Vaccines have been reliably and affordably protecting people from diseases worldwide for centuries. Until the COVID-19 pandemic, however, vaccine development was still a long and idiosyncratic process.
世以，疫苗一直可靠且惠地保全世界的人，免遭疾病侵害。然而，直到2019冠病毒症(COVID-19：Coronavirus Disease-19)大流行病之前，疫苗仍然是一，漫且特殊的程。
Traditionally, researchers had to tailor manufacturing processes and facilities for each vaccine candidate, and the scientific knowledge gained from one vaccine was often not directly transferable to another.
上，研究人必每候疫苗，量身定制生流程及施，且一疫苗得的科知，通常非可直接移到另一疫苗。
But the COVID-19 mRNA vaccines brought a new approach to vaccine development that has far-reaching implications for how researchers make drugs to treat many other diseases.
不，COVID-19 mRNA疫苗了一，研究人如何造，治多其他疾病的物，具有多深意涵的新疫苗方法。
I am a biochemist, and my lab at UMass Chan Medical School focuses on developing better ways to use mRNA as a drug. Although there are many possibilities for what researchers can use mRNA to treat, some important limitations remain.
我是一名生物化家，我在美塞大氏院的室，著重於更佳的方法，使用mRNA作物。然，研究人所能使用mRNA行的治而言，有多可能性。不，仍存在一些大障。
Better understanding how mRNA-based drugs interact with the immune system and how they are degraded in human cells can help lead to safe, durable and effective treatments for a wide range of diseases.
更深入解，以mRNA基的物，如何免疫系交互作用，及它如何在人胞中被降解。能有助於引出，泛疾病而言，安全、持久且有效的法。
Messenger RNA, or mRNA, is made of four building blocks denoted by the letters A, C, G and U. The sequence of letters in an mRNA molecule conveys genetic information that directs how a protein is made.
也就是mRNA的信使RNA，是由字母 A、C、G 及U表示的四材成。mRNA分子中的字母(基)序列，指示蛋白如何造的息。
An mRNA drug comprises two essential components: mRNA molecules, which code for desired proteins, and the lipid molecules – such as phospholipids and cholesterol – that encapsulate them. These mRNA-lipid nanoparticles, or LNPs, are tiny spheres about 100 nanometers in diameter that protect mRNA from degradation and facilitate its delivery into target cells.
mRNA物包含基本成分：渴望之蛋白指定的mRNA分子，及如磷脂及固醇等，封包它的脂分子。此些mRNA脂的奈米粒子，也就是LNPs是保mRNA免於降解，及促其送至的胞，直大100奈米的微小球。
Once inside cells, mRNA molecules instruct the cell’s machinery to produce the target protein required for a desired therapeutic effect. For example, the mRNA in the Pfizer-BioNTech and Moderna COVID-19 vaccines directs cells to produce a harmless version of the virus’ spike protein that trains the immune system to recognize and better prepare for potential infection.
一旦入胞，mRNA分子指示胞作部分，生渴望之治效果所需的的蛋白。譬如，美瑞(Pfizer)德生物新技公司(BioNTech)及美莫德(Moderna)COVID-19疫苗中的mRNA，指示胞生病毒之脊突蛋白的害版本、免疫系及更佳地在感染做。
短片址：https://youtu.be/v-NEr3KCug8
The science behind COVID-19 mRNA vaccines has been decades in the making.
2019冠病毒症(COVID-19：Coronavirus Disease-19)mRNA疫苗背後的科一直展了十年。
From a drug development perspective, mRNA drugs offer significant advantages over traditional drugs because they are easily programmable. Hundreds of pounds of mRNA can be made from readily available DNA templates, such that producing a different mRNA drug is as simple as changing the corresponding DNA templates.
物前景，mRNA物露出，超越物的著。因，它易於可指令序列。易可取得的DNA模板，能生百磅的mRNA。，生不同的mRNA物，如同改相的DNA模板般。
More importantly, different mRNA drugs produced by the same set of methods will have similar properties. They will be delivered to the same tissues, trigger similar levels of immune responses and degrade in similar ways. This predictability significantly reduces the development risks and financial costs of developing mRNA drugs.
