艾滋病毒 z-bo 2020-09-18 449

　　Imagine using one drug to prevent human immunodeficiency virus (HIV) infection, treat patients already infected with HIV, and even remove all latent virus copies in patients with advanced disease. This sounds like science fiction, and scientists from the Salk Institute of Biology have developed a powerful defense system used by many bacteria and trained this scissor-like machine to recognize the HIV virus. The drug is a step closer.

　　Juan Carlos Izpisua Belmonte, senior author of the paper and professor at the Salk Institute of Biological Gene Expression Laboratory, said: "Evolution has led to some of the most surprising mechanisms to protect organisms from natural pathogens. Understanding how bacteria can protect themselves from viral infections With this immune response, we can design some new platforms to target some destructive viruses such as HIV in human patients."

　　When a copy of the HIV virus sneaks into human cells, it can cause huge damage. It diverts the cell's own molecular machinery into copies of the genetic material used to generate the virus, and then bury these copies in the cell's own genes. Since then, the host cell has become an HIV factory, generating new copies of the virus to spread throughout the body. Existing HIV drugs target individual steps in this life cycle; for example, some prevent the virus from integrating into the cell’s DNA, while others try to prevent the affected cells from producing more virus.

　　Hsin-Kai (Ken) Liao, the first author of the new paper and a research assistant in the Izpisua Belmonte laboratory, said: “These drugs have a problem: they cannot really remove the virus copies hidden in the cell’s DNA. These virus copies can be kept for many years. Sleep and then activate again."

　　Liao said: “Because HIV can be latent, patients usually need to take medication every day or every week for their lives. This consumes money, time and energy.”

　　To solve this problem, Liao and Izpisua Belmonte turned to a molecular defense system called CRISPR, which bacteria use to cut foreign DNA at specific sites. Since its discovery in recent years, scientists have begun to use CRISPR to edit some genes. Liao and Izpisua Belmonte were also attracted by its defense capabilities, wondering if CRISPR could be programmed to cut and destroy viruses in human cells.

　　CRISPR uses fragments of genetic material called guide RNAs (gRNAs) to guide cutting, so scientists have developed some guide RNAs that bind to unique sites on the HIV virus. In order to allow this system to work on HIV-infected immune cells, they added CRISPR, guide RNAs, and other required molecules, and found that CRISPR successfully cut the correct site of the HIV gene and inactivated the virus. This makes up to 72% of the cells completely cleared of the virus. CRISPR not only cuts off the released copies of the virus when the virus starts to infect the cell, but also shreds the HIV hidden in the cell's DNA.

　　Although some other research groups have reported that similar methods are used to target HIV with CRISPR, new research from the Salk Institute of Biology has confirmed that this method is effective against activated, full-length HIV rather than shortened, inactivated HIV. Version of the virus. The research team also clarified in a more complete way how CRISPR targets HIV in living human cells, confirming that it can play a role before and after the virus is inserted into the genome.

　　Liao said: "CRISPR can really remove this virus from the human genome."

　　Next, Liao and his colleagues tried to add the CRISPR system to human cells before HIV infection. They confirmed that this system can prevent HIV infection-CRISPR chopped up all copies of the virus before HIV began to replicate.

　　Izpisua Belmonte said: "The main advantage of this technology is not only that it can remove viral DNA integrated into the human genome, but most importantly, its preventive application. By eliminating it in the early stages of the virus life cycle, we can be similar to conventional vaccines. Way of action to prevent human cell infection."

　　However, more research is still needed to determine how to use this technology in human patients and whether HIV will evolve rapidly to avoid CRISPR. With this in mind, the research team is studying the effectiveness of adding more guide RNAs to the CRISPR mix to enable this defense to recognize more areas of the virus at the same time. Liao said: "The HIV virus can mutate extremely quickly. If we target multiple areas at the same time, we can reduce the chance of the virus developing resistance."