Proprietary thermally-controlled synthesis chemistry will enable production of high quality DNA at scale

EVONETIX LTD (‘Evonetix’), the synthetic biology company bringing semiconductor technology to DNA synthesis, has announced it has achieved enzymatic DNA synthesis capability with its proprietary, thermally controlled synthesis chemistry. The culmination of a three-year development program, supported by Innovate UK and in collaboration with Durham University, the results demonstrate that Evonetix’s unique, semiconductor array-based platform is compatible with both chemical and enzymatic DNA synthesis, enabling the production of scarless DNA sequences that are directly compatible with downstream processing.

Synthetic biology is expected to impact many industries, but the production of high-fidelity DNA at scale, without the need for post-synthesis error correction, has remained a challenge. Evonetix‘s unique approach re-engineers traditional phosphoramidite synthesis chemistry to use thermal, rather than acidic, control of deprotection reactions. This approach enables parallel synthesis of thousands of sequences on a single chip.

The research was directed by Dr Raquel Sanches-Kuiper, VP of Technology at Evonetix, whose enzyme engineering team has focussed on the development of enzymes that can incorporate Evonetix modified nucleotides efficiently. The programme was completed in collaboration with Dr David Hodgson, Associate Professor of Chemistry at Durham University, whose group was involved in developing the modified nucleotides for enzymatic synthesis in Evonetix silicon arrays.

Dr Raquel Sanches-Kuiper, VP of Technology at Evonetix, said: “We have, for the first time, demonstrated thermally controlled enzymatic DNA synthesis. Our approach brings together thermally controlled synthesis and error detection, allowing for high-throughput assembly of high-fidelity gene-length DNA at scale. Our synthesis platform can now be used with both enzymatic and chemical synthesis, allowing us to smoothly integrate our enzymatic approach as this technology develops. Our unique, on-chip, synthesis and error correction platform will overcome many of the existing challenges in current approaches to de novo gene synthesis.”

Dr David Hodgson, Associate Professor of Chemistry at Durham University, added: “We have been able to combine our world leading expertise in nucleotide chemistry with the novel Evonetix approach for enzymatic DNA synthesis, enabling cleaner, simpler synthesis reactions that will ultimately allow for scaled production of high-quality synthetic DNA with revolutionary applications across industry and research.”

Simon Rowland, Innovate UK, commented: “Engineering Biology was identified in the 2021 UK Innovation Strategy as one of the key technologies that will deliver future economic success in the UK. The rapidly growing synthetic biology market is estimated to reach $40 billion by the mid-2020s. Innovate UK supports businesses and research institutions to drive business investment into R&D and is proud to have supported Evonetix and the development of this game changing innovation in DNA synthesis.”

About Evonetix Ltd

Evonetix is reimagining biology by developing a radically different approach to gene synthesis – a highly parallel desktop platform to synthesise DNA at unprecedented accuracy and scale. The technology builds on scalability and density from the semiconductor industry to deliver a step-change in performance for the production of DNA. The company’s platform will place DNA synthesis in the hands of every researcher and change how DNA is accessed, made and used. This new paradigm in gene synthesis will facilitate and enable the rapidly growing field of synthetic biology.

The proprietary Evonetix approach utilises a silicon chip, made by MEMS processing, that integrates physics with biology, and controls the synthesis of DNA at many thousands of independently controlled reaction sites or ‘pixels’ on the chip surface in a highly parallel fashion. The approach is compatible with both chemical and enzymatic DNA synthesis. Following synthesis, strands are assembled on-chip into double-stranded DNA in a process that identifies and removes errors, providing accuracy that is several orders of magnitude better than the conventional approach.

The Evonetix DNA writer will be a desktop device, available to every researcher, and providing scalable, accurate DNA synthesis to enable biological systems to be engineered with unprecedented accuracy and scale – this is third-generation DNA synthesis.