Gene editing technology CRISPR inventor Zhang Feng: custom baby is still far

(Original title: A CRISPR Pioneer on Gene Editing: 'We Shouldn't Screw It Up')

Graphic: Zhang Feng is one of the discoverers of CRISPR technology

Netease Technology News June 9 news, according to foreign media reports, recently "Atlantic Monthly" visited the gene editing technology CRISPR founder Zhang Feng, discussed the technology challenges, future applications and development direction and other issues. Zhang Feng said that there are still many problems that need to be resolved before the technology can be used to treat human diseases.

When many people saw Zhang Feng for the first time, they would be surprised that this pioneer in gene editing technology was so young. The biologist was only 36 years old and his round face with glasses made him look younger. You know, Zhang Feng has already made two discoveries that are expected to win the Nobel Prize.

The most important of these is CRISPR, a genetic editing tool that can accurately alter human DNA. In the media’s publicity, CRISPR has been considered as a potential tool for treating genetic diseases, curing cancer, and creating customized babies.

CRISPR is also the subject of a fierce patent dispute between Zhang Feng’s Broad Institute and Jennifer Doudna’s University of California, Berkeley. Dudner also announced that he has obtained important CRISPR findings. This patent dispute has sparked a controversy, the focus of which is that this scientific breakthrough should be attributed to whom.

At the recent crisprcon conference, Zhang Feng made a keynote speech and mainly discussed the future of this technology. At this meeting, Sarah Zhang, media officer of the "Atlantic Monthly" interviewed Zhang Feng and discussed the future application of this technology.

Sarah Zhang: Say we are the same family name! However, we are not relatives.

Zhang Feng: Yes, this name is very common and it is very good for anonymity.

Sarah Zhang: When did you start to be interested in research biology?

Zhang Feng: I actually don't like biology. It is like identifying different kinds of leaves and classifying things. I am more interested in mathematics, chemistry, and computers. These are the things that are opened and reintegrated.

Sarah Zhang: This sounds a lot like what you did with CRISPR. CRISPR was originally derived from bacteria and was used primarily to cut bacterial DNA. It was first discovered by scientists when they were studying a little-known bacteria. You apply this technique to human cells. It can also cut DNA from human cells. Do you spend a lot of time reading obscure microbiological literature?

Zhang Feng: Google is very good, PubMed is also good, so you can search for different things. The way I look for things is to first have some assumptions or ideas and then search for things related to that assumption. Then read it extensively in this area to see if there is valuable information concerning this issue.

Sarah Zhang: You have worked in the gene therapy laboratory of the university. The development of gene therapy is also quite tortuous. (Gene therapy is the insertion of normal genes into the body of a human with a missing or defective gene; in theory, gene editing with CRISPR can be used to insert, delete, or modify existing genes.) Gene therapy was heavily promoted in the early 1990s, and then After a dark low tide, we finally see that the gene therapy has been approved by the U.S. Food and Drug Administration. Did you walk along this curve? What does it give you about the future of CRISPR?

Zhang Feng: Of course. The first time I heard about gene therapy was on a molecular biology class on Saturday. That was in 1994, or 1995, the potential of gene therapy is very clear. If we can cure diseases on the genetic level, then we can solve many diseases.

So when I was in school, I happened to have a gene therapy lab in Des Moines. They were recruiting volunteers, so I started working there in the second grade. I have been exposed to a variety of gene therapy methods.

One of the major challenges facing gene therapy is delivery. How can we introduce therapeutic genes into different tissues? In the laboratory at that time, people engaged in the study of various viral vectors: Moloney murine leukemia virus, herpes simplex virus, adeno-associated virus, adenovirus. These are the different ways people are exploring the introduction of genes into patients. What is exciting is that researchers are making progress in making it possible.

Then in 1999, bad news came from the University of Pennsylvania.

Sarah Zhang: You mean that Jesse Gelsinger died in clinical trials. The viral delivery used in gene therapy led to a massive immune response to the body and resulted in his death.

Zhang Feng: For everyone in this field, this is a very thought-provoking moment. So, in the past we did not fully understand the delivery system. We do not understand the biological characteristics of these viruses. This also applies to gene editing technology.

