Nucleome has the unique ability to discover and validate first-in-class targets through genetics in the dark genome. Understanding the role of these genetic variants has been a long-standing challenge, hindering the translation of the human genome into useful drug discovery insights.
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 exist.
Dysregulation of this mechanism is a known cause of diseases. Indeed, 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 preponderance 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 regulate 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.