Zhao Yang-Yang, Zhu Fu-Ming, Zhang Yong-Juan, Wei Huanhuan Y
Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Vaccines (Basel). 2025 Jul 31;13(8):821. doi: 10.3390/vaccines13080821.
Circular RNAs (circRNAs) have emerged as a transformative class of RNA therapeutics, distinguished by their closed-loop structure conferring nuclease resistance, reduced immunogenicity, and sustained translational activity. While challenges in pharmacokinetic control and manufacturing standardization require resolution, emerging synergies between computational design tools and modular delivery platforms are accelerating clinical translation. In this review, we synthesize recent advances in circRNA therapeutics, with a focused analysis of their stability and immunogenic properties in vaccine and drug development. Notably, key synthesis strategies, delivery platforms, and AI-driven optimization methods enabling scalable production are discussed. Moreover, we summarize preclinical and emerging clinical studies that underscore the potential of circRNA in vaccine development and protein replacement therapies. As both a promising expression vehicle and programmable regulatory molecule, circRNA represents a versatile platform poised to advance next-generation biologics and precision medicine.
环状RNA（circRNAs）已成为一类具有变革性的RNA疗法，其特点是闭环结构赋予核酸酶抗性、降低免疫原性并具有持续的翻译活性。虽然药代动力学控制和生产标准化方面的挑战需要解决，但计算设计工具和模块化递送平台之间新出现的协同作用正在加速临床转化。在本综述中，我们综合了circRNA疗法的最新进展，重点分析了它们在疫苗和药物开发中的稳定性和免疫原性特性。值得注意的是，还讨论了实现可扩展生产的关键合成策略、递送平台和人工智能驱动的优化方法。此外，我们总结了临床前和新兴的临床研究，这些研究突出了circRNA在疫苗开发和蛋白质替代疗法中的潜力。作为一种有前途的表达载体和可编程调控分子，circRNA代表了一个多功能平台，有望推动下一代生物制品和精准医学的发展。
