mRNA vaccines in the prevention and treatment of diseases.
mRNA vaccines in the prevention and treatment of diseases.
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作者：
Gu, Yangzhuo;Duan, Jiangyao;Yang, Na;Yang, Yuxin;Zhao, Xing
尽管 mRNA 疫苗的历史可以追溯到几十年前，但自 2019 年底开始，信使核糖核酸 (mRNA) 疫苗在抗击 COVID-19 疫情的过程中成功首次公开亮相。本综述概述了 mRNA 疫苗开发的历史进程和现状，以及 mRNA 疫苗的一些基本概念。我们讨论了 mRNA 疫苗的一般制备和制造，还讨论了体内递送系统的科学进展，并详细评估了流行的方法（即脂质纳米颗粒和鱼精蛋白）。接下来，我们重点介绍mRNA疫苗作为治疗性治疗的有力候选者的临床价值，并讨论2019年癌症和冠状病毒疾病治疗的临床进展。数据表明，mRNA疫苗具有几个突出的优势，由于在疾病管理方面的巨大潜力，已经取得了令人鼓舞的结果并日益受到关注。最后，我们提出了一些值得进一步研究和优化的潜在方向。除了基础研究外，有助于促进储存和运输的研究对于实际应用也是必不可少的。 mRNA 疫苗治疗传染病和癌症的机制。编码肿瘤抗原的 mRNA 分子被注射到体内（无论有或没有递送载体）。 mRNA 分子被抗原呈递细胞 (APC) 摄取并翻译成蛋白质抗原。经过蛋白酶体加工后，抗原肽与内质网中的 MHC I 类分子结合，并转移到 APC 表面，激活 CD8+ T 细胞以产生特定的细胞免疫反应。根据内体途径分类的蛋白质抗原可以通过 MHC II 类呈递途径激活 CD4+ T 细胞。 mRNA编码的分泌蛋白抗原或膜抗原可以刺激B细胞产生中和抗体，并激活巨噬细胞等吞噬细胞分泌炎症细胞因子，促进循环感染病原体和肿瘤细胞的清除。
Messenger ribonucleic acid (mRNA) vaccines made their successful public debut in the effort against the COVID‐19 outbreak starting in late 2019, although the history of mRNA vaccines can be traced back decades. This review provides an overview to discuss the historical course and present situation of mRNA vaccine development in addition to some basic concepts that underly mRNA vaccines. We discuss the general preparation and manufacturing of mRNA vaccines and also discuss the scientific advances in the in vivo delivery system and evaluate popular approaches (i.e., lipid nanoparticle and protamine) in detail. Next, we highlight the clinical value of mRNA vaccines as potent candidates for therapeutic treatment and discuss clinical progress in the treatment of cancer and coronavirus disease 2019. Data suggest that mRNA vaccines, with several prominent advantages, have achieved encouraging results and increasing attention due to tremendous potential in disease management. Finally, we suggest some potential directions worthy of further investigation and optimization. In addition to basic research, studies that help to facilitate storage and transportation will be indispensable for practical applications. Mechanisms of mRNA vaccines for infectious diseases and cancers. mRNA molecules encoding tumor antigens are injected into body (either with or without delivery vehicles). The mRNA molecules are taken up and translated into protein antigens by antigen‐presenting cells (APCs). After proteasomal processing of proteins, antigen peptides associate with MHC Class I molecule in the endoplasmic reticulum and are transferred to the APC surface, activating CD8+ T cells for a specific cellular immune response. Protein antigens, which are sorted for the endosome route, can activate CD4+ T cells via the MHC Class II presentation pathway. The secretory protein antigen or membrane antigen encoded by mRNA can stimulate B cells to produce neutralizing antibodies and activate phagocytes such as macrophages to secrete inflammatory cytokines, facilitating the clearance of circulating infectious pathogens and tumor cells.
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影响因子：
7.8
作者：
Hamza, Marwa S.;Tikamdas, Rajiv;El Baghdady, Noha S.;Sayed, Moustafa;Elbarazi, Amani S.;Badary, Osama A.;Elmazar, Mohamed M.
通讯作者：
Elmazar, Mohamed M.
影响因子：
4.1
作者：
Asrani, Kirtika H.;Farelli, Jeremiah D.;Brown, Jeffrey M.
通讯作者：
Brown, Jeffrey M.
DOI：
10.1056/nejmoa2035389
发表时间：
2021-02-04
期刊：
The New England journal of medicine
影响因子：
--
作者：
Baden LR;El Sahly HM;Essink B;Kotloff K;Frey S;Novak R;Diemert D;Spector SA;Rouphael N;Creech CB;McGettigan J;Khetan S;Segall N;Solis J;Brosz A;Fierro C;Schwartz H;Neuzil K;Corey L;Gilbert P;Janes H;Follmann D;Marovich M;Mascola J;Polakowski L;Ledgerwood J;Graham BS;Bennett H;Pajon R;Knightly C;Leav B;Deng W;Zhou H;Han S;Ivarsson M;Miller J;Zaks T;COVE Study Group
通讯作者：
COVE Study Group
影响因子：
7.2
作者：
Bol KF;Figdor CG;Aarntzen EH;Welzen ME;van Rossum MM;Blokx WA;van de Rakt MW;Scharenborg NM;de Boer AJ;Pots JM;Olde Nordkamp MA;van Oorschot TG;Mus RD;Croockewit SA;Jacobs JF;Schuler G;Neyns B;Austyn JM;Punt CJ;Schreibelt G;de Vries IJ
通讯作者：
de Vries IJ
影响因子：
5.5
作者：
Aldrich C;Leroux-Roels I;Huang KB;Bica MA;Loeliger E;Schoenborn-Kellenberger O;Walz L;Leroux-Roels G;von Sonnenburg F;Oostvogels L
通讯作者：
Oostvogels L