更重要的是，由同一套方法生的不同mRNA物，具有相似的性。它能被送到相同的，引相似水平的免疫反，且以相似的方式降解。可性著降低了，mRNA物的及成本。
In addition to being easy to program, mRNA drugs have several other unique properties. For example, just like the mRNAs your body naturally produces, therapeutic mRNAs have a short half-life in cells: about one day. As a result, current mRNA technology is ideal for treatments that aren’t meant to last long in the body.
除了易於指令序列之外，mRNA物具有若干其他的特性。譬如，治性mRNA，就如同人自然生的mRNA，於胞中，有短半衰期：大一天。因此，多不被打算，於人持的法而言，前mRNA技是理想之物。
This is why vaccines are popular candidates for mRNA technology: They provide long-term protection against disease after brief exposure to the drug with few side effects. There are currently more than 30 mRNA vaccine candidates, not including vaccines for COVID-19, in clinical trials.
是何多疫苗是mRNA技的普遍候物：在短曝露於此具很少副作用的物後，它提供疾病的期保。目前，不包括COVID-19疫苗，有多於30mRNA疫苗候物，於床中。
Another critical feature of mRNA drugs is their intrinsic ability to stimulate the immune system. This may sound paradoxical – after all, your cells already contain large amounts of mRNAs. Why would other mRNAs activate your immune system? How does your immune system distinguish between self and nonself mRNAs?
mRNA物的另一性特性，是其刺激免疫系的原本固有能耐。竟，起可能很矛盾。人的胞早已具有大量mRNA。何其他mRNA激活人的免疫系？人的免疫系如何分自身非自身的mRNA？
The first reason involves location. Therapeutic mRNAs enter cells using endosomes – sacs made of the cell’s membrane that take in materials from the cel’s environment.
第一原因涉及位置。治性mRNA利用胞(由胞膜成，胞境中，吸入物的囊)，入胞中。
Your immune system can detect mRNA in endosomes because this is usually a sign of an RNA virus infection – cellular mRNAs normally don’t enter endosomes. When your immune system labels therapeutic mRNAs as viral material, it triggers a strong inflammatory response that can lead to severe side effects.
人的免疫系能察胞中的mRNA，因通常是RNA病毒感染的象。胞的mRNA通常不入胞中。人的免疫系，治性mRNA病毒物，引致重副作用的烈炎反。
1. 吞作用是胞外物(如mRNA分子)於胞被吞噬的程。
Endocytosis is the process by which material outside the cell, such as mRNA molecules, is engulfed within the cell.
One solution to this problem is to modify mRNA’s building blocks – specifically, changing the U, or uridine, to its chemical cousins, pseudouridine and N1-methylpseudouridine.
此的一解方法，是修改mRNA的材。特是，U(也就是尿苷)改成其化近似物：假尿苷及N1-甲基假尿苷。
This subtle chemical change prevents the unwanted immune response while allowing the therapeutic mRNA to direct the cell to make the protein it encodes. The 2023 Nobel Prize in physiology or medicine was awarded to the scientists who made this breakthrough discovery. Both the Pfizer-BioNTech and Moderna COVID-19 mRNA vaccines use this technique.
此微的化改防止了，不需要的免疫反，同允治性mRNA指示胞，生其的蛋白。2023年生理暨予了，做出突破性的科家。瑞BioNTech及莫德COVID-19疫苗，使用了技。
The second source of unwanted immune response is impurities from mRNA production. To prepare mRNA from a DNA template, scientists use a protein called RNA polymerase that tends to make a small amount of side product called double-stranded RNA.
不需要之免疫反的第二源，是自mRNA生的。了一DNA模板mRNA，科家使用一，被RNA聚合酶的蛋白。蛋白向生少量，被股RNA的副物。
Unlike mRNA, which is single-stranded, double-stranded RNA has two chains that form a double helix. RNA viruses also form double-stranded RNA when they replicate, and exposing cells to double-stranded RNA can lead to a strong immune response.
