This article is from the WeChat public account: Nutshell (ID: Guokr42) , author: Wuguai Fortunately, the first map from the “Washington Post”
On March 16, 2020, the American biotechnology 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 coronavirus vaccine jointly developed by them and Kangsino Biological Co., Ltd. had obtained national approval to start planning a clinical trial of the vaccine.
We ca n’t help but say that this research and development speed has made a deep impression, because the virus was found in China, scholars performed isolation and sequencing to publish the virus gene map, and the first volunteer received an injection. Two months. This was unimaginable before.
The first volunteer to receive the Moderna New 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 from a common sense, the new crown vaccine will be clinically tested in two months.It was incredible.
Moderna Labs | www.modernatx.com
“Captain Marvel” in the vaccine
According to clinical trial data published by Moderna, this test is a new type of mRNA vaccine named vaccine mRNA-1273, which is not any of the traditional vaccines, giving people a “black technology point” plus Full, the feeling of being able to implement a dimensional reduction blow on the new crown virus.
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 writes down the DNA code into (transcription) , then comes out of the nucleus and enters the cytoplasm. The organelles in the cytoplasm translate and synthesize amino acids according to the coding instructions of RNA. Different combinations of amino acids form different proteins.
Transcription of 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 the actual drawings that can guide factories on 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. The mRNA vaccine is a step away from factory production, and the design drawings are directly put into use on the battlefield. This new vaccine has the following advantages:
1. Fast development
The so-called “Martial arts in the world, but don’t break fast.” Because there is no need to synthesize proteins in vitro, viral-pathogenic mRNA fragments can be directly injected into human cells through biological means. Human cells directly synthesize viral proteins according to 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 drawings directly into the cells, allowing the cells to synthesize weapons according to the drawings, and fight the virus, without the need to go outside the factory to slowly build weapons and put them into the battlefield, saving precious time-January 7 After receiving the genetic information published by Chinese scholars, they designed the first sequence of the mRNA sequence gene coding on January 13, and delivered the synthetic vaccine to the testing center on February 24.
2. Simulate a virus directly
mRNA carries a genetic code for the virus to trigger 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 an in vitro “processing plant” “Synthesis is more” original “, because human cells not only synthesize according to drawings, but may also add natural post-synthesis correction procedures after synthesis to further polish the weapon, which 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 to produce
Because traditional vaccines require multiple steps, the synthetic conditions are very strict and it is difficult to produce them in a short period of 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 click your finger, the new crown virus will die out. Isn’t there any disadvantage?
Obviously.
First, to synthesize an mRNA vaccine according to the genetic code of the virus, it is important to choose which piece of genetic information. Because notLike traditional vaccines with actual viruses as a reference, the genetic knowledge of biology to predict / design mRNA vaccines is a bit “closed door”. Of course, the huge advances in biology make this kind of “closed door construction” not unreasonable, but errors are still unavoidable, resulting in the vaccine’s inability to stimulate the immune response.
Computer simulation animation: New crown virus that enters the body with antibody proteins | https://www.pharmaceutical-business-review.com/
Secondly, 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 prevent it from being eliminated by the immune system as a foreign pathogen 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 entered the expected cells after “thousands of mountains and rivers, nine dead and a lifetime”, will it be able to fool the human body’s own cells, letting this mRNA be used as its own genetic code, This drawing synthetic weapon (antibody protein) is also difficult to guarantee. 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 the mRNA perfectly avoids the above problems and synthesizes a “super weapon”, but no one can guarantee the quality and quantity of the weapon. It is possible that the weapon will be of low quality. , And the number is low. Also, is it possible to synthesize an unexpected protein and cause other damage instead?
So, thisThe design of new-type mRNA vaccines 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 body | www.ft.com
Not only that, because the new crown epidemic is fierce, the National Institutes of Health (NIH) approved the principle of urgency and simplicity. Vaccine development can omit animal experiments and perform human tests directly. Therefore, the development of Modernna’s mRNA vaccine is very fast, 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 the information disclosed by Moderna, animal experiments are being conducted at the same time as human experiments. Moderna’s mRNA vaccine human trial, 45 volunteers were recruited 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 is also checked, the main purpose is still to test safety .
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