One of the important figures behind deoxyribonucleic acid (DNA) synthesis technology is biochemist and Nobel Laureate Kary Mullis. Allegedly, he discovered a way to synthetically replicate DNA through what is now known as polymerase chain reaction (PCR) while dropping massive hits of acid on his way home from work. And despite the massive potential behind PCR, he instead went on start a company that sells jewelry containing the amplified DNA of dead famous celebrities like Marilyn Monroe and Elvis Presley.

Fortunately, other, more business-savvy folks have realized DNA and ribonucleic acid (RNA) synthesis can be used for more important applications. Since Mullis’ discovery, replicating DNA and RNA from a template, like from the nucleus of an organism, has been relatively straightforward. Pretty much like copy and paste for code – no thinking required. The big challenge (and opportunity) has been learning how to design new DNA sequences and essentially rewrite the code of life. The state-of-the-art used to be using chemical synthesis to construct DNA bases one by one, in the same way that pharmaceutical drugs are produced, which was extremely costly, laborious, and toxic.

DNA and RNA Synthesis as a Service Versus Hardware

Nowadays, companies are jumping on the enzyme bandwagon, which has accelerated and expanded the technological possibilities, to construct DNA and RNA sequences on demand for therapeutics, vaccines, and research. We recently covered Codex DNA (DNAY), a newly public company that has developed is a desktop machine that creates DNA – from the digital DNA code to an actual strand of DNA. We were originally interested in Codex DNA because we’re investors in Twist Bioscience (TWST), which provides DNA synthesis as a service. If companies like Codex DNA can put easy-to-use tools into the hands of customers, what will that do to those firms offering DNA synthesis as a service?

In its SEC filing, Codex DNA listed some of its prime competitors. We culled the list down to those offering DNA synthesis as a service or developing hardware for on-demand production anywhere. Here are seven companies doing DNA synthesis for more than just making jewelry from the dead.

DNA Synthesis as a Service

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Nutcracker Therapeutics out of the San Francisco area was founded in 2018 to design mRNA therapeutics and vaccines. It has raised $74 million after a $60 million Series B that closed in September 2020. The company is developing a computer-controlled RNA manufacturing system called Automated Controlled RNA (ACORN). The platform relies on disposable microfluidic “biochips” that allow nucleic acids to be produced and encapsulated directly without any contamination, taking a page out of the semiconductor manufacturing industry. These nanoparticle-encapsulated mRNA are ready to go and can be used for research or patient treatments. The company is putting its initial attention on mRNA therapeutics for treating cancers, with plans on expanding into other diseases. We can’t wait for the money-making vaccine for erectile dysfunction.

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Aldevron is based in Fargo, North Dakota, where they can store mRNA vaccine outdoors in the winter. Founded in 1998, news just hit that Danaher Corporation (DHR) is acquiring the private company for $9.6 billion to slot into its life sciences division. The company manufactures plasmid DNA, mRNA, and recombinant proteins, which are the necessary ingredients for designing nucleic acid-based vaccines. Aldevron offers contract manufacturing for custom nucleic acid and protein production and provides its own biologics for sale.

Aldevron - Core Products
Credit: Aldevron

Aldevron is currently collaborating with Moderna on its COVID-19 vaccine program, with plans to expand their existing partnership to include other programs in Moderna’s clinical development pipeline.

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Founded in 2013, San Diego-based Molecular Assemblies is a biotech startup that’s designing DNA synthesis technologies. It has raised $30.8 million after a Series A that closed in April 2021 with investment from the likes of Agilent Technologies (A). Molecular Assemblies has developed a three-step enzymatic process for constructing longer synthetic oligos. The startup wants to target all the potential markets and applications for DNA, including agriculture, biofuels, DNA information storage, nanoscale DNA, genetic electronics, and therapeutics. The company is working with GE (GE) Research to enable the production of nucleic acid-based vaccines and therapeutics.

