乙型肝炎 z-bo 2020-09-23 372

　　The "RNA" silencing method comes from a company derived from the University of Wisconsin-Madison. This method that can resist hepatitis B infection and avoid liver damage is undergoing clinical trials in Europe, Asia and the United States.

　　Use RNA interference technology to silence the expression of a specific RNA so that the disease caused by this gene will not be activated. In theory, this technology can cure viral or genetic diseases.

　　The silent technology being used by Arrow Pharmaceuticals was invented by Mirusbio, which was derived from the pediatric laboratory of Jon Wolff at the University of Wisconsin-Madison. The technology authorized by the Wisconsin Alumni Research Foundation has proven to be an effective application technology.

　　Hepatitis B can be prevented by injecting hepatitis B vaccine. Even for those who have not been vaccinated, the human immune system usually clears the infection. David Lewis, the chief research officer of Arrow Medical Research Institute at Madison, said: "But in 10% of cases, the hepatitis B virus can secrete a protein that suppresses the immune response, leading to chronic infection."

　　Arrow Pharmaceuticals is a private stock. On the one hand, its issuance aims to raise US$45 million for the development of hepatitis B drugs, and on the other hand, it aims to treat the so-called "α-1 antitrypsin deficiency" A rare inherited liver and lung disease.

　　There are approximately 340 million people with chronic hepatitis B infection in the world, including 2 million in the United States. Chronic hepatitis B infection may cause liver cancer or the loss of basic liver metabolism.

　　The research facility at Madison is affiliated with Arrow Pharmaceuticals in Passatini, California. Lewis said: "Our strategy is to use RNA silencing technology to reduce the production of viral proteins that weaken the immune system, so that the immune system can recover to the extent that it can clear the virus, just like the other 90% who are infected with hepatitis B but have not developed chronic infections. The immune system in the human body is the same."

　　RNA guides DNA synthesis. RNA interference technology was discovered in 1998. At that time, it was like a magic bullet. It could specifically kill off the problem genes to fight diseases. Such a vision is difficult to achieve. RNAi drugs that have not been approved by the FDA have entered the market, although two such drugs are in the late stages of clinical trials.

　　Generally speaking, the short-stranded RNA used in RNA interference technology is designed to destroy unnecessary RNA or prevent it from producing protein. The process of shearing messenger RNA through RNA interference technology is a "natural process". Lewis said: "Almost all cells have this ability. This is another level of gene expression regulation." In gene expression, DNA is transcribed into RNA and RNA is translated into protein.

　　In the early stages of the development of RNA interference technology, short-stranded RNA injected into the human body is often excreted from the body through urine and cannot produce beneficial effects. The result is "very expensive urine," Lewis said.

　　But at Mirus, Lewis and other researchers invented a system that connects short strands of RNA with a molecule that can identify and lock liver cells. At least in liver disease, this door seems to be open to finding a way to RNA interference.

　　RNA interference technology is so attractive that in 2008 the pharmaceutical giant Hoffmann-La Roche acquired Mirus's RNA interference technology research department, even though it has left the laboratory at Madison. But within three years, Roche changed his mind and sold the business to Arrow Company, just as he abandoned the research and development of jamming technology at Madison. Arrow Pharmaceuticals currently employs 90 researchers in the University Research Park and Middleton.

　　While working in Sean Carroll's lab, Lewis learned about RNA interference technology. Sean Carroll is a genetics expert at the University of Wisconsin-Madison. He studies the gene regulation that gives animals a specific body structure. Lewis said: "Sean wants to know how the genes that control butterfly wing traits produce different patterns, so he wants to manipulate where the genes are expressed." For his postdoctoral project, "I hope these genes are expressed in the wrong place, or apply RNA interference technology silences these genes to observe their effects."

　　Lewis, a Mirus company, devoted himself to the research of hepatocyte targeting technology. He first acquired Roche as the company and then went to Arrow Pharmaceuticals.

　　The company is also developing other RNAi drugs, including some for cardiovascular diseases, but its main job is to conduct the phase 2 (dose level) study of hepatitis B clinical trials. Lewis said, this is a difficult task. Task. "Each country has its own regulatory requirements for clinical trials, so to apply for the right to use all these drugs in more than 12 countries will require tremendous efforts."

　　Lewis said: Different doses of hepatitis drugs are being tested, sometimes in combination with other antiviral drugs.

　　"The drug itself will not clear the virus," he emphasized. "This is the job of the immune system. Even if they still have viral DNA hidden somewhere, the current immune system can recognize the cells that produce viral antigens and destroy it."