Writing business

Can a desktop DNA printer prevent the next pandemic?

The Boston Consulting Group predicts that the size of the global bioeconomy will be $30 trillion by the end of the decade. A key driver of its rapid growth has been reducing the cost and turnaround time of DNA sequencing. Reading DNA allowed us to decipher the human genome and paved the way for personalized medicine. It enabled the design of the COVID-19 vaccine in record time and helped us track the emergence of new variants. And now we’re seeing another groundbreaking innovation in biology – the ability to write DNA on demand.

Everything the bioeconomy relies on uses DNA, which encodes the genes for enzymes, proteins and living organisms used in biotechnology. These four letters – A, C, T and G – are the source code for every project, whether it’s biofuels, vaccines and therapeutics, or animal-free meat. Without DNA, there is no biotechnology. But the way the business model currently works is that you have to order DNA sequences from third-party companies like Twist Biosciences, IDT
, Eurofins GenomicsWhere GenScript. The larger the size of the DNA fragment, the longer it takes to synthesize it. So by the time it gets to the researcher, it can take anywhere from a few days to several weeks.

Telesis Organic (NASDAQ
:DNAY) is changing that. They want to bring the ability to write DNA to every lab with their desktop automated gene synthesis platform, Digital-to-biological converter™ (DBC
). Formerly known as Codex DNA, the company was founded in 2011 by a team of synthetic biology innovators. Company CEO Todd Nelson knows a thing or two about making DNA. Born in Park City, Utah, a former ski pro started out in investment banking on Wall Street, but then gave up the dashing race and moved to San Diego, California. He first got into the DNA business as a board member of a Seattle company called Blue Heron Biotechnologies. Blue Heron was the first company to offer commercially available synthetic genes around 2005-2006, creating a model for DNA synthesis companies that exist today.

The other members of the Telesis Bio executive suite have no less impressive resumes. The team of technology innovators is led by renowned genetic jockey Dan Gibson, CTO. Dan took his break working for Craig Venter who first sequenced the human genome in 2001. The gold standard method for assembling long pieces of DNA from many shorter pieces is named after him – the Gibson Assembly ®. Dan, along with Craig Venter and John Gill, was the co-inventor of the BioXp™ system – Telesis Bio’s flagship offering – which is an end-to-end turnkey solution for generating synthetic DNA and mRNA .

The BioXp™ 3200 has become the first fully automated platform capable of assembling DNA fragments of several thousand bases virtually overnight, allowing any laboratory to become its own gene supplier. But Telesis Bio didn’t stop there: they tweaked the instrument to expand its capabilities to make mRNAs, clone longer fragments, and perform other synthetic biology tasks entirely hands-on. free. Their new instrument, BioXp™ 9600, has been dubbed an “automated synthetic biology workstation” and is poised to expand beyond just DNA assembly and cloning capabilities. With it, scientists will have the ability to synthesize their own DNA right on the desktop without the need to order custom reagents.

A better way to make DNA

Typically, DNA synthesis begins by taking four bottles of chemicals, each corresponding to one of the letters of the genetic code, and bringing them together in a chemical reaction. This time-consuming process was first developed in the 1980s and involves the use of toxic chemicals. One of the things Telesis Bio is doing is replacing chemical synthesis with faster, more benign enzymatic chemistry. They have developed a new DNA synthesis chemistry known as SOLA (short oligonucleotide ligation assembly), which will be integrated into the BioXP™ 9600 system in 2023.

Enzymatic DNA synthesis is not a new idea: other companies, such as Molecular assemblies, DNA script, Evonetix, Touch Light Geneticsand ANSA, also settle in this space. But what sets Telesis Bio apart is that they have integrated this technology into a scalable desktop solution. Their BioXp™ 9600 system, already available to pharmaceutical and biotech customers, will enable companies to become self-sufficient in DNA synthesis and significantly reduce project timelines.

“A desktop DNA printer will allow you to create any gene, anytime and anywhere, so you can be your own DNA source and collaborate globally,” envisions the CEO. The first SOLA kits will be for making CRISPR guide RNAs (gRNAs) and will allow scientists to go from digital gRNA designs to holding a tube of these reagents in their hands the same day.

