Oligonucleotide therapeutics have emerged as powerful modalities for precise gene regulation. To accelerate the discovery of safe and effective targets, OliX will utilise the UK Biobank’s extensive genomic and phenotypic data to identify genes and pathways whose modulation at the RNA level may prevent or treat human disease. By integrating genetic variation with clinical and biomarker data, we aim to uncover causal relationships between genotypes, biological pathways, and disease outcomes.
This research will focus on discovering and validating therapeutic targets across the liver, central nervous system (CNS), and adipose tissues. While the liver is the most established organ for siRNA delivery, growing evidence highlights the therapeutic potential of extrahepatic tissues. Through genome-wide association studies, fine-mapping, and integration with expression quantitative trait locus (eQTL) resources, we will link genetic variants to gene-level functional effects and disease phenotypes-identifying targets whose regulatory direction aligns with siRNA-mediated suppression.
Broad phenome-wide association analyses (PheWAS) across the UK Biobank’s rich phenotype data will be used to predict potential safety liabilities and pleiotropic effects of target modulation. These analyses will inform early risk assessment and guide safer drug development strategies. By further integrating genotype-phenotype associations with clinical traits and biomarker profiles, we will identify subgroups of individuals most likely to benefit from target modulation. This patient stratification framework will enhance precision in indication selection and future clinical trial design.
Through this integrative, approach, OliX aims to establish a robust framework for target prioritisation, safety prediction, and precision drug development. The project aligns with the UK Biobank’s mission to translate human genetic insights into therapeutic innovation and supports.
