Progress and prospects of mRNA-based drugs in pre-clinical and clinical applications  

作　　者：Yingying Shi Meixing Shi Yi Wang Jian You 

机构地区：[1]College of Pharmaceutical Sciences,Zhejiang University,866 Yuhangtang Road,Hangzhou,Zhejiang,P.R.China [2]State Key Laboratory for Diagnosis and Treatment of Infectious Diseases,79 Qingchun Road,Shangcheng District,Hangzhou,Zhejiang,P.R.China [3]The First Affiliated Hospital,College of Medicine,Zhejiang University,79 QingChun Road,Hangzhou,Zhejiang,P.R.China [4]Jinhua Institute of Zhejiang University,498 Yiwu Street,Jinhua,Zhejiang,P.R.China

出　　处：《Signal Transduction and Targeted Therapy》2024年第12期5470-5512,共43页信号转导与靶向治疗(英文)

基　　金：supported by the National Key R&D Program of China(2023YFC340200);the National Natural Science Foundation of China(No.82404520,82273862);the China Postdoctoral Science Foundation(2024M752834);the China National Postdoctoral Program for Innovative Talents(BX20230321).

摘　　要：In the last decade,messenger ribonucleic acid(mRNA)-based drugs have gained great interest in both immunotherapy and nonimmunogenic applications.This surge in interest can be largely attributed to the demonstration of distinct advantages offered by various mRNA molecules,alongside the rapid advancements in nucleic acid delivery systems.It is noteworthy that the immunogenicity of mRNA drugs presents a double-edged sword.In the context of immunotherapy,extra supplementation of adjuvant is generally required for induction of robust immune responses.Conversely,in non-immunotherapeutic scenarios,immune activation is unwanted considering the host tolerability and high expression demand for mRNA-encoded functional proteins.Herein,mainly focused on the linear non-replicating mRNA,we overview the preclinical and clinical progress and prospects of mRNA medicines encompassing vaccines and other therapeutics.We also highlight the importance of focusing on the host-specific variations,including age,gender,pathological condition,and concurrent medication of individual patient,for maximized efficacy and safety upon mRNA administration.Furthermore,we deliberate on the potential challenges that mRNA drugs may encounter in the realm of disease treatment,the current endeavors of improvement,as well as the application prospects for future advancements.Overall,this review aims to present a comprehensive understanding of mRNA-based therapies while illuminating the prospective development and clinical application of mRNA drugs.

关 键 词：DRUGS CLINICAL gained 

分 类 号：R73[医药卫生—肿瘤]