Sarah Zhang: What do you think are the challenges of using CRISPR to treat human diseases?

Zhang Feng: The types of conveyor systems we have are still very limited. For many of these diseases, we do not have a suitable delivery system. Now we have access to blood cells, eyes, and perhaps ears. But if we want to do something on a whole body scale, there is no good way yet.

Viruses are the way nature sends matter to cells. This is a method, so we have worked hard to research and explore various viruses that have not yet been used. We also studied things like exosomes, which are the vesicles that cells release to transfer information between cells.

Sarah Zhang: It's also a natural way.

Zhang Feng: It is indeed a natural way. We also collaborate on lipid nanoparticles, liposomes. I think we must take a broad approach to solve this problem in a comprehensive manner. It is likely that different organizations need different approaches.

Sarah Zhang: Which organs are the most difficult to apply CRISPR?

Zhang Feng: I really want to be able to put things into my brain. But a person who is not enough to eat is still unable to pick and choose. You can explore basic biology and find out where nature wants us to go.

Sarah Zhang: When it comes to the brain, your lab has attracted a lot of attention. But your other half of the research is about the brain, especially mental illness.

Zhang Feng: Since I was in college, I have always been interested in the brain. This is the reason why we are now like this. Unfortunately, we know very little about this. I have a real good friend in college. He has mental illness. From that experience, I realized that mental illness is a very real disease. This is not just because this person is very bad in the past, but that these are things we can't really understand. If I can understand it more, I may be able to find a solution.

Sarah Zhang: Mental illness may be the biggest gap in our understanding and influence of biological mechanisms.

Zhang Feng: Yes, that's right. Part of the reason is the complexity of the brain. So many different cells. So many different cell types. Another part of the reason is that the brain is hard to study. It is wrapped in our skull and is a large dense tissue. It is difficult for us to observe how this organization works. In addition, molecules and signals are so microscopic that these factors make studying the brain more challenging. So it made me understand that we need new technologies and tools to help break down different cells and different molecules to figure out how they work together in the brain system.

Sarah Zhang: How do you use CRISPR to study the brain?

Zhang Feng: Through DNA sequencing, scientists have discovered many genetic variations, some of which are related to increased risk of brain disease. Therefore, we used CRISPR to perform experiments on mice to try to understand how they work. What are the mechanisms that affect brain function?

Sarah Zhang: There are many patients who want to know how CRISPR can help them. Have you received their emails? ?

Zhang Feng: Yes, I receive emails from them every day. Patients and their relatives and friends are really trying to understand what this technology is. They want to know if there are ways to promote the development of this technology so that the corresponding treatment can be very effective. This is a very encouraging message. Every day I remind myself that it is possible to develop something that can really help people. As long as the work progress is accelerated, we can achieve our goal faster.

Sarah Zhang: Isn't this difficult? Because, as you said, there are still many challenges. You may have to tell some people that this is not possible in the short term.

Zhang Feng: I think we should remind everyone that we are fortunate enough to make positive changes. We should not mess it up.

Sarah Zhang: Who trusts CRISPR?

Zhang Feng: I think many people believe it. CRISPR is something that has been studied for decades, so there are many people involved in different stages of work. Some people are very important in early detection. Then other people pick up the baton and continue to study basic biology. This is the beauty of scientific discovery. Our results are based on previous research. This is how history or civilization was built and accumulated in bricks and mortar.

Sarah Zhang: Some of you scientists have started discussing the potential risks of using CRISPR technology in humans. Do you feel that you are in a position of moral authority, because it is you who help bring this technology into this world?

Zhang Feng: Then I think we all have the responsibility: scientists, media, policy makers, bioethics scientists are obliged to participate in this discussion. I think that as a scientist, we can help convey what technology is, help explain what it is, and understand what the potential of technology is.

One thing that made me very excited was how we turned CRISPR into a true therapeutic tool to cure those incurable diseases. One of the things that I'm very excited about is focusing on how to make CRISPR a true therapeutic tool so that we can treat diseases. We are still a long way from goals like making babies. We still don't know enough about biology. We didn't even think about what these things would be. We are not even able to cope with the single mutation that causes sickle cell disease. (晗冰)

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