNA, we can start to edit it. That’s why all these gene-editing companies are cropping up. Once we’ve edited a piece of DNA, we may then want to produce strands of DNA on demand. We refer to the process of creating DNA as “DNA synthesis.”
All DNA synthesis involves making short fragments of DNA called oligonucleotides (oligos), and then using enzymes to sew them together. Companies like Twist Bioscience have built an entire business around producing synthetic DNA on demand. Traditionally, the process of synthesizing DNA involved the use of chemicals. DNA Script’s technology uses biomimicry to allow researchers to perform DNA printing in their very own labs.
DNA Script and the DNA Printer
We first came across French startup DNA Script a few years back when we wrote about 9 DNA Data Storage Companies to Watch. Since then, they’ve taken in some major funding rounds having raised just over $112 million to date from big-name investors like Danaher Life Sciences (DHR), Agilent Technologies (A), Merck (MRK), and Illumina Ventures. To better understand what the company does, we turned to a talk given by co-founder Thomas Ybert in 2017 which introduces the technology as a form of biomimicry.
Update 01/12/2022: DNA Script has raised $35 million in extended Series C funding that brings the round total to $200 million to help promote the launch of its new systems. This brings the company’s total funding to $479.8 million to date.
The talk starts out with some more interesting examples of biomimicry – a train design inspired by the Kingfisher bird, an adhesive based on the gecko skin, and a vaccine that mimics the tardigrade. The takeaway here is that natural evolution provides many solutions to complex problems, one of those being DNA synthesis. DNA Script wants to upend DNA synthesis by switching from chemicals to enzymes.
We’ve recently written about how proteins are some of the most amazing molecular machines known to man. One class of proteins are enzymes, molecules that act as catalysts for chemical reactions. One type of enzyme is a DNA polymerase which is best explained by News Medical as follows:
The DNA polymerases are enzymes that create DNA molecules by assembling nucleotides, the building blocks of DNA. These enzymes are essential to DNA replication and usually work in pairs to create two identical DNA strands from one original DNA molecule. During this process, DNA polymerase “reads” the existing DNA strands to create two new strands that match the existing ones.Credit: News Medical
Since DNA polymerases are nature’s way of copying DNA, they’re probably pretty good at it. DNA Script’s approach is to engineer these enzymes to naturally perform DNA synthesis that’s faster, cheaper, and more environmentally friendly than existing methods of writing DNA. Their finished product is a benchtop DNA printer powered by their enzymatic technology which “delivers a faster and environmentally-friendly alternative to outsourced, chemical-based DNA synthesis.”
Many big pharma R&D departments will feel a whole lot better being able to print DNA themselves without having to involve a third-party vendor such as Twist Biosciences. However, DNA Script isn’t the only startup dabbling in enzymatic DNA synthesis or desktop DNA synthesis machines.
A whole new generation of companies are working on using enzymes to improve DNA synthesis. One of these is startup Molecular Assemblies which is working on “an enzymatic, platform-independent synthesis technology that produces long, high-quality, sequence-specific DNA reliably and affordably.” They’re also backed by Agilent, and they recently got into bed with a publicly traded protein engineering company we wrote about just days ago. Another startup working with the University of Berkeley on DNA synthesis using the enzyme approach is Ansa Biotechnologies.
When it comes to printing DNA, one competitor in this space is Evonetix, a U.K. startup that’s developed a unique silicon chip that allows large-scale DNA synthesis to occur in parallel. Their desktop DNA writer will be a ‘plug and play’ instrument that’s easy to use.
Evonetix describes their technology as “a process that identifies and removes errors, enabling accuracy, scale and speed that is several orders of magnitude better than conventional approaches.” The startup closed their largest funding round to date – a $30 million Series B – this past March bringing their total disclosed funding to $44 million to date.
With all the progress being made with DNA synthesis, we’re a long way from being able to stitch together an entire genome. A complete DNA strand is estimated to be about two yards long and contains about as much information as can be found in the below stack of phone books.
The longer the strand of DNA you’re trying to produce, the more likelihood there will be errors. Both accuracy and speed are paramount. Startups like Ribbon Biolabs are using enzymatic synthesis technology to manufacture large lengths up to 10K base pairs in just hours. Using the enzymes found in nature, genome-scale synthesis may soon become a reality.
Lastly, it’s worth mentioning a pioneer in the DNA printing space – Synthetic Genomics – which markets their DNA printer under a subsidiary called Codex DNA. The BioXp 3200 system is “the world’s first and only fully automated gene synthesis platform for personalized medicine and distributed vaccine manufacturing.” Founded by Dan Gibson — the creator of the industry-standard Gibson Assembly methodology – Codex DNA requires their clients to order sequence-specific DNA cartridges which can take 3 to 5 days to arrive. It’s hard to see why you would want to purchase the equipment if it takes the same amount of time for someone else to do the work.
The speed at which technology develops will increase as we accumulate more data than ever before and feed it to machine learning algorithms that help us solve problems quicker. The enzymatic DNA printer developed by DNA Script is the first of its kind and has attracted interest from large corporations that want to keep tabs on how this develops. Changing the business model from an outsourced service to a closed-loop hardware platform is something Twist Bioscience is sure to be keeping close tabs on.
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