From engineering single enzymes to creating cascades that reconstitute metabolism ex vivo, technology has enabled biopharma to make giant leaps in the past decade. What is the state of synthetic biology in biopharma production today, and what does the future hold?
Inscripta President and CEO Sri Kosaraju quizzed a panel of experts about the topic at the SynBioBeta Synthetic Biology Biopharma Conference 2021.
Grant Murphy, director of protein engineering at Merck, told the panel about his work developing enzymes to replace chemistries that may be synthetically challenging, costly, or not aligned with the principles of green design. What was previously done one enzyme at a time, can now be scaled to cascades of enzymes.
A big aspect of biopharma is reverse engineering biology to understand how to impact it with pharmaceuticals. Synthetic biology and the ability to do high-throughput multiplexing experiments will allow to accelerate target validation and delve deeper into off-target binding and other unresolved issues in pharmaceutical R&D.
The future lies with forward engineering, he added, and emerging fields like protein design will likely lead the way: “We’re no longer going to be constrained to the antibodies or therapeutic enzymes that Mother Nature gives us – we’ll be creating those de novo. When we start building our own biological machines, we really have a new frontier.”
Overcoming challenges in drug discovery, development and manufacturing
The panel reflected on what aspects of the process could be improved to drive forward innovation in the biopharmaceutical industry. One theme that emerged is that the complexity of biology makes discovering new therapeutics or vaccines challenging.
“The underlying biology, which runs on a digital code, is still hard to work with,” said Barry Canton, Chief Technical Officer of Ginkgo Bioworks. “We’re getting better, but we could be much, much better.”
He went on to describe the set of technological improvements that have the potential to advance the pace of innovation, from DNA writing and editing to computational algorithms for protein structure prediction.
“One of the things that I think is exciting about what Inscripta is doing and the OnyxTM system and that whole category of other companies: you are building and developing tools that are specifically for doing synthetic biology, making it easier to engineer cells, manipulate them,” commented Canton. “Advanced technologies for this specific purpose will help all of us advance projects faster, reduce budgets and succeed in more projects every year.”
For Chris Savile, Chief Operations Officer at Willow Biosciences, the benefits of Inscripta’s technology lie in enabling new business opportunities. “Strain engineering used to have this huge barrier to entry, huge upfront investment, long timelines, and it really gave you a limited set of opportunities to go after,” he said.
“Being able to go off-pathway and alleviate some of the bottlenecks that are difficult to rationalize is where the Onyx system is directly applicable,” said Savile. “The greatest benefit is being able to do that in the right context – we can make edits now on your commercially-relevant strain or production strain and immediately get that tested, validated and scaled quickly and not have to rely on plasmid systems and other reporter strains that may not translate. Reduction of that development time is what makes it so powerful.”
Working directly on the commercially relevant production strains has helped shorten the development cycle timeframe by about 40 percent for his company’s synthetic cannabinoid products.
Creating new opportunities – and ensuring they are accessible to all
During the live Q&A session, the audience asked follow-up questions about the biggest industry opportunities and gaps. Chris Savile of Willow Biosciences restated the importance of making genome editing more accessible.
“Synthetic biology is inherently democratizing,” noted Chris. Removing barriers to access of information and technologies will be the catalyst for success, as it promotes new collaboration and data sharing opportunities.
“As our capabilities grow, so will the information we derive,” Grant Murphy seconded, talking about advancing our understanding of phenotypes and the underlying cell biology. “Hopefully we can create an ecosystem where that information is something that is accessible and shared as a pre-competitive resource for biopharma and synthetic biology in general.”
Sri Kosaraju closed the session with a perspective on the iterative nature of innovation, where progress made in one technological area catalyzes advances in the other aspects of the cycle. “There are some really impactful products that can be developed, and today, even though the tools are better, the tools don’t enable us to get there. So, the first place to start is with the tools, and then – how do we put it all together in the right way? That’s where collaboration comes in.”
To delve into the specifics of this insightful discussion, watch a replay of the panel here.