Nanotechnology-driven strategies for gene therapy of arthritis.

Arthritis remains a major global health burden, driven by chronic inflammation and irreversible joint damage, with current treatments often failing to achieve sustained remission. Gene therapy offers a promising strategy to address the root molecular causes by reprogramming dysregulated immune responses and promoting tissue regeneration. However, clinical translation is limited by delivery inefficiency, off-target effects, and immunogenicity. Recent advances in genetic technologies, including RNA-based therapies, DNA-based strategies, and CRISPR-Cas9 gene editing, have broadened the therapeutic toolkit for precise and durable gene modulation. Concurrently, the integration of nanotechnology has enabled the development of smart delivery platforms, such as lipid nanoparticles, polymeric carriers, inorganic nanostructures, extracellular vesicles, membrane-coated systems, and DNA nanoframeworks, to overcome biological barriers and enhance gene transfection. Moreover, emerging therapeutic strategies targeting immune modulation, synovial macrophage reprogramming, inflammatory signaling, cartilage preservation and regeneration, and pain relief further expand the clinical potential. This review provides a comprehensive overview of the key genetic tools, nanoplatforms, and therapeutic approaches driving next-generation gene therapy for arthritis, highlighting a multidisciplinary path toward precise, effective, and long-lasting treatment.