Annual development trends in technological innovations and therapeutic applications of RNA therapy

Driven by synergistic breakthroughs in chemical modifications, delivery technologies, and mechanistic understanding, RNA therapeutics—spearheaded by oligonucleotide therapeutics and mRNA technologies—has rapidly evolved from fundamental discoveries into a phase of extensive clinical translation. It now stands as a pivotal frontier in global biomedical innovation. This review systematically analyzes the progress in 2025 across foundational platforms, disease-targeting research, clinical development, and industrialization, while assessing future trends and offering strategic recommendations. At the technology level, sequence and structural design have become more refined, evolving from an empirical and rule-dependent approach to a new stage of AI-driven rational design. Advances in chemical modification technologies targeting the backbone, ribose, and nucleobases continue to enhance RNA stability and effectively reduce immunogenicity, while achieving precise and intelligent modulation has emerged as a focal point in the field. Although current delivery systems remain dominated by liver-targeting approaches using lipid nanoparticles (LNPs) and GalNAc conjugates, next-generation technologies are diversifying toward overcoming hepatic clearance and achieving tissue-specific targeting. Meanwhile, the application of artificial intelligence tools is significantly accelerating the processes of sequence design and delivery vehicle screening. In the field of basic and clinical research, the application of oligonucleotide therapeutics is rapidly expanding from genetic disorders to chronic diseases such as cardiovascular and neurodegenerative conditions. mRNA technology has also advanced beyond infectious diseases into oncology and metabolic disorders, with particularly deepening progress in cancer immunotherapy, where personalized neoantigen vaccines have achieved milestone developments. Capitalizing on its inherent stability, circular RNA (circRNA) has emerged as a highly promising platform for novel vaccines and therapeutic drugs. As these technologies mature, the industry is transitioning from the proof-of-concept phase to commercial-scale production. Supported by innovative platform technologies and global collaborations, China is rising as a pivotal force in global biomedical innovation. Looking ahead, critical challenges remain in achieving extrahepatic tissue-specific delivery, realizing precise and tunable regulation, and understanding long-term biological effects. Overcoming these hurdles is essential for developing the next generation of accurate, safe, and broadly applicable RNA therapies.