Advancements in Plant-Derived sRNAs Therapeutics: Classification, Delivery Strategies, and Therapeutic Applications.

Plant-derived small RNAs (sRNAs) have garnered significant attention in nucleic acid therapeutics, driven by their distinctive cross-kingdom regulatory capabilities and extensive therapeutic promise. These sRNAs exhibit a wide range of pharmacological effects, including pulmonary protection, antiviral, anti-inflammatory, and antitumor activities, underscoring their substantial potential for clinical translation. A key advantage lies in their delivery, facilitated by plant-specific nanovesicular carriers-such as plant exosomes, herbal decoctosomes, and bencaosomes-which protect sRNAs from gastrointestinal degradation and enable precise, tissue-specific targeting. This review provides a comprehensive analysis of plant-derived sRNAs, detailing their classification, gene-silencing mechanisms, and nanovesicle-mediated cross-kingdom delivery strategies. It further explores their therapeutic potential and underlying molecular mechanisms in major human diseases. Additionally, we critically evaluate current technical challenges and propose future directions to advance the development of plant-derived sRNAs for precision therapeutics. This work aims to offer a robust theoretical framework and practical guidance for the clinical advancement of plant-derived sRNA-based therapies.