Nobel Prize Awarded to mRNA Vaccine Scientists ｜mRNA疫苗科学家获得诺贝尔奖

Nobel Prize Awarded to mRNA Vaccine Scientists
诺贝尔奖授予mRNA疫苗科学家

By Yasemin Saplakoglu

October 2, 2023

Katalin Karikó and Drew Weissman have been awarded the 2023 Nobel Prize in Physiology or Medicine for discoveries leading to mRNA vaccines, such as those that protect against Covid-19.

The Nobel Committee has awarded the 2023 Nobel Prize in Physiology or Medicine to Katalin Karikó and Drew Weissman for their pioneering work in the development of mRNA vaccine technology, which made possible a timely vaccine response to the Covid-19 pandemic. Vaccines against the SARS-CoV-2 virus are credited with helping to curb the spread of the pandemic and with saving between 14.4 million and 19.8 million lives in just the first year of their use; mRNA vaccines played a major role in that accomplishment.
诺贝尔委员会已将2023年的诺贝尔生理学或医学奖授予Katalin Karikó和Drew Weissman,以表彰他们在mRNA疫苗技术开发方面的开创性工作,这使得对Covid-19大流行的及时疫苗反应成为可能。针对SARS-CoV-2病毒的疫苗被认为有助于遏制大流行病的传播,并在其使用的第一年就挽救了大约1440万至1980万的生命;mRNA疫苗在这一成就中发挥了重要作用。

For decades, scientists from around the world pursued the use of mRNA (messenger RNA) in medicine. Cells naturally use mRNA, based on genetic DNA, as instructions for making proteins. Researchers aimed to develop tools to create novel mRNA sequences — ones that code for viral proteins, for example — in the lab, and then introduce those mRNA molecules into cells. The cells would then translate these mRNA sequences into viral proteins, thereby alerting the immune system so it would mount a defense against the virus. In effect, the mRNA vaccine turns cells into factories for viral proteins as a strategy for fighting off viral attackers.
几十年来,来自世界各地的科学家一直在追求将mRNA(信使RNA)应用于医学。细胞自然地使用基于遗传DNA的mRNA作为制造蛋白质的指令。研究人员旨在开发工具来在实验室中创建新的mRNA序列 - 例如编码病毒蛋白的序列,然后将这些mRNA分子引入到细胞中。然后,细胞会将这些mRNA序列翻译成病毒蛋白,从而警告免疫系统以便它对抗病毒。实际上,mRNA疫苗将细胞转变为病毒蛋白的工厂,作为抵抗病毒攻击的策略。

However, the first attempts to use mRNA to produce an immune response failed because cells too readily recognized the introduced mRNA molecules as invaders and destroyed them.
然而,最初尝试使用mRNA来产生免疫反应的努力失败了,因为细胞过于容易将引入的mRNA分子识别为入侵者并将其销毁。

In 2005, while working together at the University of Pennsylvania, Karikó and Weissman discovered a way to slightly tweak the nucleotide sequence of the mRNA molecules so that they could sneak past cellular immune surveillance and avoid kicking up a massive inflammatory response. They went on to show in 2008 and 2010 that modified mRNA molecules could produce high levels of proteins. These breakthroughs made mRNA technology usable for creating safe and effective vaccines.
在2005年,Karikó和Weissman在宾夕法尼亚大学共同工作时,发现了一种微调mRNA分子的核苷酸序列的方法,使它们能够偷偷绕过细胞免疫监视,避免引发大规模的炎症反应。他们在2008年和2010年进一步证明,修改后的mRNA分子能够产生高水平的蛋白质。这些突破使mRNA技术可用于创建安全有效的疫苗。

Within 15 years, the methods were proved on the global stage. By early 2021, barely a year after the Covid-19 pandemic first erupted around the world, multiple pharmaceutical companies had used Karikó and Weissman’s mRNA tools to roll out vaccines against the virus. The pandemic served as a proof of concept for the vaccines, and their success helped pull the world out of the pandemic’s deadliest phase.
在15年内,这些方法在全球范围内得到了证明。到2021年初,仅在Covid-19大流行病在全球爆发一年后,多家制药公司已经使用了Karikó和Weissman的mRNA工具来推出针对该病毒的疫苗。这场大流行病成为了疫苗的概念验证,而它们的成功帮助世界走出了大流行病最致命的阶段。

