Camena Bioscience triggers synthetic biology applications

Synthetic biology company Camena Bioscience has announced a significant breakthrough in DNA synthesis accuracy with the development of an innovative technology called gSynth.

A “pioneering enzymatic de novo synthesis and gene assembly method”, gSynth is able to produce 300 nucleotide DNA molecules with an accuracy as high as 90 per cent.

The Chesterford Research Park company’s CEO and co-founder Steve Harvey, discussing the background to the development, said: “We started in 2016. In the genomics field, there have been huge jumps forward in our ability to read DNA, not least thanks to work done in Cambridge, but there’s never been the equivalent progress in terms of writing DNA.”

With a background as a geneticist and developmental biologist at the National Institute for Medical Research, the Gurdon Institute and the Wellcome Trust Sanger Institute, Dr Harvey knew that the ability to produce synthetic DNA is essential for the investigation and engineering of new biological pathways.

The standard synthesis method, phosphoramidite synthesis, has been the gold-standard DNA synthesis method for many years, but over long stretches of DNA this method is error-prone.

“With phosphoramidite synthesis, the approach is to couple individual nucleotides – bolting together A, T, C and G – was up to 99.6 per cent accurate but the remaining small errors accumulate as synthesis gets longer and in so doing results in an accuracy of just 12.5 per cent success over 300 nucleotides, whereas we can achieve 90 per cent accuracy.

“We took a more modular approach where adding short stretches of nucleotides meant fewer reactions, so we were adding several at one go – three or more. Most people are adding them one at a time, so we’re quite distinct.

“Phosphoramidite synthesis is an organic chemistry technology, where we’ve returned to nature and are using enzymes to bolt together the nucleotides.”

Comparison of several 300 nucleotide fragments found that, on average, 22.7 per cent of phosphoramidite synthesised material was the correct full-length product. However, with gSynth, on average, 85.3 per cent of the material was correct.

Others using enzymatic synthesis technologies include Nuclera Nucleics on the Science Park (developing a DNA printer) and DNA Script in Paris.

“Otherwise no one has taken the approach we have.”

Camena Bioscience has achieved radical nucleotide coupling efficiencies and overcome an additional problem: some sequences, such as stretches of one base (homopolymers), are particularly difficult to produce.

These limitations have been holding back the production of many DNA sequences and consequently new synthetic biology applications.

gSynth demonstrated the greatest improvement of accuracy with sequences containing homopolymers, which are notoriously difficult to produce with phosphoramidite synthesis. In this case just 12.5 per cent of phosphoramidite produced material was correct, compared to 89.2 per cent with gSynth.

This is a significant improvement in accuracy that will be of significance for the development of synthetic biology applications and will help a wide range of markets when it’s officially launched in 2020.

“Our customers are both academia and industry,” says Dr Harvey. “We have an early access programme going on at the moment, with the official product launch early next year. We anticipate that gSynth will affect a wide range of markets from agritech to therapeutics.”

The “early access programme” involves gSynth being effectively beta-tested by interested parties.

“We’re working with a few key opinion leaders.

“It’s a service, people come to us for genes or pieces of DNA that we then make for them at Chesterford Research Park and ship back to them,” Dr Harvey says. “We’re providing a DNA synthesis service to synthetic biologists and because we’re so much more accurate we can help them make things other companies can’t make.

“Things that are really difficult to access in synthetic biology... we’ll be able to give DNA sequences to those biologists.

“They may want to engineer new enzymes to improve industrial chemical processes , or find new ways of making therapeutics – we’re not a therapeutic company, we’re an enabling company, we’re supporting people.”

Expect a funding round soon.

“We’re open for business though gSynth isn’t formally launched until early next year.

“The accuracy of gSynth and our ability to produce complex DNA sequences means that we can offer a premium DNA synthesis service.

“We’re hoping to close a big financial round in the not too distant future.”

Looking ahead to next year, Camena Bioscience looks set to enable a new generation of synthetic biology applications.