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.