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Progress in siRNA therapy and delivery platforms for osteoarthritis
Shitang Song1,2, Wei Liu1,2, Siqi Wang3
1Sports Medicine Department, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing 100191, P.R. China.
Iscience
|April 17, 2026
Summary
Osteoarthritis (OA) treatments are advancing with small interfering RNAs (siRNAs). Engineering novel delivery systems enhances siRNA efficacy for targeting cartilage decay and inflammation, paving the way for new OA therapies.
Area of Science:
- Biomedical Engineering
- Molecular Medicine
- Rheumatology
Background:
- Osteoarthritis (OA) involves cartilage degradation, synovial inflammation, and bone remodeling.
- A cycle of matrix-degrading enzymes and pro-inflammatory cytokines drives OA progression.
- Effective OA therapies face challenges due to the complex intra-articular environment.
Purpose of the Study:
- To review current progress in small interfering RNA (siRNA) delivery systems for OA treatment.
- To explore engineering breakthroughs enhancing siRNA spatiotemporal retention and bioavailability.
- To discuss future directions for siRNA-based OA therapeutics.
Main Methods:
- Synthesis of current research on siRNA delivery architectures (viral, lipidic, polymeric, hybrid).
- Analysis of engineering strategies for improved siRNA targeting and cellular uptake.
- Exploration of advanced concepts like multi-target silencing and large animal models.
Main Results:
- Various siRNA delivery platforms show promise for intra-articular application.
- Engineering strategies significantly improve siRNA retention and bioavailability within the joint.
- Ligand-mediated targeting, surface tuning, and responsive systems enhance therapeutic potential.
Conclusions:
- siRNA delivery systems are advancing beyond experimental stages for OA.
- Engineered nanoplatforms offer a precision medicine approach to combat OA.
- Future research directions aim to translate these advancements into clinical OA treatments.
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