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U.K. startup Nucleome Therapeutics Limited has raised £37.5 million in an oversubscribed Series A funding round to further its explorations into how dark matter in the human genome can be decoded to deliver precision medicines.

The University of Oxford spinout has attracted the interest of Big Pharma, with the latest investors including the venture capital arms of Merck KGaA, Johnson & Johnson and Pfizer.

Also contributing were founding investor Oxford Science Enterprises and British Patient Capital, a wholly owned commercial subsidiary of the U.K. government’s economic development bank.

Nucleome combines 3D genome technology with machine learning to cast light on biological dark matter, which makes up over 98 percent of the human genome.

This non-coding RNA does not provide the blueprint to build proteins. Rather, it acts as an instruction booklet that switches genes off and on at particular times to varying degrees and allows the single genetic code to be translated into different cell types.

Dark matter contains 90 per cent of disease-linked genetic changes, but most have no function currently ascribed to them and shedding light on them could provide important avenues for drug discovery.

Currently, the company is using its technology across multiple cell types, including lymphocytes, with an initial focus on autoimmune diseases. It is also aiming to develop a drug pipeline, with biomarkers, for diseases with unmet needs such as systemic lupus erythematosus and rheumatoid arthritis.

“We have already made significant progress by mapping genes to genetics in a number of human immune cell types and discovering the first wave of potential first-in-class autoimmune disease targets,” said Danuta Jeziorska, PhD, Nucleome Therapeutics CEO and co-founder in a press statement. 

Bauke Anninga, principal at Merck KGaA’s strategic, corporate venture capital arm M Ventures, added: “Nucleome’s differentiated platform technology has the potential to fundamentally shift the way we discover and develop precision medicines. Unlocking the value of the largely unexplored territory of the genome can lead to the identification of high-value drug targets.”

Nucleome’s pioneering platform combines state-of-the-art computational and experimental approaches.

A machine learning model predicts disease-associated genetic variants that create and destroy functional elements in the dark genome and can also be used to identify cell types affected by these.

The company’s 3D genome analysis methods experimentally link the variants to genes and functional validation technology defines their impact on different cell types.

Assays done at scale allow disease-affected pathways to be mapped and determine how cell types are regulated both when healthy and in disease.

The company has undergone a spate of recruitment this year, establishing an advisory board, appointing a chief financial officer and chief business officer and, most recently, a vice president of operations.

But there are others competing in the field and interest looks likely to grow with the first, gap-free human genome sequence published earlier this year in the journal Science.

U.S. competitors Omega Therapeutics and CAMP4, both based in Cambridge, Massachusetts, have each recently completed successful funding rounds.

Meanwhile, in academia the Dark Matter Project, based at the Center for Synthetic Regulatory Genomics at NYU Langone Health, aims to systematically elucidate the mechanisms of regulatory variation in disease.

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