Cambridge start-up aims to rewrite the code of life

Scientists in Cambridge have set up an ambitious synthetic biology company which will rewrite the genetic code of bacteria, enabling the microbes to make a vast range of new materials, from drugs to biodegradable plastics.

Constructive Bio, as the start-up is called, is a spinout from the Medical Research Council’s Laboratory of Molecular Biology. A scientific team there led by Jason Chin discovered how to add new chemical letters to the code of life, by which the DNA in genes tells cells to make specific biological molecules.

Reprogramming bacteria in this way could lead to microbial factories capable of making novel materials that are not accessible in other ways. In contrast, the latest “gene editing” methods, such as Crispr, manipulate the existing genetic code but do not create new code.

Following disclosure of the discovery in a scientific paper last year, Chin co-founded Constructive Bio to commercialise it, with a $15mn seed funding round led by Ahren Innovation Capital completed in June. The company has negotiated an exclusive licence with the MRC to exploit its patents on the technology.

Constructive Bio is developing two platform technologies, Chin said. “One is the ability to build a synthetic genome from chemically synthesised DNA, which has broad implications in terms of being able to build organisms that do all sorts of useful things.

“The second is the ability to use these reprogrammed organisms to encode the sequences of completely synthetic polymers, which could be drug-like molecules all the way to new plastics and electronic materials. There are whole classes of new molecules that simply don’t exist today, which would have entirely bespoke and differentiated properties,” he added.

Alice Newcombe-Ellis, founding partner of Ahren, said: “The issue for the company will be what to focus on because there is such a broad, vast market it could go after. The application that I’m most excited about is the ability to programme polymers to be biodegradable. Most of the plastics available today originate from oil and are very hard to degrade.”

Since the dawn of life on Earth, DNA has had four chemical letters — abbreviated to A, T, C and G — which the cell reads in groups of three to make amino acids, building blocks of proteins. But many of these triplets are synonyms, coding for the same amino acid.

Chin and colleagues took advantage of this redundancy in the code, giving some triplets an entirely new meaning while allowing their synonyms to make all the amino acids essential for life.

“By taking inspiration from nature and reimagining what life can become we have the opportunity to build the sustainable industries of the future,” said Chin.

Besides the ability to make new materials, the synthetic bacteria are resistant to viral infection because viruses cannot replicate within cells that have unnatural DNA. This property could also be a big business opportunity for Constructive Bio, said Newcombe-Ellis.

The company’s reprogrammed microbes are based on E. coli, the species used to make many protein drugs including insulin. The bioreactors in which therapeutic proteins are produced today are very susceptible to contamination by phages (bacterial viruses), significantly reducing yield — a problem that could be overcome by incorporating synthetic DNA.

“The dairy industry presents another large potential market because it is particularly affected by the phage problem,” added Ola Wlodek, chief executive of Constructive Bio. The company is setting up labs at Chesterford Research Park outside Cambridge.

Sir Shankar Balasubramanian, professor of medicinal chemistry at Cambridge university, said the company’s technology “allows the exploration of a chemical space in a way that is not possible with existing methods and has truly transformational potential. The development and commercialisation of these technologies at Constructive Bio is incredibly exciting.”