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Innovative 'gene-silencing' therapy to target chronic pain in osteoarthritis

A new peptide-siRNA drug delivery system could revolutionise treatment for osteoarthritis by targeting pain and inflammation at the source.

3 June 2025•2 min read
Close-up of elderly man holding his knee in pain whilst he's sitting on a sofa.

A new University of Birmingham-led study could pave the way for a targeted treatment for osteoarthritis (OA) that directly tackles inflammation and chronic pain in the joint — without the side effects often associated with current therapies.

Funded by Versus Arthritis and beginning in September 2025, the three-year project led by Professor Simon Jones will develop and test a new class of drug molecules known as peptide-siRNA conjugates. These novel compounds are designed to silence disease-causing genes within the joint lining and cartilage, using short strands of genetic material (siRNAs) delivered precisely to the cells driving pain and inflammation.

Osteoarthritis affects over 500 million people worldwide and is a leading cause of disability. Current treatments mainly focus on symptom management, often with limited effectiveness and undesirable side effects, leaving many patients to struggle with chronic pain and, eventually, joint replacement surgery.

In a recent survey, the research team found that 86% of OA patients reported that existing treatments provide limited pain relief, and 46% experience significant side effects. OA pain significantly impacts daily activities, with 60% of patients reporting difficulties in performing physical tasks such as walking or running. The potential benefits of a new treatment for OA patients are therefore substantial.

siRNAs represent a promising new class of drug, offering advantages over traditional drug classes.

Professor Simon Jones, Principal Investigator, Professor in Musculoskeletal Ageing, University of Birmingham

Principal Investigator of the study, Professor Simon Jones, explains: "siRNAs represent a promising new class of drug, offering advantages over traditional drug classes. However, effective targeted delivery of siRNAs into the disease relevant cells is a challenge." 

"If successful, our approach will provide a gateway platform for the development of peptide-siRNAs conjugates against other targets in patients across the spectrum of musculoskeletal ageing and arthritic diseases including rheumatoid arthritis, psoriatic arthritis and axial spondylarthritis."

The research builds on recent findings by the team that a specific group of cells in the joint lining — synovial fibroblasts — play a major role in OA-related inflammation, particularly in people with obesity. These cells produce inflammatory substances that contribute to joint damage and persistent pain.

The new therapy will use small interfering RNAs (siRNAs) to silence genes known to trigger inflammation in OA. To overcome the challenge of delivering siRNAs directly into joint cells, researchers will attach them to peptides — short chains of amino acids - that act as targeting agents. These peptides will home in on a specific type of receptor, found in high numbers on inflamed joint cells, ensuring the treatment is delivered precisely where it is needed and limiting potential side effects.

This approach aims to bypass common problems with systemic drug delivery, which can result in side effects such as cardiovascular complications. Non-steroidal anti-inflammatory drugs (NSAIDs), currently the most widely used OA treatments, are only effective short-term and are not suitable for long-term use by many patients.

The new peptide-siRNA conjugates will first be tested in OA patient tissue samples to assess their impact on pain and inflammation markers. The most promising candidates will then be trialled in animal models of arthritis.

Dr Caroline Aylott, Head of Research Delivery at Versus Arthritis, said: "Millions of people with osteoarthritis are living every day with debilitating pain and limited treatment options. This pioneering project is part of our Early Detection and Targeted Treatments priority funding call and reflects our commitment to backing bold, innovative science that has the potential to help us identify the signs of arthritis earlier and develop effective drug and non-drug targets to reduce the impact of arthritis. By targeting the root causes of pain and inflammation at the cellular level, this research could open the door to a new generation of precision medicines for osteoarthritis and beyond."

If successful, the study could offer long-lasting relief for OA patients while potentially slowing disease progression — a significant advance given the lack of approved disease-modifying treatments for osteoarthritis. The researchers also hope the platform could be extended to develop similar treatments for other inflammatory joint conditions.

The research is a collaboration between the University of Birmingham, the Versus Arthritis Pain Centre at the University of Nottingham, and the University of Bath.

Notes for editors

About the University of Birmingham

  • The University of Birmingham is ranked amongst the world’s top 100 institutions. Its work brings people from across the world to Birmingham, including researchers, educators and more than 40,000 students from over 150 countries.
  • England’s first civic university, the University of Birmingham is proud to be rooted in of one of the most dynamic and diverse cities in the country. A member of the Russell Group and a founding member of the Universitas 21 global network of research universities, the University of Birmingham has been changing the way the world works for more than a century.

About Versus Arthritis

Versus Arthritis is the largest arthritis charity and the biggest dedicated charitable investor of arthritis research in the UK, changing lives through research, campaigning and support.     

The impact of arthritis can be huge, affecting the ability to learn, work, care for family, move free from pain and live independently. Together with researchers, healthcare professionals, policymakers, supporters and volunteers, Versus Arthritis works tirelessly to make sure everyone with arthritis has access to the treatments and support they need to live the life they choose, with real hope of a cure in the future.      

Find out more at: www.versusarthritis.org | Twitter/X | Instagram | Facebook | LinkedIn  

Featured staff

  • Professor Simon W Jones

    Professor in Musculoskeletal Ageing

    Staff profile for Professor Simon Jones, Professor in Musculoskeletal Ageing, Department of Inflammation and Ageing, College of Medicine and Health, The University of Birmingham.

    Phone: +44 (0)121 371 3224
    Email:

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