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Key message <p><b>This review discusses the mechanisms of cross-kingdom communication mediated by small RNAs derived from Chinese herbal medicines, highlights the unique advantages of their natural delivery systems, and draws insights into the key pharmacological and biotechnological challenges for their clinical translation as novel phytosRNA therapeutics.</b></p> Abstract <p>Non-coding small RNAs (sRNAs) are increasingly recognized as pharmacologically active components in Chinese herbal medicines (CHMs), performing unique cross-kingdom gene regulatory functions. The advancement of high-throughput sequencing technology and bioinformatics has enabled the discovery and functional characterization of a growing number of CHM-derived sRNAs (CHM-sRNAs). Besides their established roles in plant growth and stress responses, these sRNAs can modulate the biosynthesis of therapeutically relevant secondary metabolites in Chinese herbal medicinal plants. These CHM-sRNAs have been shown to have great stability during gastrointestinal transit, enter systemic circulation, and participate in post-transcriptional regulation in mammalian cells. In addition, their bioactivity and stability are further enhanced by nanovesicular carriers, such as plant-derived vesicles, which provide protection against enzymatic degradation and promote cellular uptake. Despite this considerable therapeutic potential, the clinical translation of CHM-sRNAs into approved RNA drugs requires resolution of several major challenges, including the optimization of pharmacokinetic properties, establishment of adequate safety-efficacy profiles, and development of reliable administration techniques. Thus, this review systematically summarizes recent progress in the functional analysis, mechanistic understanding and pharmacological profiling of CHM-sRNAs, while critically assessing their translational potential as a new category of RNA-based therapeutic agents originating from CHMs. By integrating CHM-sRNAs into modern medicine, we provide a collaborative framework that bridges the gap between traditional Chinese medicine knowledge and contemporary molecular science.</p>

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PhytosRNA therapeutics: Cross-kingdom communication and translational potential of Chinese herbal medicine-derived small RNAs

  • 期刊论文

  • 发表日期：

    2026年6月3日

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  • Kua Hu,
  • Danyang Wang,
  • Changwei Shao,
  • Hanbing Ren,
  • Zixuan Guo,
  • Panchao Ren

摘要

Key message

This review discusses the mechanisms of cross-kingdom communication mediated by small RNAs derived from Chinese herbal medicines, highlights the unique advantages of their natural delivery systems, and draws insights into the key pharmacological and biotechnological challenges for their clinical translation as novel phytosRNA therapeutics.

Abstract

Non-coding small RNAs (sRNAs) are increasingly recognized as pharmacologically active components in Chinese herbal medicines (CHMs), performing unique cross-kingdom gene regulatory functions. The advancement of high-throughput sequencing technology and bioinformatics has enabled the discovery and functional characterization of a growing number of CHM-derived sRNAs (CHM-sRNAs). Besides their established roles in plant growth and stress responses, these sRNAs can modulate the biosynthesis of therapeutically relevant secondary metabolites in Chinese herbal medicinal plants. These CHM-sRNAs have been shown to have great stability during gastrointestinal transit, enter systemic circulation, and participate in post-transcriptional regulation in mammalian cells. In addition, their bioactivity and stability are further enhanced by nanovesicular carriers, such as plant-derived vesicles, which provide protection against enzymatic degradation and promote cellular uptake. Despite this considerable therapeutic potential, the clinical translation of CHM-sRNAs into approved RNA drugs requires resolution of several major challenges, including the optimization of pharmacokinetic properties, establishment of adequate safety-efficacy profiles, and development of reliable administration techniques. Thus, this review systematically summarizes recent progress in the functional analysis, mechanistic understanding and pharmacological profiling of CHM-sRNAs, while critically assessing their translational potential as a new category of RNA-based therapeutic agents originating from CHMs. By integrating CHM-sRNAs into modern medicine, we provide a collaborative framework that bridges the gap between traditional Chinese medicine knowledge and contemporary molecular science.