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Vishal Gulati

Genomics 👉 SynBio: Welcome Evonetix

January 31, 2018

The genomic century has only just started. Get your seatbelts on!

Today, we are delighted to announce that Draper Esprit and DCVC are leading a $12.3m investment in Cambridge UK based company, Evonetix . I will be joining the board along with Matt Ocko, co founder of DCVC, and a leading voice in Silicon Valley deep tech VC community.

Evonetix is making a DNA chip to accurately synthesise long pieces of DNA and fits with Draper Estprit’s investment thesis to back the most promising companies downstream of DNA sequencing (previously, we invested in Horizon Discovery which does CRiSPR gene editing and Fluidic Analytics which does protein characterisation — both also based in Cambridge).

DNA is in UK’s DNA:

Most people know that UK has had a pretty successful run when it comes to DNA related technologies.

1953: at a pub called The Eagle Watson announced that he and his colleagues had discovered the secret of life. He was building upon the work of Rosalind Franklin in 1952 (Watson, Krick, Wilkins get Nobel Prize, Franklin did not).

1977: Fred Sanger inventing method to sequence DNA (Sanger Method). Gets Nobel Prize

1992- 2001: Wellcome Trust became the biggest non-US funder and Sanger Centre, the biggest non-US site) of the Human Genome Project

1997: Balasubramanian and Klenerman invented yet another method of sequencing DNA (rumour has it that the idea was conceived at Panton’s Arms)— only a zillion times faster than Sanger Method — started Solexa. This is the most widely used method of DNA sequencing. (It powers Illumina’s DNA sequencing machines)

2006: UK Biobank, the world’s first large scale, long-term biobank study in the which is investigating the respective contributions of genetic vs environmental exposure (including nutrition, lifestyle, medications etc.) to the development of disease.

2012: The 100,000 Genomes Project started sequencing whole genomes from NHS patients. The project is focusing on rare diseases, some common types of cancer, and infectious diseases

2015: Herman Hauser inspired former members of Solexa team to come together to build the new Evonetix chip — to do to writing DNA what Solexa did to reading DNA.

Evonetix Chip is Solving a Fundamental Bottleneck:

The ability to synthesise fragments of DNA without the limitation of sequences and with no errors is a fundamental challenge in the way of developing the next generation of DNA-based products. All existing DNA manufacturing methods only produce short sequences because longer sequences have higher rates of errors.

Prototype of Evonetix Chip (magnified) ©Evonetix Limited

Not being able to have control over this process limits our ability to write freely. It locks us out of some of the most powerful applications of genetic technologies. Evonetix might hold the key for unlocking the true power of synthetic biology as envisioned by say, Juan Enriquez in As The Future Catches You in 2001.

If we printed books like we make DNA today we would be telling J K Rowling that she is welcome to write Philosopher’s Stone, as long as she doesn’t use too many Gs and Cs and kept her sentences to a maximum of 4 words.

DNA is made of four chemicals (nucleotide bases A,T,C and G) and the orderin which they are connected carries the message to the cellular machine. Any change in order in a coding region can at best stop it functioning, and at worst be devastating, just like a tiny spelling error in the code of your software can crash your computer or take your website down. In humans, we see this in case of sickle cell anaemia which is caused by a known mutation of a single nucleotide (A ➤ T) of the β-globin gene making a weird form of haemoglobin which becomes spiky when oxygen levels drop. Or cystic fibrosis, which in most cases is caused by three missing letters in the CFTR gene.

Synthetic Biology (SynBio):

SynBio is the emerging set of technologies which allow us to make things using biological systems as a manufacturing platform. Over the last few years several billions of dollars have been invested into this emerging field to back promising companies like Gingko Bioworks ($429m). The sector has started to emerge in the UK eg Synthase ($16m), LabGenius ($4m).

Almost all SynBio journeys start with biological code, DNA. The industry needs large quantities of custom DNA sequences, a process which is currently a bottleneck.

Rising Annual Investment in Synthetic Biology Companies Globally

Making DNA Is Hard. Making Good DNA is Very Hard

The ideal process of making DNA would be fast, cheap and accurate. Current methods are anything but. They fail to make long sequences of DNA that are accurate.

Processes currently used to make DNA (inkjet printing, biological/enzymatic synthesis) have a mechanistic error rate i.e. as the length of DNA grows, the probability of error grows so it is almost impossible to make accurate DNA sequences beyond a certain length. So much so that today it is not possible to recreate the sequences of genes that encode for some of the most important drug targets and enzymes. However, length is not the only limitation of current methods because certain types of sequences (“GC rich”) are also hard to make.

Evonetix Chip Controller ©Evonetix Limited

Evonetix is led by Tim Brears as CEO (formerly Novartis, Gendaq and Xention). His team includes some key people from the old Solexa team (including Nick McCook on the board) and a solid engineering team out of Cambridge Consultants.

The best scientific breakthroughs happens when we bring experts in different scientific disciplines together to address a big problem. That is what happened at Solexa (computing + chemistry + optics). As we speak, engineers, biologists, chemists are working to build the Evonetix chip which, when ready, would make unrestricted lengths of accurate DNA to make the next generation of drugs, enzymes, proteins and things we don’t even know we need, or that we can now make and eventually won’t be able to live without.