Abstract Circular RNA (circRNA) is a candidate for next-generation messenger RNA therapeutics owing to its remarkable stability. Here we describe trans -splicing-based methods for the synthesis of circRNAs over 8,000 nucleotides. The methods are independent of bacterial sequences, outperform the permuted intron–exon method and allow for the incorporation of RNA modifications. The resulting unmodified circRNAs, which incorporate sequences from human 28S ribosomal RNA, display low immunogenicity and are translated more efficiently than permuted intron–exon-derived circRNAs. Additionally, by using viral internal ribosomal entry sites for rolling circle translation, we show that ribosomes can efficiently read through highly structured internal ribosomal entry sites, enhancing the efficiency of rolling circle translation by over 7,000-fold with respect to previous constructs. The efficient and reliable production of circRNA may facilitate its therapeutic use.

Yifei Du

Philipp Konrad Zuber

Huajuan Xiao

Xueyan Li

Yuliya Gordiyenko

V. Ramakrishnan

Nature Biomedical Engineering

NATURE BIOMEDICAL ENGINEERING 于 2017 年 1 月启动，将发表对生物医学工程界具有重要意义的原创研究、评论和评论，包括对设计材料、方法、技术或疗法以了解或对抗疾病感兴趣的实验室科学家；设计或优化医疗设备和程序的工程师；和临床医生利用生物医学工程的研究成果来评估患者健康或在各种临床环境和医疗保健环境中提供治疗。

Nature Biomedical Engineering was launched in January 2017 and aims to publish original research, reviews, and commentaries that are of significant importance to the field of biomedical engineering. The journal focuses on topics such as laboratory research aimed at designing materials, methods, technologies, or therapies to understand or combat diseases; the work of engineers designing or optimizing medical devices and procedures; and how clinicians utilize the findings of biomedical engineering research to assess patient health or provide treatment in various clinical and healthcare settings.

《Nature Biomedical Engineering》于2017年1月创刊，旨在发表对生物医学工程领域具有重要意义的原创研究、评论和综述。期刊关注的主题包括设计材料、方法、技术或疗法，以理解或对抗疾病的实验室科学研究；设计或优化医疗设备和程序的工程师的工作；以及临床医生如何利用生物医学工程的研究成果来评估患者健康，或在各种临床和医疗保健环境中提供治疗。

Category	Quartile
医学	1
医学, 工程生物医学	1

Efficient circular RNA synthesis for potent rolling circle translation

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