How Is Synthetic Biology Shaping the Future of Drug Discovery?

Scientists are harnessing the power of synthetic biology – a field of science that involves redesigning biological components to generate novel synthetic entities – to solve scientific problems and drive innovation in medicine. Codex DNA aims to help researchers by providing them with the ability to, rapidly and accurately, produce large quantities of synthetic DNA.

Technology Networks recently spoke with Codex DNA’s CEO Todd R. Nelson to learn about the impact synthetic biology techniques are having on pharmaceutical development and the "big trends" in synthetic biology we are already seeing and are expected to see in the next few years. Nelson also discusses the creation of Codex DNA’s synthetic SARS-CoV-2 genome and how this can be used to aid the development of therapeutic and diagnostic strategies against COVID-19.

Laura Lansdowne (LL): How is Codex DNA helping scientists “build biology”?

Todd R. Nelson (TRN): At Codex DNA, we recognize that biologists, especially those that work with DNA, are the new software engineers. By providing easy-to-use products that allow for coding and recoding DNA, we help scientists find new and improved ways to think about how to use DNA to advance drug discovery, vaccine development, and metabolic engineering programs. We help biologists "build biology" by providing new and more effective tools for turning digital information into DNA or proteins, ranging from DNA based vaccines to the ability to store digital information in the strands of DNA.

To meet the ever-increasing demands for printed DNA across the pharmaceutical, biotechnology, vaccine and agricultural markets, we have developed the world's first fully automated DNA printer – the BioXp™ 3250 system. The system helps scientists perform tasks such as the rapid and accurate printing of long stretches of DNA that the instrument then automatically assembles into synthetic genes. When the BioXp™ system takes digital information, like the sequence of a gene, and transforms it into a real-life gene or protein, we build biology. We use our products to do some amazing things like making the world's first SARS-CoV-2 synthetic genome.

LL: How are synthetic biology techniques driving pharmaceutical developments?

TRN: Our products drive significantly enhanced productivity improvements that allow critical path steps in drug discovery to move more quickly. For example, because our products are fully automated and integrated into workflows, we offer the ability to run experiments at a significantly larger scale than has ever been possible. Generally, our products decrease critical timelines and enhance productivity. Because we have the only benchtop solution available, we allow customers to control their workflows rather than spend time and effort working with contract research organizations.

We also have several products, disruptive in nature, that allow for improved results in drug and vaccine development – we say that "what previously took months can now be done in days or hours”. This time-saving is critical for developing certain types of precision therapies such as patient-specific cancer vaccines – our system can facilitate the identification of the "silver bullet" used to treat patients with a personalized anti-cancer vaccine. Our products help these medicines to get to patients faster than ever before and can save lives. A great example of this is our collaborative work with Dr Stephen Shoenberger, a world-renowned immunologist, who has used the system to identify critical personalized cancer vaccines.

LL: Could you tell us more about the world's first full-length, synthetic SARS-CoV-2 genome, and how this can help to develop vaccines, therapeutics and diagnostics against COVID-19?

TRN: Using the BioXp™ system, we generated the world's first fully synthetic genome for the COVID-19 virus in an unprecedented ten days. The genome – a collection of the COVID-19 virus genes – is now being broadly used across the pharmaceutical, vaccine and diagnostics industries. The best way to think about it is that we created a highly flexible template consisting of the virus’ genes that can be diversely implemented for research. For vaccine development, companies use the template to identify the optimal "active ingredient" for COVID-19 vaccines to generate the best immune response once given to humans. For the development of therapeutics, researchers use the template to create antibody-based drugs referred to as biologics. The diagnostics industry uses the genome to identify regions of the genome that can be used for rapid testing.

Molly Campbell (MC): A key application of synthetic biology is metabolic engineering. Can you talk to us about the latest developments in this field and the technological advances that have enabled them?

TRN: Multiple disciplines have converged to understand how complex biological systems function. The significant technological advancements from these efforts have spanned the entire "design-build-test cycle”. Improvements in DNA sequencing and bioinformatics tools enable accurate annotation of genes and pathways to identify ideal hosts as starting points for performing metabolic engineering. Through decreasing costs and increasing the capacity to perform large-scale gene, gene pathway and genome construction, even simple cloning or mutagenesis manipulations can now be performed as de novo syntheses. The development of assays that rapidly report a readout for a given gene sequence has also expanded throughput.

In addition, artificial intelligence algorithms permit a more accurate prediction of enzyme and pathway function in a defined cellular environment. Finally, genome editing tools, such as CRISPR/Cas9, have enabled the precise editing of any genome at any location, especially the deletion, addition or substitution of naturally occurring DNA sequences with libraries of small or large synthetic DNA constructs. All these advances, combined with the capacity to synthesize libraries of genes and pathways at a large scale, have opened the door to testing millions of gene sequence permutations simultaneously.

MC: What are some of the key challenges in progressing synthetic biology research from the laboratory to the clinic?

TRN: One of the challenges we face in synthetic biology is working with the US Food and Drug Administration (FDA) and other regulatory agencies. We are all working towards a better understanding of the safety criteria needed to develop and manufacture a product, perhaps at point-of-care (POC), and administer to a patient as a therapy or a vaccine. The impact of synthetic biology is already being seen within the drug discovery industry and drugs that have been discovered and developed using these technologies and applications are already well advanced.

MC: In your opinion, what do you see as being the "big trends" in synthetic biology right now, and what do you envision the field will look like in 10 years' time? 

TRN: That's a great question. For the next few years, the ability to rapidly and accurately produce DNA will continue to create strong demand in drug discovery to identify safer, more effective drugs and vaccines for both cancer and infectious diseases.

That said, we are currently working on commercializing – within 18 to 24 months – a fully automated vaccine printer referred to as the DBC or "Digital-to-biological converter”. The idea here is that we can use the technology to stamp out future pandemics like COVID-19 by placing a vaccine printer in hospitals, or even in your local pharmacy. When you consider having a global network of these vaccine printers available, it is easy to imagine a world capable of responding to pandemics with unprecedented speed. Once the desired viral sequence is known, in minutes, we can initiate the printing of vaccines anywhere in the world, with the push of a button, containing outbreaks within a zip code.

Longer term, we are very excited about the ability to store digital information in strands of DNA. This emerging field of DNA digital storage has tremendous potential because DNA is an ideal data storage solution. It is small, extremely dense and can last for millions of years – think Jurassic Park. It is quite impressive, really; if stored as strands of DNA, all the content ever created on Facebook would fit into a small tube the size of your fingertip.

Codex DNA has made significant progress in this field by creating a prototype instrument that can translate binary code into the letters of DNA, creating print-ready files. The information in these files, whether it's text (Library of Congress), audio (Spotify), or video (Netflix), can be printed and assembled into strands of DNA that can be decoded back to its original format using existing technology. The biggest challenge here is the printing and retrieval speed, which we are working on right now.

Todd R. Nelson was speaking with Molly Campbell and Laura Elizabeth Lansdowne, Science Writers for Technology Networks.