DNA editing is risky
Speaking of the most popular field in biology today, non-gene editing is none other than gene editing. Genes are the “ultimate code” of all organisms, including humans. If we master the method of modifying genes, we can modify various traits such as tall, short, fat, thin, IQ, and life span of ourselves and our offspring.
Now, the most commonly used gene editing method is called the CRISPR/Cas9 system, which is a method found in bacteria.
When a virus invades bacteria, in order to remember it, the bacteria will integrate a piece of virus DNA into their own chromosomes. We call these virus “business cards” collected by the bacteria CRISPR. CRIS PR uses segments of the same repetitive short DNA (repetitive sequences) to separate the viral DNA. When the same virus invades again, the repetitive sequence closest to the viral DNA will be activated, creating a pair of “molecular scissors” (called “molecular scissors”). It is the protease of Cas), which can cut the subsequent invading virus DNA.
Therefore, CRISPR/Cas is a powerful tool for gene editing, which can be used to edit genes accurately. Scientists can cut and edit the target DNA with the participation of guide RNA and Cas9 protein by installing a repetitive sequence in front of the DNA to be edited.
But we don’t dare to change human genes easily at present, because once the modification is wrong, not only the desired effect will not be achieved, but also uncontrollable evil results may occur, and there is no chance of repentance, which is terrible. . Is there a more secure way?
RNA editors compete for posts
Let us first take a look at the process by which the genetic code takes effect. Gene-DNA fragment uses itself as a template to produce a piece of RNA fragment that is paired with it. RNA is the direct provider of genetic code, which guides the synthesis of protein so that the code finally takes effect, while RNA does its job and retreats silently break down. Since RNA can also provide the genetic code, can we “tamper” the RNA code halfway through, can it also change the traits of organisms?
In fact, almost all organisms will “tamper” R NA, and the duplicate R NA is not exactly the same as the original template DNA. For example, there are some “decorative” fragments on DNA that are not involved in coding. We call them introns. After RNA copies the DNA, these introns are cut off. For another example, some passwords on RNA will have minor changes.
Joshua Rosenthal, a physiologist at the Woods Hole Oceanographic Institution in the United States, was studying the neural activity of marine animals such as squid and octopus and found that the electrical signals transmitted in the same animal often change, making it difficult for him to draw a unified Electrical signal diagram. The DNA encoding the nervous system has not changed. Why does the electrical signal change? Later, he finally found the reason. It turned out that the RNA codes in squids and octopuses are often changed. After the RNA is changed, the proteins produced will also change, so the electrical signals transmitted by the nervous system are also different.
Since changing RNA can also change some biological traits, how can we make RNA change according to our ideas? We can refer to DNA editing methods to edit RNA.
In addition to the Cas enzyme unique to bacteria, the most common RNA editing enzyme in organisms is actually A DA R, and humans also use A DA R enzymes to modify RNA. However, the original ADAR enzymes in people’s bodies have very limited effects and can only cut and change specific RNAs. Scientists modeled the CRISPR/Cas9 system to create a system called CIRTS. With this system, scientists can make ADAR enzymes replace Cas enzymes to cut arbitrary Target RNA, freely edit RNA.
RNA editors show their talents
Found a way to freely edit RNA, and now the “editors” can’t wait to get into work.
After Rosenthal discovered the “little secret” of the squid’s nerve activity, he began to try to modify the neural pathways of humans. Scientists have discovered that a gene called Nav1.7 determines our pain sensitivity. When it is highly active, it can quickly transmit pain signals to the brain, so that we will have “skin-cutting pain.” When suffering pain, you may prefer this gene inactivation instead of pain, but pain is a line of defense that protects our lives. If we do not perceive small pain, then we will be unable to react to greater danger. Therefore, the pain sensation cannot disappear permanently, but now Rosenthal can make the pain sensation disappear for a longer period of time. He can reduce the control ability of the Nav1.7 gene for a period of time by editing RNA in the painful tissue. This is good news for people who suffer from long-term and severe pain such as pregnancy and gunshot wounds.
Zhang Feng’s team at the Massachusetts Institute of Technology in the United States can reduce the risk of Alzheimer’s disease by editing RNA. The APOE4 gene is a genetic risk factor for Alzheimer’s disease. People with this gene have a higher incidence of disease, but its alleles (different subtypes of the same gene with the same function) APOE2 do not have this. Kind of risk of disease. Feng Zhang’s team edited the RNA produced by the APOE4 gene, and converted the two bases C that are at risk of causing disease into U, so that this RNA is transformed into the harmless APOE2 gene RNA, which does not affect its normal physiology. Function also eliminates pathogenicity.
Immunologist Nina Papavasilio of the Cancer Research Center in Heidelberg, Germany, also sees the potential of RNA editing to treat cancer. An important feature of cancer is that cancer cells have the ability to be immortal and proliferate wildly. This is because cancer cells can close the signaling pathways that inform cell death and stop “suicide.” If RNA editing can be used to invalidate the shutdown signal released by cancer cells and allow the cell’s “suicide” pathway to restore its normal function, the cancer can be cured without medicine.
The two “editors” each have their own strengths
Seeing this, you may not wait to protest. What RNA editing can do, DNA editing can do it a long time ago, and it can do better to ensure that the disease never recurs. In addition to disease treatment, it can also make a facelift and prolong life. With so many advantages of DNA editing, why bother to edit RNA.
It is precisely because of the outstanding advantages of DNA editing that RNA editing has been neglected for decades, until it is discovered that DNA editing is not suitable for humans. The Cas enzyme most commonly used in DNA editing comes from bacteria, and it will cause an immune response when used in humans. The greater hidden danger is that DNA editing is lifelong and will be passed on to future generations. Once editing errors or unexpected side effects occur, it will Cause irreparable damage.
And RNA editing can make up for these shortcomings of DNA editing. ADAR enzyme is the original enzyme in the human body, it does not cause an immune response; RNA is a copy of DNA, as long as DNA exists, it can reproduce hundreds of copies of RNA at any time, so the body does not cherish it. After finishing the protein synthesis work, RNA will be eliminated. The same is true for the modified RNA. Even if the modification is wrong, the human body can easily destroy the modified RNA and the protein it produces, which will not cause any impact on the human body. After removing the unsatisfactory RNA, it is enough to produce “secondary modification” RNA.
Of course, compared with the magical DNA editing, the rising star RNA editing still has many shortcomings, but compared to the “one-time finalization” DNA editing, the “allowing repentance” RNA editing may enter human life faster and cause many deaths. The disease brings new light.