不像股mRNA，股RNA具有，形成螺旋的。RNA病毒，它也形成股RNA。因此，胞曝露於股RNA，引出烈的免疫反。
Removing double-stranded RNA is challenging, especially at the industrial scale. Fortuitously, for mRNA vaccines, the residual amount of double-stranded RNA can stimulate the immune system to enhance antibody responses. However, for applications other than vaccines, a cleaner RNA product is necessary to reduce side effects.
移除股RNA具挑性，特是在工模上。幸的是，就mRNA疫苗而言，留量的股RNA能刺激免疫系，增抗反。然而，就多不同於疫苗的用而言，需要更的RNA品，以少副作用。
Although mRNA has the potential to transform drug development for various medical purposes, careful consideration is required to identify targets that align with the technology’s strengths.
然，mRNA具有改物，供各目使用的力。不，需要仔考，技相符的目。
For example, because there is currently a limit to how long mRNA can last in the body, treatments that need a protein to be present for only a short period of time to achieve a lasting therapeutic effect are ideal. One promising example in development is using mRNA that encodes CRISPR-Cas9 gene-editing proteins to knock out genes that cause specific diseases.
譬如，由於目前mRNA，能在人持多，有限。需要一蛋白，存在短，成持久治效果的法，是理想之法。一於中，有指望的例子是使用，CRISPR(CRISPR：Clustered Regularly Interspaced Short Palindromic Repeat，群聚、律性隔的短文)-Cas9(CRISPR associated protein 9，是一在某些菌DNA病毒之免疫防中，起至重要作用的蛋白)的基因之蛋白的 mRNA，剔除致特定疾病的基因。
Researchers are exploring this strategy to develop a single-dose treatment for hereditary transthyretin amyloidosis, a rare genetic disease caused by the accumulation of misfolded proteins in the heart and nerves. This disease is an ideal target for mRNA-based CRISPR gene therapy because the target protein is produced by the liver.
研究人正在探索此策略以一，供因於心及神中，折蛋白累，引之罕性疾病，性甲腺素蛋白粉性使用的量法。疾病是以mRNA基之CRISPR基因法的理想的。因，的蛋白是由肝所生。
Because most drugs pass through the liver, this makes it easier to deliver CRISPR-Cas9 mRNA to its target. In the next few years, a new generation of more precise mRNA-based genome editing therapies will enter clinical trials.
因，大多物通肝。因此，使其更容易CRISPR-Cas9的mRNA 送至其的。於未年，新一代更精之以mRNA基的基因法，入床。
2. 由於引COVID-19(金色)的病毒及其他RNA病毒透胞入胞中，因此mRNA物能引似的免疫反。
Because the virus that causes COVID-19 (gold) and other RNA viruses enter cells through endosomes, mRNA drug impurities can elicit similar immune responses.
For treatments that need a specific protein to be present in the body for long periods of time or need to prompt little to no immune reaction, further advancements in mRNA technology are necessary to extend mRNA’s half-life and eliminate immune-triggering contaminants.
就需要特定蛋白存在於人，或需要乎不引起免疫反的法而言，在mRNA技上，需一步的展，延mRNA的半衰期，及消除免疫力的污染物。
Notable new developments in these areas include using computational algorithms to optimize mRNA sequences in ways that enhance their stability and engineering RNA polymerases that introduce fewer side products that may cause an immune response.
在此些域中，值得注意的新展包括，使用算演算法，以增其定性及工程改造，引少可能引起免疫反之副物的RNA聚合酶方法，最佳化mRNA序列。
Further advancements have the potential to enable a new generation of safe, durable and effective mRNA therapeutics for applications beyond vaccines.
一步的展具有，能使新一代安全、持久且有效的mRNA法，供疫苗以外之多用途使用的力。
址：https://theconversation.com/drugs-of-the-future-will-be-easier-and-faster-to-make-thanks-to-mrna-after-researchers-work-out-a-few-remaining-kinks-215199
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