mRNA疫苗及其进展
mRNA疫苗，其化学本质为一条单链RNA分子，与对应DNA碱基互补。不同于传统疫苗数月的生产过程，因其核酸的化学本质，mRNA疫苗易于快速大规模生产【1】。在设计合成后，mRNA被包裹进入纳米颗粒并递送至细胞内；在细胞质中mRNA经由翻译过程，产生引发免疫反应的蛋白质抗原【2】。在新冠疫情爆发前，针对艾滋病毒（HIV-1）、狂犬病毒（Rabies）、寨卡病毒（Zika）和流感病毒（Influenza）的mRNA疫苗已经进入临床试验，此外针对多种血液和实体瘤的mRNA疫苗项目也已开展【3】。新冠疫情爆发后，辉瑞（Pfizer）和德国生物新技术公司（BioNTech）联合研发了针对SARS-CoV-2病毒的mRNA疫苗--BTN162b2，其在细胞内产生的是SARS-CoV-2病毒的Sipke蛋白的受体结合域（RBD区）蛋白【4】。同时，莫德纳公司（Moderna）与国家过敏和传染病研究所（National Institute of Allergy and Infectious Diseases）也启动针对新冠病毒的mRNA疫苗研发，其成果mRNA-1273模拟的是处于预融合（pre-fusion）构象的Spike蛋白【5】。研究证明，针对新冠病毒的mRNA具有很好的安全性和有效性。
mRNA疫苗的五大关键质量属性（Critical Quality Attributes, CQA）
（1）5端加帽结构和效率
（2）非翻译区（UTR）结构、长度
（3）编码区（CDS）序列的修饰
（4）Poly-A-尾特性
（5）mRNA纯度
针对mRNA疫苗研发、生产中所需原料，维百奥（北京）生物科技有限公司开发了一系列高质量原料。包括：修饰核苷酸、生产用酶、预制mRNA等。
mRNA疫苗研发所需的修饰核苷酸
| 产品名称 | 中文名称 | 产品货号 |
| ARCA Cap Analog Sodium Salt, 100mM | ARCA帽类似物钠盐, 100mM | NBM001 |
| ARCA Cap Analog Sodium Salt, Solid | ARCA帽类似物钠盐, 固体 | NBM002 |
| 5-Methyl-CTP Sodium Salt, 100mM | 5-甲基-胞嘧啶核苷三磷酸钠, 100mM | NBM003 |
| N6-Methyl-ATP Sodium Salt, 100mM | N6-甲基-腺嘌呤核苷三磷酸钠, 100mM | NBM004 |
| 2-Thio-UTP Sodium Salt, 100mM | 2-硫-尿嘧啶核苷三磷酸钠, 100mM | NBM005 |
| Pseudo UTP Sodium Salt, 100mM | 假尿嘧啶核苷三磷酸钠，100mM | NBM006 |
| N1-Methylpseudo-UTP Sodium Salt, 100mM | N1-甲基-假尿嘧啶核苷三磷酸钠 | NBM007 |
| 5-Methoxy-UTP Sodium Salt, 100mM | 5-甲氧基-尿嘧啶核苷三磷酸钠, 100mM | NBM008 |
| N1-Methyl-ATP Sodium Salt, Solid | N1-甲基-腺嘌呤核苷三磷酸钠, 100mM | NBM009 |
| N1-Methyl-ATP Sodium Salt, 100mM | N1-甲基-腺嘌呤核苷三磷酸钠, 固体 | NBM010 |
| N4-Acetyl-CTP Sodium Salt, 100mM | N4-乙酰基-胞嘧啶核苷三磷酸钠, 100mM | NBM011 |
预制mRNA
| 产品名称 | 规格 | 产品货号 |
| Premade Haemagglutinin [Influenza A virus (A/Puerto Rico/8/1934(H1N1))] mRNA | 1mg; 5*1mg; 10*1mg | NFM001 |
| Premade Haemagglutinin [Influenza A virus (A/New York/392/2004(H3N2))] mRNA | 1mg; 5*1mg; 10*1mg | NFM002 |
| Premade Haemagglutinin [Influenza A virus (A/California/07/2009(H1N1))] mRNA | 1mg; 5*1mg; 10*1mg | NFM003 |
| Premade Haemagglutinin [Influenza A virus (A/goose/Guangdong/1/1996(H5N1))] mRNA | 1mg; 5*1mg; 10*1mg | NFM004 |
| Premade Haemagglutinin [Influenza B virus (B/Lee/1940)] mRNA | 1mg; 5*1mg; 10*1mg | NFM005 |
| Premade Haemagglutinin [Influenza A virus (A/Shanghai/02/2013(H7N9))] mRNA | 1mg; 5*1mg; 10*1mg | NFM006 |
| Premade Haemagglutinin [Influenza A virus (A/Korea/426/1968(H2N2))] mRNA | 1mg; 5*1mg; 10*1mg | NFM007 |
