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The Lowdown on Constructive Biology

By John Danner, CEO Codon Devices

August 8, 2007 | Codon Devices is an early commercial pioneer in the emerging field of synthetic biology. CEO John Danner points to a paradigm shift occurring in what he terms “constructive biology.” Laurie Sullivan, an editor at CHI’s  PharmaWeek newsletter, asked Danner about the next wave of innovation in biotechnology.

Q: What do you mean by “constructive biology”?
: Constructive biology simply refers to Codon Devices’ massively industrialized, synthetic approach. Using our BioFAB production platform, we’ll be able to make genetic constructs so quickly and cheaply that it will essentially allow all biotechnology research to begin with constructing an engineered genetic device, to either test it for functionality or to develop it into a product.

Is constructive biology synonymous with synthetic biology?
: The synthetic biology industry has been around for a few years but has always been too expensive and too slow to really be able to impact mainline biotechnology applications. Constructive biology is a vision we have at Codon Devices that would render these synthetic approaches in a highly industrialized version. Through our proprietary technology, we’ll be able to lower prices and reduce turnaround times, enabling us to deliver synthetic capabilities to the industry and make them ubiquitous throughout biotechnology. For example, replacing DNA cloning-based molecular biology with synthetic-based, rapid-evolution platforms and engineering platforms to optimize genetic constructs for protein-engineering and metabolic-engineering applications.

What applications of constructive biology are Codon Devices interested in?
:  There are many. Starting with the molecular biology space, for example, introduction of an engineering toolkit would enable molecular biologists to test sets and be able to do iterative testing in a much more designed and discrete way. That would effectively change the workflow of molecular biology. And from that, constructive biology could be powerful in engineering therapeutics, or rapidly developing vaccines against potential outbreaks or biothreats.

There are also many applications across the biofuels space, for example using pathway engineering to design cellular performance to enable more effective fermentation of bioethanol sugars into ethanol fuel. In the agricultural space, through multi-trait engineering we could design specific agricultural traits into crops or renewable energy feedstocks.

What implications does constructive biology have for the therapeutic space?
: The concrete opportunity for the therapeutic space is within protein therapeutics. Having such powerful tools to streamline development, lower costs, and reduce uncertainty can massively improve the productivity of protein therapeutic development.

What are some of your challenges?
: The technology is so powerful that it’s applicable in many different industries. A great challenge is being able to deploy the technology in the highest-value way, where it can make the most impact the most quickly. Being able to do that, in the reality of partnering with other companies from multiple industries, is probably the most immediate practical challenge we face.

Are there any other companies doing similar work to yours?
: No, but there are predecessor technologies that have done evolution in ways that are different from ours. There was a series of technologies several years ago using DNA shuffling technology, where essentially the creation of random diversity around a target construct was used to find a variation of the target construct with better functionality.

We believe that in many ways, a constructive biology approach is superior. We can deliver that same diversity, but it can be designed diversity versus random diversity.

We only build what we want. So we can impart sequence-level characteristics that are known to improve the functionality we are trying to improve, and we can remove sequence-level characteristics that are known to be detrimental to the functional performance we are trying to optimize. Designed diversity is, we think, a whole generation of technology beyond random diversity.

What are next steps for Codon Devices?
: We are actively engaged in developing partnerships, in many cases with therapeutic companies that are trying to quickly and cost-effectively evolve antibodies or other protein therapeutics across multiple functional parameters. We believe our approach will help potential partners really leapfrog how they do protein therapeutic development today.

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