Vaccines that can be printed almost instantly

The global gene synthesis market is currently valued at $1.8 billion and is expected to grow at a compound annual growth rate of 17.5%. The applications of this technology span various areas of discovery: from vaccines to precision immunotherapy for cancer and therapeutic antibodies to modified meat substitutes and sustainable cellular agriculture products. For all of these applications, but especially vaccines and therapeutics, speed is key, which is why having a desktop DNA printer can be a game-changer.

“Imagine a global network of these desktop printers that could prevent the emergence of the next pandemic by printing fast mRNA vaccines. The technology to enable this isn’t too far off,” Todd thinks.

The company has already partnered with Pfizer
to allow them early access to SOLA technology for uses such as the development of mRNA vaccine candidates for emerging pathogens. Telesis Bio bets on installing this machine on the desk of every laboratory in the world to accelerate the development and deployment of new drugs.

Fighting diseases with gene and cell therapies

Another area where rapid DNA synthesis technology can have a big impact is in gene and cell therapies, such as T-cell receptor (TCR)-based cancer therapy. This approach uses genetically modified immune cells to attack solid tumors. The modified TCRs target the tumor by recognizing specific markers that make cancer cells different from healthy cells. With the BioXP™ instrument, you can build these TCRs overnight. The faster you get to cancer, the better your chances of survival.

DNA printing could also open up the possibility of treating inherited diseases with gene therapy using CRISPR gene-editing technology. CRISPR is already being used to edit the genomes of microbes to produce everything from drugs to materials to chemicals. There are also over 100 CRISPR gene-editing drug trials underway right now. What is required for any gene editing experiment are guide RNAs that help distinguish the gene being edited. The DBC instrument coupled with SOLA kits would enable gRNA synthesis at the push of a button, which could dramatically accelerate progress in these areas.

Being able to store all the data in the world in a test tube – and more

The storage of DNA data is another promising application area for the technology that Telesis Bio is developing. Instead of using zeros and ones as input, DNA data storage uses the four letters of the genetic code to store information. The DNA code has 64 times the information density and is extremely chemically stable, so every bit of data we have in the world today could be encoded in DNA, synthesized, and stored in a tube. test. Some companies are already going from digital to DNA: data storage giant Seagate Technology recently partnered with a starter catalog to do just that. Twist Bioscience, which runs a central DNA production service, has partnered with Microsoft
and the University of Washington to work on DNA storage research.

And that’s just the beginning. All other applications of the bioeconomy – from biofuels to cellular agriculture – require writing DNA. There is unlimited potential for companies like Telesis Bio when it comes to driving innovation: “The BioXP™ is like an iPhone: we’ve built an incredible platform and now it’s all about the apps you run on it”, Todd predicted.

There are other DNA synthesizers, each offering their own version of the technology. A company called kilobase released a desktop DNA and RNA synthesizer, which uses traditional chemical synthesis to print short pieces of DNA (called oligos), one at a time. DNA Script is out a multiplex DNA synthesizer which can print oligos up to 45 bases and Evonetix comes out with a desktop computer which allows an even longer oligo synthesis. Telesis Bio seeks to extend current technological capabilities to provide researchers with rapid, accurate and multiplexed on-demand long fragment DNA synthesis coupled with other synthetic biology workflows.

“Telesis Bio is much more than a DNA synthesis company. We want to enable researchers to become their own service provider with the highest quality, tailored DNA, RNA and potentially proteins,” Todd said. The recent name change from Codex DNA to Telesis Bio reflects the company’s major plans to break out of the existing paradigm of centralized synthesis centers to enable researchers from anywhere to manufacture their own DNA and RNA products. .

Thanks for Katia Tarasava for additional research and reporting on this article. I’m the founder of SynBioBeta, and some of the companies I write about, including Telesis Bio, Twist Bioscience, Molecular Assemblies, and DNA Script, are sponsors of the SynBioBeta Conference and weekly summary.