Current and Future Impact of Synthetic Biology

The field of synthetic biology, involving the development of novel artificial biological pathways, organisms, and devices as well as the redesign of pre-existing natural biological systems, is evolving at an ever-faster pace. Since its development was first enabled in the 1990s,¹ it has been associated with some of the most important topics in life sciences research—including the fight against COVID-19.²

The economic impact of the sector is also growing in its importance, with the global market size increasing from US$9.5 billion in 2021 to an estimated $33.2 billion by 2026.³ Recognizing the growth and potential of this field, this article explores some of the most innovative trends, companies, and technologies in the sector, along with expert perspectives for the future.

“Synthetic biology is about tools and mindset. Fundamentally, which tools and technologies can we use to reprogram living systems (like bacteria or mammalian cells), and how can we employ these technologies for sustainability and human health?” asks Fiona Mischel, Director of International Outreach at international industry trade group SynBioBeta. “The tools aren't the full picture, of course, but they provide a strong starting point. I believe the field is rooted in leveraging new technologies that benefit the health of people and the planet.”

When it comes to microorganisms such as bacteria, the concept of community is key—from maintaining a healthy gut through to ensuring clean water and bioactive soils. Dr. Christian Roghi, Director of Microbiome Solutions at Eagle Genomics, thinks that they hold a lot of potential. “These mixed microbial communities (microbiomes) do not reflect a randomized individual mix, but an interacting microbiological entity. For over a century, harnessing their value has been limited and utilized predominantly in wastewater treatment,” he shares. “This has been achieved by manipulating the microbial environment to create a defined function.” While such selection-based approaches have proven to be invaluable for guiding initial bioprocess, they have limitations and certainly do not unlock the full potential of these microbiomes. “Moving forward,” he says, “we need to take a bottom-up, parts-based engineering approach to create genetically modified microbiomes with more refined metabolic activities. Eagle Genomics, via its AI-augmented knowledge discovery platform, e[datascientist], is helping to unleash the power of microbial communities to help solve current and future challenges.”

The influence of synthetic biology via microorganism-based systems such as the microbiome is vast. However, when turning the synthetic biology lens to human DNA, the potential to accelerate R&D and human health is also significant. A big recent breakthrough, for example, has been DeepMind’s AI software AlphaFold, which is focused on predicting protein shape based on its amino acid sequence.⁴ “At the very least, AlphaFold gives us a better understanding of how proteins function and reveals potential new drug targets, binding sites, and all kinds of potential protein interactions we weren't able to explore before,” comments Mischel. “This has huge implications for human health, including novel drug discovery and development.”

Twist Bioscience’s synthetic DNA creates high-quality antibody libraries for a range of organizations carrying out vital R&D. Such libraries could lead to more efficient screenings, and therefore be a game-changer in the drug development industry. “By leveraging our unique ability to manufacture DNA at scale, we can construct specific antibody libraries designed to match sequences that occur naturally in the human body, pan them to find hits, and optimize them to get highly potent leads that are ready for preclinical development,” Co-Founder and CEO Emily Leproust, Ph.D., explains. “The core of our DNA synthesis platform is a silicon chip that enables us to ‘write’ one million oligos at a time, compared to legacy approaches that use a 96-well plate to make 96 oligos at once. This allows us to manufacture DNA at a scale otherwise unavailable for customers. This approach is also more sustainable. We’ve miniaturized the chemical process of synthesizing DNA and use 99.8% less chemical reagents than approaches that use a 96–well plate,” she says.

Synthetic biology has also been making a significant impact on the world of mammalian cells and their potential applications, in the research lab as well as in a clinical setting. A strong example of this is cell coding company bit.bio, which "engineers biology" through its cell identity coding platform. “In principle, bacterial and mammalian systems are very similar, in that they have three things in common: we can read both their genomes, write onto their genomes (for example, through CRISPR-Cas9 technology), and also execute their 'programs', i.e., their genetic codes or genomes. Life essentially runs its own software script, encoded in DNA, which is transcribed and translated,” says Dr. Mark Kotter, Founder and CEO of bit.bio. “Our focus is on programming at the information layer of the cell via the genome, with our precision cellular reprogramming technology, opti-ox.”

opti-ox technology, a core part of the company's cell identity coding platform, overcomes a common issue called gene-silencing, by "hacking DNA". “Often the cell understands that a gene or transgene that is at odds with the current state is being activated. Its natural response is to silence it down again. To do that, cells have developed many different mechanisms and many of those are not yet fully understood by the scientific community.” bit.bio’s goal is to continue to develop and apply its technology to human health: “This would allow us to program cells so that they display a consistency in the manufacturing process, which in turn, could help to set a standard and open up new avenues for research and drug discovery,” he adds. The possible applications are almost limitless, Kotter highlights: “It could be instrumental in the manufacturing of cell lines for gene therapy, or in the production of RNA—really, it could be used to produce every human cell, with every cell being a potential medicine—delivering significant impact for human health and beyond.” The company already has multiple human cell products and disease models on the market that are powered by opti-ox technology. A pipeline of cell therapies is also in the works.

With so many exciting technologies currently being developed and used in synthetic biology, the future could not look less thrilling. Roghi explains the future potential of the microbiome: “Creation of systematic design of ‘designer microbiomes’ requires the convergence of automation, genome editing, high-throughput bioanalysis, and machine learning to rapidly develop and test microbiomes for specific capabilities through iterative design-build-test-learn cycles. This approach requires a strategic and collaborative effort due to the enormous complexity of the microbial interactions and the poor characterization of the vast majority of microbes, where such information is needed to enable the precise engineering of microbiomes for biomanufacturing, resource recovery, and other applications. Enabling better understanding of microbiome data and being able to derive insights not normally seen by humans, is one positive step in this exciting direction.”

From Mischel’s perspective, she sees the influence of a field that has greatly benefitted from the studies done in the fight against COVID-19—mRNA. “I would expect to see a lot more mRNA platforms (including for CRISPR delivery) and RNA and DNA vaccines.”

Other directions include the personalization of medicine and next-generation sequencing (NGS), as Leproust notes: “Many therapies will need to be developed to treat each patient’s unique form of cancer or other diseases. With synthetic biology tools, researchers can produce thousands of antibody clones per experiment, giving them more options to develop targeted therapies for patients. NGS tools can be used to identify genetic areas of interest and monitor for minimal residual disease after treatment.”

Kotter outlines the opportunity of creating multi-functional cells: “The traits of different cell types can be combined to make cells that don't actually exist in nature, and which have very specific properties. A current example that I am aware of is T cells that share characteristics with macrophages.” The improvements in this sector, he states, are connected to the area of regenerative medicine. “The possibility of looking up at every single cell as a possible medicine really opens up many more opportunities in regenerative medicine as well. Researchers have been working on solutions for the past 30 years to replace organs, or to protect them from aging and disease, but traditional biology has not as yet been able to deliver many viable outcomes. With technologies such as ours at the forefront of science, I anticipate that in the next 20 years or so, we’re going to completely change the way in which we approach such challenges.”

References

1. Cameron, D. Ewen, Caleb J. Bashor, and James J. Collins. "A brief history of synthetic biology." Nature Reviews Microbiology 12.5 (2014): 381-390.

2. Bruynseels, Koen. "Responsible innovation in synthetic biology in response to COVID-19: the role of data positionality." Ethics and Information Technology 23.1 (2021): 117-125.

3. https://www.bccresearch.com/market-research/biotechnology/synthetic-biology-global-markets.html

4. https://alphafold.ebi.ac.uk/