Aug 2026· Small· pp.
e75396
· 0 citations· 44 references
Medicine
TL;DR
The unique properties of saRNA have positioned it as an innovative tool for the treatment of various diseases, unlocking more possibilities for clinical applications and outlining future directions for the field.
Abstract
mRNA therapeutics have garnered significant attention in recent years due to their remarkable success in addressing unmet medical needs across diverse fields, including infectious diseases, cancer, and hereditary disorders. Among the various modalities of mRNA therapeutics, self-amplifying mRNA (saRNA) has emerged as a particularly promising platform. Distinguished by its ability to achieve robust protein expression at lower doses, saRNA offers several advantages, including higher cumulative expression levels and significantly extended expression durations. But the questions of how and where saRNA technology will evolve in the coming years remain underexplored. In this review, we provide a comprehensive overview of saRNA therapeutics, beginning with a detailed explanation of their underlying mechanism of action. We then systematically summarize the preclinical and clinical advancements in saRNA-based therapies, highlighting their applications across a broad spectrum of diseases. We then discuss the key challenges currently faced by saRNA therapeutics and propose potential strategies to overcome these barriers. Finally, we outline future directions for the field, emphasizing the transformative potential of saRNA in clinical applications. In summary, the unique properties of saRNA have positioned it as an innovative tool for the treatment of various diseases, unlocking more possibilities for clinical applications.
This review first provides a concise overview of the mechanistic principles underlying oligonucleotide function and commonly employed chemical modification techniques, and highlights recent advancements in receptor-mediated delivery systems for extrahepatic targeting, and dual-targeting oligonucleotide engagement strategies.
Liuhai Chen, Jiahao Xu, Jin Li et al.· The Innovation Drug Discover...· 2 citations
It is suggested that the effectiveness of mRNA cancer vaccines depends not only on selecting the right antigens but also on delivery methods that modulate the immune response and reshape the tumor microenvironment.
Dianzhe Tian, Xin-Shi Li, Zuyi Yang et al.· Frontiers in Pharmacology· 0 citations
This comprehensive review examines the molecular architecture and mechanisms of established platforms in the clinical setting, including mRNA, antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs) and aptamers, alongside next-generation platforms, such as CRISPR-guided systems and circular RNAs (circRNAs).
Konstantina Athanasopoulou, Glykeria N. Daneva, V. Michalopoulou et al.· Current Issues in Molecular...· 0 citations
Messenger RNA (mRNA)-based vaccines, including circular RNA (circRNA) and self-amplifying RNA (saRNA), have emerged as the most transformative platforms, offering tremendous potential in prophylactic and therapeutic medicine, particularly in the prevention of infectious diseases and cancer immunotherapy. Nevertheless, their optimization remains limited by the instability of mRNA, its innate immunogenicity, and low protein expression efficiency in vivo. In recent years, rapid advancements in mRNA sequence design and delivery technologies have improved therapeutic protein production and enhanced vaccine efficacy and safety. This article reviews mRNA-based vaccines, including conventional non-replicating mRNA and emerging approaches such as circRNA and saRNA, with a focus on recent progress, sequence optimization, and delivery systems. Additionally, the article highlights recent advancements in computational technologies for vaccine design. Finally, the article outlines current manufacturing challenges and potential solutions.
Zijia Guo, Jiayan Fu, Luna Ran et al.· Molecular Therapy· 0 citations
Simple Summary Cancer treatment has improved substantially over recent decades, yet many patients eventually develop resistance to therapy, limiting long-term treatment success. Increasing evidence suggests that long non-coding RNAs (lncRNAs), a class of RNA molecules that do not produce proteins, play important roles in helping cancer cells survive treatment and adapt to therapeutic pressure. These discoveries have generated interest in lncRNAs as potential therapeutic targets. At the same time, recent advances in RNA medicine have demonstrated that disease-causing RNA molecules can be successfully targeted in patients. In this review, we discuss the emerging role of lncRNAs in cancer therapy resistance and examine how advances in RNA-based treatments may create new opportunities to overcome this challenge. We also highlight key obstacles that must be addressed before lncRNA-targeted therapies can be translated into clinical practice. Improved understanding of these mechanisms may ultimately contribute to more effective and durable cancer treatments.
Messenger RNA (mRNA) technology has emerged as a cornerstone in vaccine development and therapeutic applications, offering key benefits such as high potency, rapid scalability, and cost-effectiveness. The success of COVID-19 mRNA vaccines has underscored their efficacy and safety. However, residual byproducts generated during mRNA synthesis, such as unincorporated caps, nucleoside triphosphates (NTPs), DNA templates, enzymes, abortive transcripts, and double-stranded RNA (dsRNA), pose significant challenges to the clinical application of the RNA therapy. Among these, dsRNA is particularly problematic as it can activate various innate immune responses, suppress mRNA translation and potentially compromise the therapeutic efficacy of mRNA. Therefore, effectively removing dsRNA from in vitro synthesized mRNA is essential before its used in preclinical or clinical settings. In this review article, we provide a comprehensive overview of current mRNA development pipelines and ongoing clinical trials, and recent advances in mRNA purification techniques. Specifically, we focus on strategies for dsRNA removal, which can be broadly categorized into two approaches: (1) separating or removing dsRNA from in vitro transcription (IVT) mRNA products using methods such as RP-HPLC chromatography and cellulose-based purification; and (2) minimizing dsRNA formation during IVT by employing engineered RNA polymerase mutants, chaotropic agents, and magnetic beads, as well as modifying/optimizing DNA templates or RNA molecules to reduce dsRNA generation. We also discuss the advantages and limitations of these purification methods, the factors influencing the selection of purification strategies, and explore potential future directions for improving dsRNA purification technologies and their applications in mRNA-based therapeutics.
Jin-He Liu, Jian Zang, Jingru Xu et al.· Journal of Biomedical Scienc...· 0 citations
