Research progress on immune mechanism and control strategy of dsRNA impurities in mRNA vaccine

Introduction Double-stranded RNA (dsRNA) is a key impurity of mRNA vaccines prepared by in vitro transcription (IVT) and is primarily transcribed by T7 RNA polymerase. It can trigger innate immunity and induce a series of side effects that may influence the safety of mRNA vaccines.Areas covered This...

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Main Authors: Xinjun Liu, Chaoying Hu, Qian He, Yu Bai, Xuanxuan Zhang, Zhihao Fu, Xiao Ma, Miao Xu, Zhenglun Liang, Qunying Mao
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Expert Review of Vaccines
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Online Access:https://www.tandfonline.com/doi/10.1080/14760584.2025.2510335
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author Xinjun Liu
Chaoying Hu
Qian He
Yu Bai
Xuanxuan Zhang
Zhihao Fu
Xiao Ma
Miao Xu
Zhenglun Liang
Qunying Mao
author_facet Xinjun Liu
Chaoying Hu
Qian He
Yu Bai
Xuanxuan Zhang
Zhihao Fu
Xiao Ma
Miao Xu
Zhenglun Liang
Qunying Mao
author_sort Xinjun Liu
collection DOAJ
description Introduction Double-stranded RNA (dsRNA) is a key impurity of mRNA vaccines prepared by in vitro transcription (IVT) and is primarily transcribed by T7 RNA polymerase. It can trigger innate immunity and induce a series of side effects that may influence the safety of mRNA vaccines.Areas covered This manuscript summarizes dsRNA generation mechanisms and immunity activation and analyzes the current challenges in dsRNA detection and control strategies. Regulatory standards for dsRNA impurities in mRNA vaccines have also been discussed.Expert opinion dsRNA as a critical quality attribute (CQA), the structural heterogeneity of it (including length and structure) and its precise immunomodulatory mechanisms affecting vaccine safety are poorly understood. Regulatory authorities have not released specific standards for dsRNA. Additionally, there is a lack of comparative analysis data on different corporate testing methods. Therefore, to ensure the safety of dsRNA containing mRNA vaccines and improve mRNA-based platforms, it is of great significance to establish standardized detection methods and standards for dsRNA; to design mRNA production with low dsRNA impurities by adopting the quality by design (QbD) approach; and to evaluate the immune stimulation mechanism of dsRNA impurities in mRNA vaccines.
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publishDate 2025-12-01
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series Expert Review of Vaccines
spelling doaj-art-bec2a573d96c4faaa11d7de270c959ae2025-08-20T01:56:29ZengTaylor & Francis GroupExpert Review of Vaccines1476-05841744-83952025-12-0124145746910.1080/14760584.2025.2510335Research progress on immune mechanism and control strategy of dsRNA impurities in mRNA vaccineXinjun Liu0Chaoying Hu1Qian He2Yu Bai3Xuanxuan Zhang4Zhihao Fu5Xiao Ma6Miao Xu7Zhenglun Liang8Qunying Mao9State Key Laboratory of Drug Regulatory Science, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Research Units of innovative Vaccine Quality Evaluation and Standardization, Chinese Academy of Medical Sciences, National institutes for Food and Drug Control, Beijing, ChinaState Key Laboratory of Drug Regulatory Science, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Research Units of innovative Vaccine Quality Evaluation and Standardization, Chinese Academy of Medical Sciences, National institutes for Food and Drug Control, Beijing, ChinaState Key Laboratory of Drug Regulatory Science, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Research Units of innovative Vaccine Quality Evaluation and Standardization, Chinese Academy of Medical Sciences, National institutes for Food and Drug Control, Beijing, ChinaSinovac Life Sciences Co., Ltd., mRNA Vaccine Center, Beijing, ChinaState Key Laboratory of Drug Regulatory Science, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Research Units of innovative Vaccine Quality Evaluation and Standardization, Chinese Academy of Medical Sciences, National institutes for Food and Drug Control, Beijing, ChinaState Key Laboratory of Drug Regulatory Science, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Research Units of innovative Vaccine Quality Evaluation and Standardization, Chinese Academy of Medical Sciences, National institutes for Food and Drug Control, Beijing, ChinaState Key Laboratory of Drug Regulatory Science, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Research Units of innovative Vaccine Quality Evaluation and Standardization, Chinese Academy of Medical Sciences, National institutes for Food and Drug Control, Beijing, ChinaState Key Laboratory of Drug Regulatory Science, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Research Units of innovative Vaccine Quality Evaluation and Standardization, Chinese Academy of Medical Sciences, National institutes for Food and Drug Control, Beijing, ChinaState Key Laboratory of Drug Regulatory Science, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Research Units of innovative Vaccine Quality Evaluation and Standardization, Chinese Academy of Medical Sciences, National institutes for Food and Drug Control, Beijing, ChinaState Key Laboratory of Drug Regulatory Science, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Research Units of innovative Vaccine Quality Evaluation and Standardization, Chinese Academy of Medical Sciences, National institutes for Food and Drug Control, Beijing, ChinaIntroduction Double-stranded RNA (dsRNA) is a key impurity of mRNA vaccines prepared by in vitro transcription (IVT) and is primarily transcribed by T7 RNA polymerase. It can trigger innate immunity and induce a series of side effects that may influence the safety of mRNA vaccines.Areas covered This manuscript summarizes dsRNA generation mechanisms and immunity activation and analyzes the current challenges in dsRNA detection and control strategies. Regulatory standards for dsRNA impurities in mRNA vaccines have also been discussed.Expert opinion dsRNA as a critical quality attribute (CQA), the structural heterogeneity of it (including length and structure) and its precise immunomodulatory mechanisms affecting vaccine safety are poorly understood. Regulatory authorities have not released specific standards for dsRNA. Additionally, there is a lack of comparative analysis data on different corporate testing methods. Therefore, to ensure the safety of dsRNA containing mRNA vaccines and improve mRNA-based platforms, it is of great significance to establish standardized detection methods and standards for dsRNA; to design mRNA production with low dsRNA impurities by adopting the quality by design (QbD) approach; and to evaluate the immune stimulation mechanism of dsRNA impurities in mRNA vaccines.https://www.tandfonline.com/doi/10.1080/14760584.2025.2510335dsRNAmRNAmechanismsinnate immunityimpurities control
spellingShingle Xinjun Liu
Chaoying Hu
Qian He
Yu Bai
Xuanxuan Zhang
Zhihao Fu
Xiao Ma
Miao Xu
Zhenglun Liang
Qunying Mao
Research progress on immune mechanism and control strategy of dsRNA impurities in mRNA vaccine
Expert Review of Vaccines
dsRNA
mRNA
mechanisms
innate immunity
impurities control
title Research progress on immune mechanism and control strategy of dsRNA impurities in mRNA vaccine
title_full Research progress on immune mechanism and control strategy of dsRNA impurities in mRNA vaccine
title_fullStr Research progress on immune mechanism and control strategy of dsRNA impurities in mRNA vaccine
title_full_unstemmed Research progress on immune mechanism and control strategy of dsRNA impurities in mRNA vaccine
title_short Research progress on immune mechanism and control strategy of dsRNA impurities in mRNA vaccine
title_sort research progress on immune mechanism and control strategy of dsrna impurities in mrna vaccine
topic dsRNA
mRNA
mechanisms
innate immunity
impurities control
url https://www.tandfonline.com/doi/10.1080/14760584.2025.2510335
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