A different approach: reimagining biology

Evonetix is reimaging biology by developing a different approach to gene synthesis. Three key members of the team – Dr Raquel Sanches-Kuiper, Vice President of Technology, Dr Matthew Hayes, Chief Technology Officer and John Edgell, Head of Cloud Engineering – explain how the company is doing this and what it means for the advancement of DNA synthesis in the lab.

Dr Matthew Hayes, Chief Technology Officer, was a founding member of the team that established Evonetix in 2015. “Before starting Evonetix, I had been working on a thermocycling technology for medical diagnostics systems and had been looking at the potential for heat control in DNA synthesis using modified phosphoramidites with a thermal, rather than acid, based deprotection step to control the synthesis cycle. I began exploring array-based technology for highly parallel DNA synthesis and whether this could be achieved using multiple heater/cooler synthesis sites to overcome some of the challenges faced by traditional array-based DNA synthesis platforms. After some calculations on a whiteboard, I realised that it is controllable and within the laws of physics – it was just an engineering challenge.

“I’d had experience in semiconductor technology and chip design from my work with Cambridge Consultants and could see how the scalability of silicon chip manufacture would allow DNA synthesis, only currently available from dedicated service centres, to be available in a benchtop system.

This inspired the core idea and we started the early stage of the company with seed money from Hermann Hauser and Cambridge Consultants. With a team of around six engineers and six chemists, we spent the next 18 months developing the first chips

“Since then, we’ve raised series A and B funding, expanded the team to over 100 people, and have been working to combine all the separate elements of our technology to synthesise DNA on the surface of our chips.” The result is a platform that has been designed from the ground up to be a benchtop DNA synthesis system. Evonetix believes this will break dependence on the service provider approach giving users the power to prepare gene sequences rapidly in their own laboratories.

Why enzymatic synthesis?

Evonetix first platforms will be based on thermally controlled chemical synthesis, using the thermal phosphoramidite chemistry that has been developed and refined over the last six years. According to Raquel Sanches-Kuiper, VP of Technology, enzymatic synthesis offers possibilitiesin extending the range of options for benchtop nucleic acid synthesis in the future.

“It operates under milder aqueous conditions than chemical oligonucleotide synthesis, so will ultimately be easier to deploy than chemical synthesis. It is hoped that enzymatic synthesis will eventually enable greater accuracy over long sequence lengths. Although none of the enzymatic technologies under development by different companies are yet close to achieving this we feel it is important to ensure Evonetix stays at the forefront of this developing field.”

The company has had a fruitful collaboration with with Durham University on development of modified nucleotides specifically for enzymatic synthesis. Chemists at Evonetix were familiar with Durham’s work in nucleotide chemistry and so reached out to Dr David Hodgson, Associate Professor of Chemistry at Durham and an expert in nucleotides, and established a relationship with him and his team. “The collaboration has been very successful. We won research funding from Innovate UK which has accelerated our development,” she adds.

“We are in the process of patenting our enzymatic synthesis technology based on the proof on concept we have achieved so far. We have successfully demonstrated thermally controlled enzymatic DNA synthesis – a major achievement of which the whole team is immensely proud,” says Sanches-Kuiper. The next goal is to optimise the technology. “At the moment, the enzymatic approach is still a little slower than chemical synthesis, and so the end goal is to match the performance in terms of speed and specificity,” she explains.

Looking ahead

We have a number of exciting milestones coming up,” reveals Hayes, “including preparing for our first user trial of chip synthesised DNA. In the next few months potential users will be able to apply to have us synthesise their sequences and evaluate the performance of the DNA in their own labs. They will be the first people in the world to receive DNA synthesised on our semiconductor chip and will be given access to our cloud interface to experience how users will specify their sequences as if they owned our benchtop platform. The orders will come to our lab where we will synthesise the custom sequence on chip and send it back to the user for evaluation.”

John Edgell, Head of Cloud Engineering, explains that being able to analyse and translate DNA sequences into a set of instructions for the device to synthesise and assemble can be computationally demanding. “By leveraging the power of the Cloud, we can scale our Cloud platform on demand to ensure our end-users always have enough computational power to do this quickly and accurately. As the capabilities of our platform improve and the sequences we can synthesise become longer, this will become more important.”

The work continues

“We have also received the grant of our European patent for the assembly process that we use to build gene length DNA sequences. We are continuing to miniaturise and optimise this process for our chip-based system and later this year we expect to provide a full end-to-end demonstration of how this technology performs,” says Hayes

The future

“The hope is that enzymatic synthesis will allow longer, more accurate DNA to be synthesised by benchtop platforms,” says Sanches-Kuiper. “There is huge interest in being able to synthesize long accurate DNA in your own lab. We have already seen this shift take place in DNA sequencing and I predict the same type of revolution in the synthesis market. Putting DNA synthesis in the hands of researchers, in their own lab, will open so doors to new research areas,” she adds.

Volume 23 – Issue 3, Summer 2022

About the authors

Before joining Evonetix, Dr Matthew Hayes, Chief Technology Officer, Evonetix was Head of Technology for the Global Medtech Division of Cambridge Consultants. Hayes specialises in multi-disciplinary system design, medical device development, ASIC design and opto-electronics. He holds a PhD and MEng in Electronic Engineering, both from Loughborough University. Raquel Sanches-Kuiper joined Evonetix as Director of Biology in February 2017 and became Vice President of Technology in September 2021.

Before joining Evonetix, Sanches-Kuiper was at Solexa (then Illumina Inc.) from 2002 as a Protein Engineer and major contributor to its disruptive NGS technology. Prior to that, Sanches-Kuiper was a post-doctoral researcher in the Department of Chemical Engineering and Biotechnology, University of Cambridge, in the area of cancer gene therapy. She holds a PhD in Molecular and Cell Biology from the Faculty of Medicine, University of Auvergne and a MSci in Biochemistry from the Faculty of Sciences, University of Lisbon. John Edgell, Head of Cloud Engineering, Evonetix, has been working in the software industry for over 15 years, developing cloud and mobile based application in commercial and research industries. He joined Evonetix in 2020 to lead the development of the company’s cloud platform.

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