China the ultimate goal for digital genomic pioneers

Desktop Genetics Riley Doyle

Three Cambridge graduates pioneering digital genome editing technology are looking to break China – the world’s largest market in the arena – with what it believes is a game-changing personalised medicines proposition.

Desktop Genetics (DTG) is working with blue chip pharma companies in the US and has a distribution agreement in Japan but China is the holy grail for its growing suite of CRISPR libraries, says CEO Riley Doyle.

DTG today unveiled a new suite of six synergistic products designed to accelerate a medical revolution for biologists working with CRISPR genome editing technology.

CRISPR is a family of DNA sequences in bacteria that contains snippets of DNA from viruses that have attacked the bacterium. These snippets are used by the bacterium to detect and destroy DNA from further attacks by similar viruses. These sequences play a key role in a bacterial defence system and form the basis of a genome editing technology known as CRISPR/Cas9 that allows permanent modification of genes within organisms.

At the time of writing, DTG had raised in rapid time £781k – 52 per cent of a £1.5 million target – on Cambridge equity crowdfunding platform SyndicateRoom. Cambridge serial entrepreneur and DTG investor Jonathan Milner is lead backer.

Doyle told Business Weekly that the £1.5m would take DTG to profitability by 2019. Rather than grabbing at every new shiny but unproven opportunity that might present itself on its journey, DTG would focus on building a viable, robust and sustainable business first and foremost.

“What happens further down the road – IPO or sale of the company – is not up to me. Companies aren’t sold – they are bought. Shiny entrepreneurial opportunities can pop up at any time but we have to remain focused and commercial and develop a company built to last.”

DTG’s current push for international expansion is predicated on the swift progress of CRISPR technology which has gone from proof of concept in around 2014-15 to a demonstrable commercial breakthrough.

Doyle believes it provides the roadmap to genuinely personalised medicines where different drugs can be tailored to the individual make-up of every patient on the planet.

DTG’s new series consists of six new base CRISPR library products which can be tailored to an investigator’s list of genomic targets using any delivery method. Each product addresses a particular experimental application of the genome editing technology. The Disrupt Libraries offering can be used to functionally knock out genes to reveal novel druggable targets and essential pathways.

DTG’s Tile Libraries saturate coding and non-coding regions to reveal genotype-phenotype relationships.

SNP-In Libraries allow high-throughput insertion and deletion knockins across the genome; Interfere Libraries silence target gene expression with CRISPRi while  Activate Libraries allow over-expression of target genes with CRISPRa.

Finally, DTG’s Predict Libraries provide a unique scoring algorithm optimised for teams working on specific model cell lines or organisms, enabling other libraries to be designed more effectively.

Once DTG receives a customer’s list of targets along with their experimental intent, the company designs the library using its proprietary DESKGEN AI and suite of bioinformatics pipelines. 

The validated technology employs machine learning techniques combined with the largest database of experimental CRISPR outcomes in the industry to select the guides most appropriate for the chosen targets and experiment. Once the designs are complete, the company manufactures the library in a variety of ready-to-use formats. 

Doyle says that, unlike off-the-shelf CRISPR libraries, DESKGEN Libraries allow researchers to look at the targets they’re interested in, opening the door to novel discovery. 

By meeting the client’s requirements with a bespoke CRISPR library, designed with the latest know-how in genome editing, these new products provide researchers with fewer false positives and negatives and the confidence needed to support claims made in basic and preclinical research. The company supports both large and small-scale library development and can meet the needs of both functional genomics and drug discovery laboratories regardless of budget.

Doyle said: “This is the first time that such best-in-class CRISPR libraries have been made available in a fully customisable manner and, as such, researchers neither have to waste time designing libraries themselves, nor take a risk that the data generated from an off-the-shelf alternative will yield redundant, obsolete or incorrect data that might jeopardise or stall follow-up research programs. 

“As we’re committed to maintaining the supremacy of the DESKGEN AI design platform, we will continue to deliver more and more solutions that enable novel discovery in all fields using CRISPR, whether it’s drug discovery, agricultural biotech, or fundamental research.” 

Doyle says DTG has achieved high growth since startup in 2012 to target a genome engineering market estimated to be worth around $2.84 billion globally and set to grow to more than $6bn by 2021. By that time it is estimated that between 60,000 and 100,000 labs will be using CRISPR technology.

“Despite this, over half of all new medicines in development today are likely to never reach patients – often because they are based on flawed science,” says Doyle. He believes CRISPR will do for drug development and delivery what AI is promising today across a raft of high technology segments.

Anchored off Brick Lane in London’s entrepreneurial heartland of Shoreditch, DTG also has a commercial headquarters in Boston, Massachusetts – a city which represents the heart and lungs of the CRISPR ecosystem – and Doyle says the bulk of business is currently being generated with US customers.

As well as collaborating with Big Pharma corporates, DTG also works with leading academic institutions, hospital research and general medical research organisations globally.

Doyle says: “While the bulk of our customers are in the US we have a distribution agreement in Japan and we can do a lot more business in the European market. There is huge untapped potential in China, the world’s biggest market for our technology, with the government there committed to investing large amounts of money in new healthcare solutions.

“Regulatory wise it is also arguably the most difficult market to negotiate successfully but it is very much on our radar and is well worth the effort.”

Doyle revealed that DTG had recently been on the cusp of a $7m round to fund expansion on a much grander scale in terms of tech and territories; even that was modest compared to recent deals by major players in the sector that have topped as much as $76m.

For a variety of reasons the $7m investment didn’t make it over the line and DTG decided on a more modest short-to-medium term strategy with the crowdfunding raise driving it to profitability. 

The need to raise additional growth capital is under constant review but, as Doyle observes: “The cool thing about us is that we are a virtual biotech and the £1.5m crowdfunding cash will go towards our commercial growth rather than being spent on a large rent at a Cambridge science park.

“Our business model makes us more agile and we are utterly committed to being extremely efficient in everything we do.”

Being a digital biotech also enables DTG to operate a discerning employment strategy, hiring the best talent rather than going for volume; for example, it has had several interns working with management over the summer as part of a full team of just 16 including the three co-founders who are the senior executives. DTG hires interns on a rolling basis and recruits from around the world.

Doyle explains: “The interns have the best ideas. They come in with so much energy and enthusiasm and inspire the whole team.”

Heads may change but the core strategy for future scale-up remains rooted in pragmatism. DTG will not be seduced into chasing scattergun opportunities – what Doyle calls the ‘flavour of the week phenomenon.’ “We are concentrating on technology that solves a real problem.”

One edge that DTG enjoys is that it is dealing in the here and now. It is unencumbered by historic attempts to target a certain disease with an experimental drug that may have started development 15 years ago when circumstances were different and knowledge comparatively limited.
Such legacy plays can flop on day three when they finally reach clinical trials and are rendered past their relevance as diseases and lifestyle choices have moved on.

As Doyle observes, everyone on the planet has a different genetic make-up and only by gathering as much genetic data on as many people in the world as possible will drug delivery provide effective cures for individuals with specific problems.


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