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Approved Research

Integrating large-scale genomic and phenotypic data to identify targets for gene silencing drugs and define the patient groups most likely to benefit from such drugs.

Principal Investigator: Dr Alish Palmos
Approved Research ID: 69183
Approval date: July 30th 2021

Lay summary

Scientific rationale:

The aim of those seeking to develop new medicines is precision targeting to make the treatment as effective and safe as possible for the patients to whom it is administered. Gene silencing drugs, such as those known as siRNA, treat illness by reducing the harmful effects of a gene involved in causing the illness. The effectiveness of a siRNA drug depends on selecting the best gene to silence and the patients for whom the drug is likely to offer the greatest benefit. Studies evaluating the likelihood of drugs being approved for use have shown that drugs whose target is supported by evidence from genetic analysis in humans are substantially more likely to be approved than those without such support. The UK Biobank dataset has collected genetic information about 500,000 adults along with extensive information about those individuals' health. By examining relationships between genetic and health information we will identify those genes that play important roles in a range of illnesses. Since the human genome acts as the instructions for the body's functioning in both health and disease, the genes we identify are likely to be promising targets for new siRNA treatments. Since the number of participants in UK Biobank is so large, we will be able to identify the groups of patients within all those with a given illness who are more likely to benefit from treatment with a gene silencing drug.


i. Use genetic and health information to identify promising new targets for gene silencing drugs.

ii. Evaluate the potential safety of new targets by evaluating a wide range of health information.

iii. Identify and characterise the group(s) of patients most likely to benefit from a new gene silencing drug for a given target.

Project duration:

Since the project involves ongoing hypothesis generation and testing, we propose a three-year rolling period during which we will provide annual progress updates to UK Biobank.

Public health impact:

Gene silencing drugs offer opportunities for effective and safe treatment of long-term conditions. For example, a gene silencing drug called inclisiran, approved for prevention of cardiovascular disease, has been shown to be safe and effective and is taken once every six months. By accelerating development of similarly beneficial medicines using analysis in UK Biobank, Silence Therapeutics aims to reduce the burden of long-term conditions on the health of individuals and populations, and on the health services that care for them.