Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, for which gene therapy provides a potential therapeutic strategy. Among various approaches, RNA interference (RNAi) technology has garnered considerable attention. This review summarizes the research progress of RNAi technology for ALS, including the pathogenic genes, effector molecules, and the application of vector delivery systems. Meanwhile, we note that current research has predominantly focused on the superoxide dismutase 1 (SOD1) gene, while studies on RNAi strategies targeting other core ALS-causing genes remain relatively scarce. Furthermore, technical challenges persist, including immunogenicity and off-target effects, etc. This review concludes that optimizing the specificity of RNAi molecules and delivery systems, expanding targeted genes, and balancing potency with safety are the core directions for future research.

Inflammatory Bowel Disease (IBD), comprising Crohn’s disease (CD) and ulcerative colitis (UC), is a group of chronic relapsing inflammatory disorders of the gastrointestinal tract with complex etiology and significant clinical challenges. Extracellular vesicles (EVs) act as key mediators of intercellular communication, carrying diverse RNA species—especially non-coding RNAs such as microRNAs and long non-coding RNAs—which have emerged as critical regulators in IBD pathogenesis and progression. This review synthesizes current understanding of how EV-associated RNAs modulate fundamental IBD-related processes, including inflammatory signaling, intestinal barrier function, immune regulation, and host–microbiota interactions. By integrating recent evidence from multi-omics studies and animal models, we highlight the promise of EV-derived RNAs as novel biomarkers and therapeutic targets. We further discuss advances in EV-RNA-based therapeutics and examine the challenges and future directions for translating these insights into clinical practice. By elucidating the multifaceted roles of EV-RNAs in IBD, this article aims to provide a theoretical foundation and inform future research toward precision diagnosis and personalized treatment strategies for IBD patients.

Recent years have brought the groundbreaking discovery of trained innate immunity, characterized by enhanced monocyte, macrophage and NK cell microbicidal activity. A functional shift of the involved cells results from metabolic rewiring and epigenetic modifications that, among others, are driven by long non-coding ribonucleic acid (lncRNA)-induced effects. However, many questions remain unanswered regarding the precise molecular pathways that ensure trained immunity. In this Commentary article, we aimed to present a comprehensive summary of the key findings from a recently published study that identified a role for lncRNA in monocyte training in the context of tuberculosis. Interestingly, this extracellular vesicle-transferred lncRNA has been shown to stabilize clock circadian regulator (CLOCK) mRNA and, in turn, augment its translation. Consequently, CLOCK-induced histone acetylation upregulates the expression of immune and circadian genes in trained monocyte-derived macrophages. These lncRNA-induced effects were demonstrated to increase antimicrobial resistance after immunization with the Bacillus Calmette-Guérin (BCG) vaccine as well as during unrelated infections. These latter features are desirable characteristics of trained immunity.