This article from the micro-channel public number” Nutshell “(ID: Guokr42), author Wuguai Fortunately, love Fan Er released with permission.

On March 16, 2020, the American biotech company Moderna announced that it had received FDA approval to officially begin clinical trials of a vaccine against the new crown pneumonia virus. The first volunteer has received the first dose of injection in Seattle.

On the second day, the Chinese Academy of Military Sciences also announced that the new crown virus vaccine jointly developed by them and Kangsino Biological Co., Ltd. had been approved by the state.Begin clinical trials of planned vaccines.

Can’t help but say that the speed of this research and development is very impressive, because The virus was found in China, scholars performed isolation and sequencing to publish the virus gene map, and the first volunteer received the injection. In just two months . This was unimaginable before.

▲ First volunteer to receive Moderna Crown vaccine in Seattle | www.washingtonpost.com

Why do you say that? Because the mechanism of traditional vaccines is to make the human body produce antibodies, such as inactivated and inactivated vaccines, it is to inject humans with viruses that reduce pathogenicity and toxicity, or dead viruses or bacteria, to stimulate the body to produce immunity force.

So the first step in making a vaccine is to isolate the disease-causing virus, then cultivate the virus in the laboratory, and then find ways to attenuate or inactivate the virus without losing the role of the vaccine that stimulates the immune system. At the same time, the research and development team also needs to do cell and animal experiments, which is time-consuming and labor-intensive, often taking years or even decades.

So Commonly speaking, this new crown vaccine will be clinically tested after two months, which is really incredible .

▲ Laboratory of Moderna | www.modernatx.com

Captain Marvel in the vaccine

According to clinical trial data published by Moderna, This trial is a brand new mRNA vaccine named vaccine mRNA-1273, not any of the traditional vaccines. It gives people a feeling that they are full of “black technology points” and can reduce the dimensionality of new crown viruses.

What is an mRNA vaccine? It is known that the genetic code of an organism is stored in DNA in the nucleus of a cell. The genetic code of DNA controls all biological activities and directs the cells in the organism to synthesize proteins to ensure and maintain the normal operation of physiological activities. But DNA has only four basic codes, CGAT, and DNA exists in the nucleus, which cannot synthesize proteins.

To translate the DNA code into a protein, RNA is needed. RNA transcribes the DNA’s code (transcription), and then comes out of the nucleus and enters the cytoplasm. The organelles in the cytoplasm translate these 4 basic codes and synthesize amino acids according to the coding instructions of the RNA. Different combinations of amino acids form different proteins.

▲ Transcribed DNA-encoded RNA assists in the synthesis of amino acids to form proteins | www.news-medical.net

A simple analogy, If a vaccine is compared to a missile against viruses, DNA is the original blueprint for the design of the missile, and RNA is for engineers to understand actual drawings that can guide factories how to make missiles Amino acids are components, and proteins are completed missiles.

Previous protein vaccine synthesis required virus extraction, detection of the virus’s genetic code, and synthesis of virus-causing proteins in the laboratory based on the genetic code. When these protein vaccines enter human cells, they activate the immune response inside the cells to form antibodies. To put it plainly, the missile was built at the factory according to the drawings and then put into actual combat. It takes a long time. That mRNA vaccine is a step away from factory production and puts design drawings directly into the battlefield. This new vaccine has the following advantages:

1. Fast development

The so-called “Martial arts in the world, but do not break soon.” Because protein synthesis is not required in vitro, viral pathogenic mRNA fragments can be directly injected through biological meansInto human cells. Human cells directly synthesize viral proteins based on the viral RNA code, directly form an immune response, and synthesize antibodies.

The shortening of the process not only shortens the time, but also saves the steps of testing, regulating and modifying in the process of protein synthesis in vitro. Only the genetic code of the virus is needed to design an mRNA vaccine in a short time. This is the fundamental reason why Moderna can conduct clinical trials so quickly. This is equivalent to throwing the design drawing directly into the cell, allowing the cell to synthesize weapons according to the drawing, and fight the virus, without the need to go out of the factory to slowly build weapons and then put them into the battlefield, saving precious time —— On January 7th, the genetic information published by Chinese scholars was obtained. On January 13th, they designed the first sequence of the mRNA sequence gene coding. On February 24th, the synthetic vaccine was delivered to the test center.

