开启mRNA技术实用化大门的钥匙——浅析2023年度诺贝尔生理学或医学奖  

The key to practical application of mRNA technology:A brief analysis of the 2023 Nobel Prize in Physiology or Medicine

作　　者：杜沛 王奇慧[1] Pei Du;Qihui Wang(Institute of Microbiology,Chinese Academy of Sciences,Beijing 100101,China)

机构地区：[1]中国科学院微生物研究所,北京100101

出　　处：《科学通报》2023年第36期4943-4947,共5页Chinese Science Bulletin

摘　　要：在现代生命的中心法则中,RNA是遗传信息的传递者和重要的调控者.其中,信使RNA(messenger RNA,mRNA)作为中间分子,将DNA编码的信息传递到蛋白质序列,因而在发挥疫苗和药物功能时具备许多独特的优势.从1961年mRNA的发现到2020年新型冠状病毒感染全球大流行期间的mRNA疫苗接种,mRNA技术经历近60年的发展,最终进入了大规模的临床应用阶段.在这一过程的早期,科学家们陆续突破了mRNA的实验室合成、在细胞内表达蛋白质、递送进入动物体内等多种技术,但mRNA自身具有的免疫原性限制了其在人体内的进一步应用,成为了制约mRNA技术实用化的关键技术瓶颈.2023年度诺贝尔生理学或医学奖授予了Katalin Karikó和Drew Weissman,以表彰他们在核苷碱基修饰方面的发现.这一发现使mRNA技术突破了进入人体之后的安全性瓶颈,使得在新型冠状病毒感染大流行期间快速开发出有效mRNA疫苗成为可能.本文将对2023年度诺贝尔生理学或医学奖进行解读,并通过mRNA技术的“前世今生”浅析这一技术的重要意义.The 2023 Nobel Prize in Physiology or Medicine was awarded to Katalin Karikóand Drew Weissman in recognition of their contributions to mRNA technology.Before this groundbreaking discovery,mRNA was known to be unstable and can induce inflammatory reactions.Without overcoming this challenge,the progression of mRNA technology towards clinical applications would be hindered.In 2005,Katalin Karikóand Drew Weissman discovered that,unlike naturally synthesized mRNA,in vitro transcribed mRNA led to adverse inflammatory reactions through the release of pro-inflammatory cytokines after being recognized by dendritic cells(DC)as a foreign molecule and subsequent activation of toll-like receptor 3(TLR3).With this knowledge,they further discovered that,by introducing naturally occurring modified nucleotides to substitute unmodified nucleotides during in vitro transcription,the activation of monocyte-derived dendritic cells(MDDC)induced by mRNA containing these modified nucleotides was significantly reduced and the inflammatory reactions could be nearly eliminated.This discovery has overcome the safety bottleneck of mRNA,unleashing the potential of mRNA technology.In the following years,with more technological breakthroughs in lipid nanoparticle(LNP)-based delivery method and large-scale mRNA production,the advantages of mRNA technology in terms of standardized development,safety,and effectiveness have become evident,and has begun to facilitate new technological breakthroughs in the prevention of infectious diseases and the treatment of cancer,genetic disorders,and autoimmune diseases.For infectious diseases that lack effective vaccines,the advantages of mRNA vaccines have ushered in new approaches to solving challenges such as encoding multiple proteins in a single vaccine and targeting rapidly evolving viruses.In addition to preventing infectious diseases,the characteristic of mRNA to express any protein within the body brought it a flexible“body reprogramming”capability,allowing the intervention for various internal ab

关 键 词：诺贝尔生理学或医学奖 冠状病毒感染 药物功能 中心法则 技术实用化 DNA编码 信息传递 信使RNA 

分 类 号：Q503[生物学—生物化学]