The Mechanistic Review of the Molecular Interface of RNA-Loaded Extracellular Vesicles: Redefining Targeted Therapy for Autoimmune Disorders

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Traditional treatments of autoimmune diseases relying on systemic immunosuppression often lack curative potential and have severe side effects. Mesenchymal stem cells (MSCs) are a promising alternative due to their immunomodulatory properties; however, whole-cell therapies have certain limitations. MSC-derived extracellular vesicles (EVs), including small vesicles-exosomes-have emerged as a safe cell-free therapeutic platform capable of crossing biological barriers and delivering bioactive cargo with low immunogenicity. Various types of RNAs abundantly produced by host MSCs represent a key element of EV content. In particular, EVs carry small RNAs, which essentially determine cellular life and fate. Our review provides a comprehensive mechanistic framework for the use of RNA-loaded EVs, specifically those carrying microRNAs (miRNAs), small interfering RNAs (siRNAs), and messenger RNAs (mRNAs), in restoring immune homeostasis. We detail the biogenesis and molecular mechanisms governing sorting of RNA into EVs, along with endogenous and exogenous engineering strategies to enhance therapeutic potency. We examine how RNA-loaded EVs modulate immunological processes like reprogramming of macrophage M1-M2 polarization, Th17/Treg balance, and suppression of inflammatory signaling pathways such as NF-κB and the NLRP3 inflammasome. We address critical translational challenges-EV heteroge

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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