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Founded in 2002, GenScript Biotech (GNNSF) is headquartered in New Jersey but trades on the Hong Kong exchange. Its services include DNA synthesis by providing genetic and protein materials for laboratories, such as research reagents for better understanding the COVID-19 virus. GenScript Biotech offers custom-modified DNA and RNA short and mediums strands, known as oligos, which is shorthand for oligonucleotides.

GenScript Biotech - GenBrick Synthesis Service
The GenBrick Synthesis Service. Credit: GenScript Biotech

These products are provided as natural, unmodified
strands or can be modified to be labeled with fluorescent dyes that help
researchers and laboratories identify sequences in DNA for genetic testing and personalized
medicine. The company uses an electrochemical oligos synthesizer platform, which
we don’t quite understand but sounds good to us, that can construct customized
pools of DNA or RNA for less than $0.02 per base pair. Any time you can drop
the cost of an expensive process in biotech, you know there’s a potential market
opportunity.

Hardware for DNA Synthesis

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Founded in 2014, DNA Script is a French DNA synthesis startup that has brought in $112.6 million in funding after a Series B round that closed in July 2020. The company has designed Syntax, a benchtop DNA printer that produces synthetic DNA oligos on demand. Much like how 3D printing was meant to make home and small business manufacturing of complex instruments, materials, and devices into a routine process, a benchtop DNA printer would help researchers and laboratories accelerate research by reducing the lag time and costs of waiting for samples from custom oligos fabricators.

DNA Script - Syntax Benchtop DNA Printer
The Syntax Benchtop DNA Printer. Credit: DNA Script

The printer can synthesize up to 96 oligos between six and 13 hours, depending on the length.  The startup is working with diagnostic assay developers to design tools that help researchers dig deeper into important scientific questions, like how to treat baldness.

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Founded in 2013, Nuclera Nucleics is a biotech company headquartered in the United Kingdom that has pulled in $11.3 million following a Series A that closed in November 2018. Nuclera Nucleics is also developing a desktop bioprinter for designing custom proteins and genes that will allow researchers to construct any biological product they want within days. The system relies on enzymes that can quickly and selectively link together nucleotides into nucleic acids.

Nuclera Nucleics - DNA Bioprinter
Nuclera Desktop Bioprinter. Credit: Nuclera Nucleics

The company recently acquired the microfluidics unit of E Ink, an electronic ink manufacturer, to expand the intellectual property needed to design its desktop bioprinter. The combined technology will rely on digital microfluidics, where electric signals are used to guide microdroplets rather than conventional channels.

Founded in 2000, CureVac (CVAC) is an $11 billion German biopharmaceutical company betting big on the mRNA vaccine technology behind the Prizer/BioNTech and Moderna (MRNA) COVID-19 vaccine programs. The firm has its own in-house nucleotide sequence library that enables it to assemble the various pieces of mRNA into the desired therapeutic without doing additional chemical modifications in the RNA. It is also developing a portable mRNA “printing” facility called, creatively enough, RNA Printer, which can be stationed in hospitals to provide personalized medicine or to respond to, say, a pandemic.

CureVac - Coronavirus Vaccine
Credit: CureVac

Speaking of which, CureVac is also pumping out a series of its own mRNA vaccines, including COVID-19 mRNA vaccine at clinical phase 3. It has also been busy designing mRNA vaccines for rabies (currently in clinical phase 1), yellow fever, malaria, influenza, lung cancer, and skin cancer. CureVac has partnerships with Bayer (BAYRY), GlaxoSmithKline (GSK), and the Bill & Melinda Gates Foundation. The company is also working with the likes of Harvard, Yale, and Crispr Therapeutics (CRSP), a gene-editing company, on protein-based therapies using its mRNA technology to construct functional, customized proteins.

Conclusion

COVID-19 has been a major accelerator for the advancement of DNA and RNA-based vaccine technology. That means the next wave of biotech companies are going to be looking for other ways they can plug mRNA vaccines into the therapeutic pipeline of other diseases and conditions. We’re talking about the platforms to reprogram cells to do our bidding. Combined with CRISPR gene editing and other technologies in the synthetic biology space, customized DNA and RNA synthesis, and all the ingredients that go into them, will definitely be a big player in the future of therapeutics.

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