Boston Consulting Group predicts that the size of the global bioeconomy will be $30 trillion by the end of the decade. One of the instrumental drivers of its rapid growth was the reduction of the cost and turnaround time of DNA sequencing. Reading DNA allowed us to decipher the human genome and paved the way to personalized medicine. It has enabled the design of the COVID-19 vaccine in a record short time and helped us track the emergence of new variants. And now we are witnessing another breakthrough innovation in biology – the ability to write DNA on demand.
Everything the bioeconomy is built on uses DNA, which encodes the genes for the enzymes, proteins, and living organisms used in biotechnology. Those four letters – A, C, T, and G – are the source code for every project, be it biofuels, vaccines and therapeutics, or animal-free meat. Without DNA there is no biotechnology. But the way the business model currently operates is that you have to order DNA sequences from third-party companies like Twist Bioscience, IDT
Telesis Bio (NASDAQ
The other members of the Telesis Bio executive suite have no less impressive resumes. The team of technology innovators is led by the famed gene jockey Dan Gibson, CTO. Dan made his break working for Craig Venter who first sequenced the human genome in 2001. The gold-standard method for putting together long pieces of DNA from many shorter ones 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 a turn-key, end-to-end solution for generating synthetic DNA and mRNA.
The BioXp™ 3200 became the first fully-automated platform that can assemble DNA pieces of several thousand bases long virtually overnight, enabling any lab to become their own gene supplier. But Telesis Bio did not stop there: they tweaked the instrument to expand its capabilities to making mRNA, cloning longer fragments, and performing other synthetic biology tasks in a completely hands-free fashion. Their newest instrument, BioXp™ 9600, has been dubbed “automated synthetic biology workstation” and is poised to expand beyond just DNA assembly and cloning capabilities. With it, scientists will gain the ability to synthesize their own DNA right at the desktop without needing to order custom reagents.
A better way to make DNA
Typically, synthesizing DNA starts out with taking four bottles of chemicals, each corresponding to one of the letters of the genetic code, and joining 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 that Telesis Bio is doing is replacing chemical synthesis with faster and more benign enzyme 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, like Molecular Assemblies, DNA Script, Evonetix, Touchlight Genetics, and Ansa, are also moving into this space. But what sets Telesis Bio apart is that they packaged this technology into a scalable desktop solution. Their BioXp™ 9600 system, which is already available for pharma and biotech customers, will enable companies to become self-sufficient when it comes to DNA synthesis and significantly cut down project timelines.
“A desktop DNA printer will allow you to build any gene, any time, 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 that same day.
Vaccines that can be printed virtually instantaneously
The global gene synthesis market is currently valued at $1.8 billion and estimated to expand at a 17.5% compound annual growth rate. The applications of this technology span various areas of discovery: from vaccines to precision immunotherapy for cancer and antibody therapeutics to engineered meat substitutes and sustainable cellular agriculture products. For all these applications, but especially vaccines and therapeutics, speed is of the essence, 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 next pandemic from emerging by printing out rapid mRNA vaccines. The technology to enable this is not too far out,” thinks Todd.
The company has already partnered with Pfizer
Fighting disease with gene and cell therapies
Another area where rapid DNA synthesis technology can make 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 go after solid tumors. The engineered TCRs target the tumor by recognizing specific markers which make cancer cells different from healthy ones. With the BioXP™ instrument, you can build these TCRs overnight. The faster you can get to the cancer, the better chances you have of survival.
DNA printing could also open up the potential to treat hereditary diseases with gene therapy using gene editing technology CRISPR. CRISPR is already being used for editing the genomes of microbes to produce everything from drugs to materials to chemicals. There are also more than 100 CRISPR gene editing drug trials going on right now. What is required for any gene editing experiment are the guide RNAs which help single out the gene that is being edited. The DBC instrument coupled with SOLA kits would enable gRNA synthesis at the push of a button, which could significantly accelerate progress in these areas.
Being able to store all of the world’s data in a test tube – and more
DNA data storage is another promising area of application for the technology Telesis Bio is developing. Instead of using zeros and ones as the input, DNA data storage uses the four letters of the genetic code to store the information. DNA code has 64 times higher information density and is extremely chemically stable, so every piece of data that we have in the world today could be encoded in DNA, synthesized, and stored in a test tube. Some companies are already switching from digital to DNA: data storage giant Seagate Technology has recently partnered with a startup Catalog to do exactly that. Twist Bioscience, which runs a central service for production of DNA, has partnered with Microsoft
And this is just the beginning. Every other bioeconomy application – from biofuels to cellular agriculture – requires writing DNA. There is limitless potential for companies like Telesis Bio when it comes to enabling innovation: “The BioXP™ is like an iPhone: we’ve built an amazing platform and now it’s all about the applications that you run on it,” Todd predicts.
There are other DNA synthesizers out there, each offering their own spin on the technology. A company called Kilobaser has come out with a desktop DNA and RNA synthesizer, which uses traditional chemical synthesis to print short DNA pieces (called oligos), one at a time. DNA Script has put out a multiplex DNA synthesizer that can print oligos of up to 45 bases and Evonetix is coming out with a desktop machine that enables even longer oligo synthesis. Telesis Bio is looking to expand the current technological capabilities to bring researchers fast, accurate, and multiplex long-fragment DNA synthesis on-demand, coupled with other synthetic biology workflows.
“Telesis Bio is so much more than a DNA synthesis company. We want to empower researchers to become their own service provider with custom-made, highest quality DNA, RNA, and potentially protein,” said Todd. The recent name change from Codex DNA to Telesis Bio reflects the company’s big plans to break out of the existing paradigm of centralized synthesis hubs to allow researchers anywhere to make their own DNA and RNA products.
Thank you to Katia Tarasava for additional research and reporting on this article. I’m the founder of SynBioBeta, and some of the companies that I write about, including Telesis Bio, Twist Bioscience, Molecular Assemblies, and DNA Script, are sponsors of the SynBioBeta conference and weekly digest.
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