体外
抄写(语言学)
信使核糖核酸
细胞生物学
计算生物学
化学
生物
遗传学
基因
哲学
语言学
作者
Wei He,Xinya Zhang,Yangxiaoyu Zou,Ji Li,Chong Wang,Yu-Cai He,Qiuheng Jin,Jianren Ye
出处
期刊:Molecules
[MDPI AG]
日期:2024-05-23
卷期号:29 (11): 2461-2461
标识
DOI:10.3390/molecules29112461
摘要
mRNA vaccines are entering a period of rapid development. However, their synthesis is still plagued by challenges related to mRNA impurities and fragments (incomplete mRNA). Most impurities of mRNA products transcribed in vitro are mRNA fragments. Only full-length mRNA transcripts containing both a 5′-cap and a 3′-poly(A) structure are viable for in vivo expression. Therefore, RNA fragments are the primary product-related impurities that significantly hinder mRNA efficacy and must be effectively controlled; these species are believed to originate from either mRNA hydrolysis or premature transcriptional termination. In the manufacturing of commercial mRNA vaccines, T7 RNA polymerase-catalyzed in vitro transcription (IVT) synthesis is a well-established method for synthesizing long RNA transcripts. This study identified a pivotal domain on the T7 RNA polymerase that is associated with erroneous mRNA release. By leveraging the advantageous properties of a T7 RNA polymerase mutant and precisely optimized IVT process parameters, we successfully achieved an mRNA integrity exceeding 91%, thereby further unlocking the immense potential of mRNA therapeutics.
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