Karikó and Weissman’s discoveries “fundamentally changed our understanding of how mRNA interacts with our immune system and had a major impact on our society during the recent Covid-19 pandemic,” said Rickard Sandberg, a member of the Nobel Committee, during this morning’s announcement. Vaccines, both of the conventional and mRNA varieties, “have saved millions of lives, prevented severe Covid-19, reduced the overall disease burden and enabled societies to open up again.”
Karikó和Weissman的发现“从根本上改变了我们对mRNA如何与我们的免疫系统交互的理解,并在最近的Covid-19大流行期间对我们的社会产生了重大影响,”诺贝尔委员会成员Rickard Sandberg在今天早上的公告中说。无论是传统的还是mRNA的疫苗,“都挽救了数百万人的生命,防止了严重的Covid-19,减轻了总体疾病负担,并使社会得以再次开放。”

What is mRNA?什么是mRNA?

Messenger RNA is a single strand of genetic code that the cell uses as instructions to make proteins. These mRNA molecules are native to cells and are key parts of everyday cellular functions: They are the messengers that carry transcribed DNA sequences out of the protected nucleus and into the cell cytoplasm, where they can be translated into proteins by the organelles called ribosomes. A ribosome reads the strand, translating groupings of genetic letters into sequences of amino acids. The long string of amino acids that results then folds into the appropriate protein.
信使RNA是一条单链的遗传代码,细胞用它作为制造蛋白质的指令。这些mRNA分子是细胞的固有部分,是日常细胞功能的关键部分:它们是将转录的DNA序列从受保护的核心传递到细胞质中的信使,这样它们就可以被称为核糖体的细胞器翻译成蛋白质。核糖体读取这条链,将遗传字母的组合翻译成氨基酸的序列。然后,产生的长串氨基酸折叠成适当的蛋白质。

How do mRNA Covid-19 vaccines work?
mRNA Covid-19疫苗是如何工作的?

Scientists have learned to write mRNA code to form novel proteins — including proteins that can help cells recognize viruses they’ve never seen. The mRNA technology developed by the Nobel Prize winners borrows the cells’ protein-making machinery, inducing cells to produce viral proteins that prime the immune system to recognize a given virus if they encounter it later.
科学家已经学会编写mRNA代码以形成新的蛋白质 - 包括可以帮助细胞识别他们从未见过的病毒的蛋白质。由诺贝尔奖获得者开发的mRNA技术借用了细胞的蛋白质制造机器,诱导细胞产生病毒蛋白,以便在以后遇到特定病毒时,免疫系统能够识别它。

When smuggled into cells inside lipid nanoparticle capsules, the mRNA elements deliver the recipe for making the SARS-CoV-2 “spike” protein, which is found on the outside surface of the virus. Cells then use those instructions to produce the spike protein as if they had been infected by the real virus. It’s like an immunity practice round: The mRNA primes the immune system to recognize an actual SARS-CoV-2 spike protein, so that if a person is later exposed to the virus, the immune system will quickly “remember” how to kick up a response to fight it.
当mRNA元素被走私到脂质纳米颗粒胶囊内的细胞中时,它们会提供制作SARS-CoV-2“刺突”蛋白的配方,这种蛋白质位于病毒的外表面。然后,细胞会使用这些指令来产生刺突蛋白,就好像它们已经被真正的病毒感染了一样。这就像是免疫系统的一次实战演练:mRNA会使免疫系统预先认识到真正的SARS-CoV-2刺突蛋白,这样,如果一个人后来暴露于病毒,免疫系统会迅速“记住”如何启动反应来对抗它。

What was the breakthrough that led to the success of the vaccines?
是什么突破导致了疫苗的成功?

