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BCC Research podcast recap: Codex DNA on the future of synthetic biology

May 12, 2021  |  Codex DNA

BCC sits down with Jason Lehmann, PhD, from Codex DNA, Inc. in San Diego to talk about Codex DNA’s mission of applying breakthroughs in synthetic biology automation solutions. BCC podcast host Clara Mouawad and Jason talk about Codex DNA’s recent initiatives in DNA, RNA, and protein synthesis — and how this aligns with creating sustainable healthcare and technology solutions for some of humanity’s biggest challenges.

BCC: Can you tell us a bit about yourself and how you came to Codex DNA?

Jason L: I am one of the product marketing managers here at Codex DNA. I did my doctoral training in the Biomedical Sciences graduate program at UC San Diego. I was a program mentee for a genetics and genomics training grant, and my dissertation work leveraged comparative genomic data to investigate what makes certain species of bacteria pathogenic while others are not.

From there I moved to the University of Florida for a postdoctoral fellowship investigating adaptive immunology in asymptomatic malaria patients in rural Haiti.

I’ve been doing product marketing in the San Diego biotech sector ever since, and just recently had the opportunity to join Codex DNA. The team here is doing some exceptionally exciting things within the synthetic biology space that I’m really excited to talk with you about today.

BCC: Your mission is as ambitious as it is exciting; “Codex DNA is attempting nothing less than building biology and changing everything.” Can you expand on what that means?

Jason L: Our mission is to apply our breakthroughs in automation solutions for DNA, RNA, and protein synthesis in order to enable customers to program and “write” synthetic biology and to create sustainable healthcare and technology solutions for some of humanity’s biggest challenges.

Codex DNA products are radically transforming rapid demand and response workflows by consolidating supply chains and enabling globally distributed manufacturing in terms of both discovery and clinical applications.

Our gene synthesis portfolio reduces the turnaround time for synthetic biology workflows from weeks and months to days and hours, and includes the BioXp™ system, biofoundry services, and our benchtop Gibson Assembly® reagents.

In addition to accelerating and optimizing automated DNA design in areas such as synthesis, cloning, and amplification, Codex DNA and the BioXp™ system ensure that researchers’ designs stay in their hands, marrying speed and security for innovators in drug discovery, vaccine  development, precision medicine, and beyond.

BCC: Zooming in, Codex DNA just released the first synthetic genomes on two COVID-19 variants. What  does that mean and why is this such an exciting development?

Jason L: Codex DNA’s core technology was originally developed for pandemic preparedness applications, which enabled our team to pivot very quickly to helping researchers battle COVID-19. As a result, we successfully created the first full-length SARS-CoV-2 synthetic genome de novo in April 2020 using our BioXp™ synthetic biology workstation.

Since then, our full-length SARS-CoV-2 synthetic genomes have been widely adopted and used to develop various preventive and treatment measures.

There is scientific data coming out of recent studies assessing mutational changes in the spike protein of emerging SARS-CoV-2 variants, suggesting that these new variants could potentially evade the protective effects of antibody therapies and vaccines.

To enable researchers to address these new threats, we have released three additional synthetic genomes of the emerging UK, South Africa, and Brazil P1 variants of SARS-CoV-2 in order to help accelerate therapeutic development.

Our customers are using these full-length genomes for new therapeutic discovery and validation, as well as in high-throughput virology screening assays that model COVID-19 infections. We believe these synthetic genomes will also be key in tracking the spread of the new and emerging variants across the globe through their use as diagnostic controls.

Listeners interested in hearing more about real life examples of how Codex DNA’s technology is being used to combat emerging SARS-CoV-2 variants can visit our website to view a webinar we hosted with Dr. Jesse Erasmus from the University of Washington, who discusses his progress in developing a self-replicating RNA vaccine platform against the disease.

BCC: Talk to us about the process. The result is genomes that do not require additional processing steps. How does that work, and how does it differentiate you from others in the field?

Jason L: The BioXp™ 3250 system enabled us to build the entire genome of SARS-CoV-2 from design to final assembly. Codex DNA was the first to market with in vitro transcription-ready genomic material from the virus.

Our proprietary design tools were employed to create an in silico map of the hierarchical three-stage assembly that was necessary to build the SARS-CoV-2 genome.

From there, we loaded the reagents onto the BioXp™ system and executed the run. Using Gibson Assembly® technology, originally developed by Codex DNA’s Chief Technology Officer Dan Gibson, a series of hierarchical fragment assemblies enabled our scientists to clone an entire viral genome that arrives ready for downstream applications.

Synthetic genomes are a much more reliable and scalable source of viruses than clinical samples since clinical samples, when propagated extensively, often result in a mixture of virus population with multiple genomic changes. Synthetic genomes can be reliably used to generate viruses that can be tested against vaccine and therapeutic candidates.

