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Discovering precision medicines to benefit patients by unleashing the power of 3D genomics

Our Mission

Shining a light on the dark genome to cure disease

The genomics era has given us deep insights into the underlying genetic causes of disease, revealing new targets for more effective drugs, and identifying the patients who will benefit from them. But there is so much more to discover, and so many cures we still need to find. With many diseases caused by multiple genetic changes, how do we understand this complexity and apply these insights to drug discovery?

The dark matter, or non-coding regions of DNA, makes up around 98% of our DNA and we now know that 90% of disease-associated genetic variations originate here. Instead of coding for proteins, this dark genome has a regulatory role: it controls gene expression. It acts like an instruction processor, turning genes on and off at the right time and levels. This enables our genetic code to be translated into the hundreds of cell types that make up the human body.

Dysregulation of this mechanism is a known cause of many diseases. Indeed, the majority of disease-linked genetic changes, including for multiple sclerosis, lupus and rheumatoid arthritis, are located within the dark genome. However, the dark genome remains largely unexplored, and the majority of these genetic changes currently have no function ascribed. The challenge in unlocking their potential to inform drug discovery is to work out which variants dysregulate which genes in which cell types and whether they exert a positive or negative impact on gene expression. Decoding this represents a significant opportunity for drug discovery and development.

Our Approach

Nucleome has the unique ability to discover and validate first-in-class targets through genetics in the dark genome.  It’s here, in the dark genome, that we find the genetic changes that impact function of regulatory switches that turn genes on and off in specific cell types – many of them located a long distance from the genes they control, making it challenging to find the connections. 

DNA is dynamically organised in three dimensions, enabling genes and their switches to connect, so gene expression occurs at the right time and in the right place. 

Genetic changes within these control switches affect gene activity, leading to disease.

At Nucleome we’re going deep into the uncharted territory of the dark genome in search of better treatments for some of the most complex diseases.

Our unique technology platform allows us to map the connections between genes and their switches with unprecedented resolution. We can then home in on how genetic changes in the dark genome affect gene activation, find which genes are involved, and explore the impact of these changes on biological pathways in specific cell types at scale.  

Our Disease Area

We are currently applying our platform technology across multiple cell types, including lymphocytes, with an initial focus on autoimmune diseases. We are focused on building a robust pipeline of drug assets with focus on biologics, with corresponding biomarkers in diseases with clear unmet need, such as systemic lupus erythematosus and rheumatoid arthritis.

Whilst the platform is agnostic to what type of drug modality is utilised; our discovery programmes are focusing on employing either monoclonal antibody or small molecule approaches.

Nucleome’s technology is also disease agnostic, and we seek to explore other disease areas through partnerships to bring a step change in pathway and target discovery.