Science
Unlocking drug targets from human genetics
Around 90% of drugs fail in clinical trials with lack of efficacy a major cause. Genetic evidence significantly improves success rates. Genome-wide association studies (GWAS) can provide genetic support in complex multi-cellular diseases (e.g. autoimmune), but interpretation is hindered by most of the associated variants being non-coding.
While statistical genetics approaches have resolved many GWAS signals, numerous loci remain unsolved or ambiguous. Functional genomics tools such as CRISPR are powerful but typically limited to cell lines or single primary cell types and require extensive time and resources. To solve human disease genetics with precision and scale, Nucleome has pioneered a platform of techniques based around understanding the root cause of how these genetic associations alter gene expression.
A different approach
We have built a de-risked pipeline through precision mapping and using purely human disease genetics and primary human cells for experimental studies. The results of Nucleome’s 3D genomics are defining a new generation of inflammatory disease targets with the potential for success beyond current industry standard.
Regulatory variants are the key to unlocking the molecular drivers of disease
Human populations harbour hundreds of thousands of naturally occurring genetic variants that are associated with disease. Most disease-associated genetic variants lie within the regulatory genome, where their effects are hard-wired into its 3D structure. These regulatory variants influence specific cell types by modulating gene expression—altering protein abundance in diseased cells—rather than through coding mutations that directly change protein structure.
Understanding the regulatory genome unlocks the mechanisms behind complex diseases, reveals which cells are at fault and shows us how to restore the immune imbalance -pointing us toward entirely new therapeutic strategies that were invisible before.
Cell-type specific expression change caused by variant in enhancer (increase or decrease)
Regulatory Genome Opportunity
Genetically informed drug discovery has primarily focused on identifying individual disease genes, revealing key drivers of disease, but offering limited insight into broader disease mechanisms. By integrating the full spectrum of genetic variants in a population, it is possible to uncover the molecular networks that define disease biology. Advancing the understanding of how regulatory genome variation contributes to disease—across all cell types and at scale—marks the next major step in genetics.