BCC: Clearly COVID-19 has had an impact on the work you are doing. In what other ways has the pandemic influenced the direction of your work?

Jason L: Since the start of the COVID-19 pandemic, the Codex DNA team has been working hard to ensure that our customers have access to the tools they need to combat this global public health crisis.

We also established our biofoundry services last year to support our customers. These services enable customers to order any of the BioXp™ system products like synthetic genes, clones, cell-free, amplified DNA, and variant libraries, and have Codex DNA’s team build and ship them to their labs.

This was a big help to researchers who were eager to get to work combating the pandemic, but whose labs had been closed due to COVID-19 public health concerns. By the time the researchers were able to get back to work, we were ready to ship them the tools they needed — without any lost time.

We also continue to partner with our customers to identify future products and services we can build or provide to help in their fight against COVID-19.

BCC: How do you see the focus on synthetic genomes and vaccine and therapeutic development changing post-pandemic?

Jason L: We believe that synthetic genomes will continue to be very powerful research tools for fighting future epidemic health crises.

Synthetic genomes enable researchers to safely study pandemic-causing pathogens and develop therapies and diagnostics without needing the highly regulated biosecurity facilities typically required for studying such dangerous microbes. Removing this restriction can greatly facilitate vaccine research and development across multiple infectious disease programs.

Specifically, Codex DNA’s offering of full-length genomes, genome derivatives, and replicons with reporters will continue to be used to generate recombinant viruses and pseudo-typed virus particles. These reverse genetics systems enable the study of viral pathogenesis and the development of assays to test candidate therapeutics and vaccine efficacy, and — importantly — they allow scientists to focus on the strain most relevant to their experimental needs.

As new diseases and their variants spread, it is essential for scientists to rapidly adapt their research programs to address these emerging threats. The ability to rapidly design, build, and test these emerging variant genomes is directly applicable to these efforts.

Additionally, the use of mRNA as a vaccine platform has gained a lot of momentum this year, and we expect it to be a major tool in development of future infectious disease and cancer vaccines moving forward.

Codex DNA, by taking advantage of the rapid-iteration capabilities offered through our BioXp™ system and library kits, and soon the ability for synthetic mRNA production, will continue to provide new full-length genome tools to support researchers worldwide in their fight against future pandemics.

BCC: Talk to us about Codex DNA’s BioXp™ 3250 system. It’s the first and currently only hands-free and fully automated synthetic biology platform. What does that allow you to achieve?

Jason L: The BioXp™ 3250 instrument enables numerous synthetic biology workflows by providing a hands-free, end-to-end solution for generating synthetic DNA and mRNA starting from a DNA sequence.

Gene sequences can be assembled, cloned, and amplified into user-specified vectors in a single overnight run.

The system allows researchers to improve productivity, reduce turnaround times, increase throughput and scale, enhance quality, and retain complete workflow control for both synthetic DNA and mRNA formats.

By accelerating the design-build-test phases of product development cycles, the BioXp™ 3250 system can increase productivity 20- to 50-fold and drive advances in the fields of personalized medicine, biologics drug discovery, vaccine development, genome editing, and cell and gene therapy.

BCC: Looking to the future, what do you foresee happening in the world of synthetic biology in 10 to 15 years?

Jason L: Within the next 10 to 15 years, we expect that synthetic biology will radically transform the medicines we develop, the food we grow and eat, and even how we produce biofuels and renewable energy from engineered microbes.

New markets for synthetic biology applications are rapidly emerging. This expansion is being driven by continued innovation, a deepening understanding of biology, and growing access to novel research tools.

The key areas we expect to see continued growth include therapeutics and vaccines discovery, agriculture, and multiple consumer markets including creating plastics from biodegradable polymers, and enhanced data storage methods.

Already, synthetic biology is being used to discover, develop, and produce novel DNA-, mRNA- and protein-based therapeutics and vaccines. Examples here include antibody-based biologics, the mRNA-based COVID-19 vaccines, and personalized cancer therapeutics.

In agriculture, synthetic biology will continue to be used to improve crop yields and create novel food sources. A good example of something already taking place in this space would be the recent commercialization of plant-based substitutes for meat products.

Finally, in technology, synthetic biology may lead to the ability to store and retrieve digital data using DNA. This technology is in its infancy, but to give you an example, it was reported in 2019 that the entirety of the English-language version of Wikipedia had been digitally encoded into synthetic DNA.

Overall, we will continue to see synthetic biology products and inventions permeate society over the next 15 years such that by that time nearly everyone will have either used, consumed, or received medical care with one.

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