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环状RNA的成环策略及环状RNA疫苗的研究现状

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环状RNA相比于线性mRNA具有合成简单、稳定性高、持续稳定表达等优点,在感染性微生物疫苗、肿瘤疫苗和蛋白替代疗法等领域具有巨大的应用潜力,近年来已经成为核酸药物领域研究的热点.RNA的环化技术是体外合成环状RNA的关键,成环策略对环化效率、免疫原性和蛋白表达量等产生重要影响,制约了环状RNA的基础研究和临床应用.本文系统综述了化学法、酶法和核酶法等几种成环策略,重点分析各成环技术的反应条件、成环工艺、环化效率和免疫原性等.目前,理想的环状RNA成环策略还面临诸多挑战,但是研究证实环状RNA在新型冠状病毒肺炎疫苗、抗肿瘤疫苗等领域比线性mRNA具有更好的稳定性和更强的免疫效应,成为一种极具潜力的新型核酸药物分子,为优化和拓展环状RNA的研究和临床应用提供参考.
Circular RNA formation strategy and current research status of circular RNA vaccine
Circular RNA has the advantages of a simple synthesis method,high stability,and continuous and stable expression over linear mRNA,and has great potential for application in microbial infection vaccines,tumor vac-cines,protein replacement therapy,etc.In recent years,circular RNA has become a hotspot in the field of nucleic acid drugs.The cyclization technique of RNA is the key to the synthesis of circular RNA in vitro.The cyclization strategy has an important impact on cyclization efficiency,immunogenicity,protein expression,etc.,which limits the basic research and clinical application of circular RNA.This paper provides a systematic review of several cyclization strategies including the chemical method,enzyme method,and ribozyme method.The reaction conditions,cyclization process,cyclization ef-ficiency,and immunogenicity of each cyclization technology were analyzed.At present,the ideal circular RNA formation strategy still faces many challenges.However,studies have confirmed that circular RNA has better stability and stronger immune effects than linear mRNA in the fields of coronavirus disease 2019(COVID-19)vaccine and anti-tumor vaccine.Consequently,circular RNA has become a novel nucleic acid drug molecule with great potential.This research provides valuable insights for optimizing and expanding the research and clinical application of circular RNA.

circular RNAnucleic acid drugRNA vaccinecoronavirus disease 2019

高子寒、魏科

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湖南中医药大学医学院,湖南 长沙 410208

环状RNA 核酸药物 RNA疫苗 新型冠状病毒肺炎(2019冠状病毒病)

湖南省卫生健康委科研项目长沙市杰出创新青年培养计划湖南中医药大学省级学科建设项目(中西医结合)湖南省卫生健康高层次人才湖南中医药大学校级重点科研项目湖南中医药大学校级重点科研项目

D202301067791kq220604720240304114No2024XJZA010

2024

中国病理生理杂志
中国病理生理学会

中国病理生理杂志

CSTPCD北大核心
影响因子:1.065
ISSN:1000-4718
年,卷(期):2024.40(10)