This research leverages UK Biobank’s extensive genomic, phenotypic, and health data to identify and prioritize therapeutic targets for multiple diseases, assess their safety, and explore opportunities for RNA-based drug development.
Research Questions:
1. Which genes, when modulated, can provide therapeutic benefit to individuals with specific diseases?
2. Are candidate targets safe to modulate based on genetic and phenotypic data?
3. How can phenotypic and genetic data be integrated to identify biomarkers for disease progression, and help with patient stratification?
Objectives:
1. Target Identification and Prioritization: pinpoint new target genes and pathways that are implicated in disease development and progression.
2. Genetic Associations: Investigate genetic associations to establish robust links between candidate targets and diseases.
3. Safety Assessment: Analyze natural genetic variations to evaluate the safety profiles of candidate targets.
4. Mechanistic Insights: Uncover biological mechanisms linking targets to diseases to enhance understanding of pathophysiology.
5. Biomarker Discovery: Identify biomarkers for disease progression, response, and patient stratification.
Scientific Rationale:
RNA therapeutics offer precise gene modulation and transformative options for diseases with unmet needs, but drug development often fails due to efficacy or safety concerns. Genetically supported targets are more likely to succeed in clinical development.
The UK Biobank offers a unique resource to link genetic variation with disease outcomes, uncovering therapeutic targets underpinned by strong genetic evidence. This approach not only validates target relevance but also assesses safety through natural loss-of-function variants and identifies biomarkers to support personalized medicine.
By leveraging these data, RNA-based drug discovery can be accelerated, improving success rates and advancing therapeutic innovation.