MicroRNA-146a Modulation by Targeted Lipid Nanoparticles to Treat Rheumatoid Arthritis: A Proof-of-Concept RCT
DOI:
https://doi.org/10.61919/h1fggw78Keywords:
Arthritis, Rheumatoid; C-Reactive Protein; Drug Delivery Systems; Epigenomics; Lipid Nanoparticles; MicroRNA-146a; Nanomedicine; Randomized Controlled Trial; RNA Therapeutics; Targeted Therapy.Abstract
Background: Rheumatoid arthritis is characterized by persistent synovial inflammation and dysregulated immune signalling. MicroRNA-146a negatively regulates innate inflammatory pathways, but its therapeutic application requires an effective intracellular delivery system. Objective: To evaluate the preliminary clinical efficacy and safety of microRNA-146a encapsulated within folate-receptor-targeted lipid nanoparticles in adults with active rheumatoid arthritis. Methods: This single-centre, double-blind, randomized controlled trial enrolled 80 adults receiving stable conventional synthetic disease-modifying antirheumatic therapy. Participants were allocated 1:1 to weekly intravenous microRNA-146a lipid nanoparticles at 0.1 mg/kg or matching empty vehicle nanoparticles for six weeks. The primary outcome was change in DAS28-CRP. Week-6 effectiveness analyses included 74 completers, and safety analyses included all 80 treated participants. Results: DAS28-CRP decreased from 5.45 ± 0.71 to 3.12 ± 0.54 in the intervention group and from 5.39 ± 0.65 to 4.98 ± 0.61 in the control group. The week-6 between-group difference was −1.86 points (95% CI: −2.13 to −1.59; p < 0.001). Week-6 between-group differences also favoured the intervention for CRP (−13.9 mg/L), ESR (−17.7 mm/hour), and VAS pain (−27.9 mm; all p < 0.001). Three minor adverse events occurred in the intervention group; no serious adverse events were recorded. Conclusion: Targeted microRNA-146a delivery was associated with greater short-term reductions in disease activity, inflammation, and pain than vehicle nanoparticles. Larger, longer-duration studies are required to confirm efficacy and safety
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Copyright (c) 2026 Muhammad Abbas Sadiq, Samira Khaliq, Muhammad Laiq, Zuheeb Ahmed, Zoya Zafar, Hajrah Iftikhar, Muhammad Hussain, Muhammad Shahzaib (Author)
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