“Dark Genome” Drug Discoverer Gains $37M in Early Funds

Colorized scanning electron micrograph of a T lymphocyte. (NIAID)

19 Oct. 2022. A biotechnology enterprise discovering new drugs from non-protein coding regions of the genome is raising €37.5 million ($US 36.6 million) in venture funds. Nucleome Therapeutics Ltd. in Oxford, U.K. is a three year-old business spun-off from genetic research labs at University of Oxford medical school.

Nucleome Therapeutics is seeking new treatments for autoimmune diseases from parts of the human genome that do not give genetic instructions for cells to make proteins, the so-called dark genome. Yet these regions of the genome, says the company, still account for more than 90 percent of genetic changes responsible for disease. While not coding for proteins, says the Nucleome Therapeutics, genes in the dark genome still code for instructions to define specificity of cell types, and switching genes off and on at the right time, and with the right effect. Lack of a full understanding of the dark genome, says the company, impairs efforts to translate what we know about the human genome into new drug discoveries.

Nucleome says its technology aims to unlock the dark genome’s potential to discover new drug targets and related molecular indicators or biomarkers for designing treatments for those targets. The company says it adapts computational and experimental tools discovered in the labs of its scientific founders, geneticist Jim Hughes and genomics researcher James Davies, at University of Oxford medical school. Hughes studies genomic regulation and variations in sequences that lead to human disease states. Davies investigates new genetic sequencing methods applied to blood-forming stem cells found in bone marrow. Both Hughes and Davies use bioinformatics and other computational methods, including machine learning, in their work.

Targeting lymphocytes for new therapies

The company says its technology addressing the dark genome can pinpoint more precise genetic variations, within 256 base-pairs on average, and down to a single base-pair in some cases. A June 2021 paper in the journal Nature, led by Davies and co-authored by Hughes, describes some of these techniques.

Nucleome Therapeutics says it’s focusing on lymphocytes, white blood cells in the immune system, as targets for new therapies to treat autoimmune disorders, diseases where the immune system attacks healthy cells and tissue instead of foreign invaders. Among the more common autoimmune conditions are rheumatoid arthritis, lupus, and multiple sclerosis. Danuta Jeziorska, Nucleome’s co-founder and CEO, says in a company statement, “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.” But the company has not yet defined a specific product pipeline.

Nucleome Therapeutics is raising €37.5 million in its first venture round, funded in large part by investment arms of global pharmaceutical companies. M Ventures in Darmstadt, Germany, the corporate venture division of drug maker Merck, is leading the round. Taking part are Johnson and Johnson Innovation, Pfizer Ventures, British Patient Capital, and original investor Oxford Science Enterprises, which partners with the university to finance start-up companies based on research in its labs. According to Crunchbase, the company so far raised a total of $48.7 million.

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Disclosure: the author owns shares in Johnson & Johnson and Pfizer

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