| Premade Haemagglutinin [Influenza A virus (A/Hong Kong/1073/99(H9N2))] mRNA | 1mg; 5*1mg; 10*1mg | NFM008 |
| Premade Neuraminidase [Influenza A virus (A/Puerto Rico/8/1934(H1N1))] mRNA | 1mg; 5*1mg; 10*1mg | NFM009 |
| Premade Neuraminidase [Influenza A virus (A/goose/Guangdong/1/1996(H5N1))] mRNA | 1mg; 5*1mg; 10*1mg | NFM010 |
| Premade Neuraminidase [Influenza A virus (A/New York/392/2004(H3N2))] mRNA | 1mg; 5*1mg; 10*1mg | NFM011 |
| Premade Neuraminidase [Influenza A virus (A/Shanghai/02/2013(H7N9))] mRNA | 1mg; 5*1mg; 10*1mg | NFM012 |
| Premade Neuraminidase [Influenza A virus (A/California/07/2009(H1N1))] mRNA | 1mg; 5*1mg; 10*1mg | NFM013 |
| Premade Neuraminidase [Influenza A virus (A/Hong Kong/1073/99(H9N2))] mRNA | 1mg; 5*1mg; 10*1mg | NFM014 |
| Premade Neuraminidase [Influenza A virus (A/Korea/426/1968(H2N2))] mRNA | 1mg; 5*1mg; 10*1mg | NFM015 |
| Premade Neuraminidase [Influenza B virus (B/Lee/1940)] mRNA | 1mg; 5*1mg; 10*1mg | NFM016 |
| Premade Nucleoprotein [Influenza A virus (A/Puerto Rico/8/1934(H1N1))] mRNA | 1mg; 5*1mg; 10*1mg | NFM017 |
| Premade Nucleoprotein [Influenza A virus (A/Korea/426/1968(H2N2))] mRNA | 1mg; 5*1mg; 10*1mg | NFM018 |
| Premade Nucleoprotein [Influenza C virus (C/Ann Arbor/1/50)] mRNA | 1mg; 5*1mg; 10*1mg | NFM019 |
| Premade Nucleoprotein [Influenza A virus (A/Hong Kong/1073/99(H9N2))] mRNA | 1mg; 5*1mg; 10*1mg | NFM020 |
| Premade Nucleoprotein [Influenza D virus (D/swine/Oklahoma/1334/2011)] mRNA | 1mg; 5*1mg; 10*1mg | NFM021 |
| Premade Nucleoprotein [Influenza B virus (B/Lee/1940)] mRNA | 1mg; 5*1mg; 10*1mg | NFM022 |
| Premade Nucleoprotein [Influenza A virus (A/New York/392/2004(H3N2))] mRNA | 1mg; 5*1mg; 10*1mg | NFM023 |
| Premade Nucleoprotein [Influenza A virus (A/goose/Guangdong/1/1996(H5N1))] mRNA | 1mg; 5*1mg; 10*1mg | NFM024 |
| Premade Nucleoprotein [Influenza A virus (A/Shanghai/02/2013(H7N9))] mRNA | 1mg; 5*1mg; 10*1mg | NFM025 |
| Premade Nucleoprotein [Influenza A virus (A/California/07/2009(H1N1))] mRNA | 1mg; 5*1mg; 10*1mg | NFM026 |
Reference
【1】IDSOCIETY.ORG
【2】RNA Biol. 2012 Nov 1; 9(11): 1319–1330.
【3】Nature Reviews Drug Discovery volume 17, pages261–279 (2018)
【4】N Engl J Med 2020; 383:2439-2450
【5】N Engl J Med 2020; 383:1920-1931