In the early 2000s, a major obstacle to the mRNA technology was that it triggered a major inflammatory response in cells. Cells recognized the introduced mRNA as foreign material and tried to get rid of it, putting cellular defense systems into overdrive. After realizing that cells often modify their own native mRNA, Karikó and Weissman decided to see what would happen if they also slightly tweaked the genetic code of the mRNA they were introducing.
在2000年初,mRNA技术的一个主要障碍是它在细胞中引发了重大的炎症反应。细胞将引入的mRNA识别为外来物质,并试图将其排除,使得细胞防御系统过度运转。在意识到细胞经常修改自己的原生mRNA后,Karikó和Weissman决定看看如果他们也稍微调整他们引入的mRNA的遗传代码会发生什么。

In a breakthrough discovery published in 2005, they reported that the inflammatory response had all but disappeared. In the years that followed, they showed that such tweaks could also greatly increase the number of proteins that the cells could make based on the mRNA sequence.
在2005年发表的一项突破性发现中,他们报告说炎症反应几乎完全消失了。在随后的几年里,他们展示了这样的调整也能大大增加细胞根据mRNA序列能够制造的蛋白质数量。

Were mRNA vaccines used to fight illnesses before the pandemic?
在大流行病之前,mRNA疫苗是否被用来对抗疾病?

A number of companies and researchers tested the promise of mRNA vaccines prior to the pandemic to fight viruses such as Zika and MERS-CoV, which is similar to SARS-CoV-2. But none of the vaccines had been approved for public use as of 2020, when the Covid-19 pandemic erupted. The successful deployment of mRNA vaccines during the pandemic proved the concept of the technology and became a springboard for encouraging its use to prevent or treat other ailments.
在大流行病之前,许多公司和研究人员测试了mRNA疫苗对抗诸如寨卡和MERS-CoV等病毒的承诺,这与SARS-CoV-2相似。但是,截至2020年,当Covid-19大流行病爆发时,还没有任何疫苗被批准用于公众使用。在大流行病期间成功部署mRNA疫苗证明了这项技术的概念,并成为鼓励使用它来预防或治疗其他疾病的跳板。

What are the benefits of mRNA vaccines over more traditional ones?
mRNA疫苗相比传统疫苗有哪些优势?

The promise of mRNA vaccines is that they can be developed easily and quickly. It typically takes more time — on the timescale of years — for scientists to create and test traditional vaccines, which are often a weakened or denatured version of a real virus. And even after a traditional vaccine is developed, scientists must clear a second hurdle — learning how to grow large volumes of virus or protein in the lab — before they can produce the vaccine on the mass scale required to immunize millions or billions of people.
mRNA疫苗的承诺在于它们可以轻松快速地开发出来。科学家通常需要更多的时间——在年的时间尺度上——来创建和测试传统的疫苗,这些疫苗通常是真实病毒的弱化或变性版本。即使在开发出传统疫苗后,科学家们还必须清除第二个障碍——学习如何在实验室中大量培养病毒或蛋白质——才能在需要免疫数百万或数十亿人的大规模生产疫苗。

In 2020, as soon as researchers published the structure and genetic code of the SARS-CoV-2 spike protein, researchers got to work. Within several months, the pharmaceutical giants Pfizer and Moderna had used mRNA technology to develop vaccines that immunized against the virus. They were able to rapidly mass-produce mRNA vaccine, lead clinical trials to prove that the vaccines were safe and effective, and then administer the first jabs to the public by spring 2021. This was possible because mRNA tools can be used to generate a wide variety of proteins without the need to cultivate new methods for growing viruses at a mass scale.
在2020年,研究人员一旦公布了SARS-CoV-2刺突蛋白的结构和遗传代码,研究工作就立即展开。在几个月内,制药巨头辉瑞和摩德纳利用mRNA技术开发出了可以免疫该病毒的疫苗。他们能够迅速大规模生产mRNA疫苗,进行临床试验以证明疫苗的安全性和有效性,然后在2021年春季向公众提供第一剂疫苗。这是因为mRNA工具可以用来生成各种各样的蛋白质,而无需培养新的大规模病毒生长方法。

How will mRNA vaccines be used now?
现在将如何使用mRNA疫苗?

As Sandberg noted in his remarks at the Nobel Prize announcement, “The successful mRNA vaccines against Covid-19 have had a tremendous impact on the interest in mRNA-based technologies.” mRNA technologies are now being used to develop therapeutic protein delivery systems and cancer treatments, as well as vaccines against other infectious diseases.
正如桑德伯格在诺贝尔奖公告中的发言所指出的,“针对Covid-19的成功的mRNA疫苗对mRNA基础技术的关注产生了巨大的影响。” mRNA技术现在被用来开发治疗性蛋白质输送系统和癌症治疗方法,以及针对其他传染病的疫苗。