HIV is an efficient and variable retrovirus. When the virus inserts its DNA into the genome of the host cell, it has a longer incubation period and can hide in a dormant state for several years. Doctors can use a variety of antiretroviral drugs to control the virus, but they can restore the virus by stopping treatment. In order to inactivate the potential HIV virus, researchers at the University of Massachusetts Medical School (University of Massachusetts Medical School) are developing a powerful gene editing system that can prevent Cas9/release of viral DNA from infected cells. New technology using CRISPR.
"In short, you can precisely remove all or part of the HIV genome and reconnect the broken ends of the human genome," said Dr. Scott Wolf, co-research director at the University of Massachusetts. He said he is an associate professor of molecular biology, cell biology and tumor biology at the medical school. "If it can be done, this will be an important step in the process of AIDS functional treatment."
CRISPR sequence is an immune component found in normal bacteria, which can protect them from viruses in their natural state. were able. Since its discovery, researchers have been actively studying ways to use the system to quickly and selectively edit specific gene sequences.
Despite its wide range of uses, the application of CRISPR sequencing is still limited to the laboratory. Research progress has shown that Cas9/CRISPR can edit HIV-related genes in cultured infected cells, but this technology is not accurate enough for clinical applications. The location where the genome is cut is often random, which often produces harmful non-target effects.
Cas9 / In order to improve the accuracy and accuracy of CRISPR and meet the requirements of the project, Wolf recommends integrating it with other technologies to improve the specificity of the method. It can accurately edit HIV DNA without accidentally cutting the human genome with CRISPR sequences.
There is another obstacle to using Cas9/CRISPR to fight AIDS. Researchers may know where the virus is lurking, but they still don’t know how to find him in the cells where the virus is lurking.
" Partner and MD Jeremy said: "The cells infected with HIV will always carry the viral genome. They are like time bombs. If patients stop antiretroviral therapy, they can always resume activities. Luban said. He is a memorial professor of David J. Freelander and a professor of molecular medicine at the Center for AIDS Research at the University of Massachusetts Medical School. "To attack a latent virus, we need to understand the location of the virus and the conditions under which it survives."
Luban and Wolfe use a variety of new technologies. The HIV DNA that records and synthesizes the ability to integrate into host cells is also called a provirus. Describing the genetic characteristics of these potentially infected cells can identify sensitive and easily accessible gene sequences that allow researchers to remove some HIV genes and inactivate the HIV virus for a long time. beneficial to.
Luban said: "Many scientists are looking for ways to activate the virus and expose it to the immune system and drugs, but we chose another method to isolate and remove the original virus directly from dormant cells."
A genetic template that potentially infects cells enables Wolff to use its genetic coding system to remove viruses from cells. Part of the feasibility of the project is humanized mice. This depends on whether the HIV gene resection system of the model can achieve sufficient accuracy, and whether the system also destroys the human genome of the infected patient's cells.
"While the new technology developed by Wolff promotes the project, the basic premise of the project is to use genetic engineering to design a system that can remove HIV genes from infected cells," Luban said. The medicine can directly reach the human immune system and eliminate hidden dangers. "
Wolfe said: "We have established a research team at the University of Massachusetts to better understand the potential HIV integrated into immune cells, which allows us to better use CRISPR technology to target HIV through gene editing. I Believe. "