2. Simulate a virus directly

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▲ mRNA carries a genetic code that triggers an immune response | www.wired.com

The mRNA carries the genetic code that stimulates the immune response of the virus. After entering the cell, the human cell regards it as its own genetic information and synthesizes the “weapon” directly according to the drawing. This synthesized “weapon” is more than a “processing plant” in vitro. The synthesis is more “original”, because human cells not only synthesize according to drawings, but also may add natural synthetic correction procedures after synthesis, and further polish the weapon, it may be more accurate and “destructive” .

3. More powerful

The mRNA vaccine can be edited into multiple protein information at the same time. For example, the genetic codes of multiple pathogenic proteins in different parts of the same virus can be programmed and synthesized in the cell at one time to form a more complex and comprehensive vaccine. For example, the cytomegalovirus mRNA vaccine developed by the company edited 6 different mRNA information at the same time to form a more robust vaccine.

4. Easy production

Because traditional vaccines require multiple steps, the synthetic conditions are very strict and it is difficult to mass produce them in a short time. And mRNA vaccines make rapid synthesis possible by eliminating many intermediate processes.

Super weapons also have shortcomings

In this way, the mRNA vaccine is simply a glove full of cosmic energy gems in the hands of annihilation. As long as you hit a cripple, the new crown virus will be wiped out. Isn’t there any disadvantage?

Obviously.

First, to synthesize an mRNA vaccine based on the genetic code of the virus, it is important to choose which piece of genetic information. Because unlike traditional vaccines that have actual viruses as a reference, predicting / designing mRNA vaccines based on biological genetic knowledge is a bit “closed door”. Of course, the huge advances in biology make this kind of “closed-door car construction” target-oriented, but errors still inevitably occur, resulting in the vaccine’s inability to stimulate the immune response.

▲ Computer simulation animation: New coronavirus that enters the body with antibody proteins | https://www.pharmaceutical-business-review.com/

Second, mRNA is not as stable as protein or DNA and is very difficult to save. Especially after entering the body, how to avoid the body’s own immune system and how to not be eliminated by the immune system as a foreign pathogen It is a difficult problem.

Once again, after the mRNA vaccine is synthesized in vitro, how to let it enter human tissues and finally into the target cells, and still maintain the original ability to stimulate the immune response, is also a difficult problem to solve. Even if the mRNA vaccine has escaped the strong immune system of the human body, and has entered the expected cells after “thousands of mountains and rivers, nine dead and a lifetime”, can it deceive the body’s own cells, let it use this section of mRNA as its own genetic code. This drawing of synthetic weapons (antibody proteins) is also difficult to secure. For example, give an external drawing to the factory, expect this factory to be unquestionable, and to synthesize weapons according to the drawing honestly, the risk is very high. Once factory workers become suspicious, not only do they not synthesize weapons, they are also likely to “burn” the drawing directly.

Take a step back and say that if mRNA perfectly avoids the above problems and synthesizes a “super weapon”, no one can guarantee the quality and quantity of the weapon. It is possible to create weapons that are of low quality and quantity. low. Also, is it possible to synthesize an unexpected protein and cause other damage instead?

Therefore, the design of this new type of mRNA vaccine has good ideas and promising prospects, but there are still many difficulties. So far, no mRNA vaccine has passed clinical trials and entered clinical use.

▲ Flowchart of the vaccine after it enters the human body | www.ft.com

Not only that, because the new crown epidemic is fierce, The National Institutes of Health (NIH) has adopted the principle of urgency and simplification. Approval of vaccine development can omit animal experiments and directly perform human tests. Therefore, the development of Moderna’s mRNA vaccine is very rapid, thanks to this special policy. I have to say that this move is not without risks. Although it is disappointing to fail to achieve the expected immune effect, it is not the worst. If unexpected side effects occur and an unwanted immune response is formed, it is the most worrying.

However, according to public information from Moderna, animal experiments are being conducted at the same time as human experiments. Moderna’s mRNA vaccine human trial enrolled 45 volunteers in the first phase. The vaccine was injected twice, with a 28-day interval, mainly to test for toxic and side effects. Although the immune effect will also be checked at the same time, the main purpose is still to test safety. .

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