CRISPR, combined with new antiretroviral therapy, heals HIV in mice for the first time – Technology News, Firstpost

Tech2 News Staff08 Jul 2019 15:08:02 IST

Scientists from Temple University and the Medical Center of the University of Nebraska have successfully removed DNA from the Human Immunodeficiency Virus (HIV) causing AIDS, entirely in the genome of a living animal. This remarkable first in medicine was made possible by a vast project of collaboration between the two universities.

The treatment used in the study suppresses HIV replication, followed by a gene editing treatment cycle. When administered sequentially, this combination therapy eliminated HIV from infected animal cells and organs.

Dr. Kamel Khalili, director of the Neurovirology Center at Temple University and Howard Gendelman, director of the Center for Neurodegenerative Diseases of the UNMC, were the principal investigators of the study. "This success would not have been possible without an extraordinary team effort including virologists, immunologists, molecular biologists, pharmacologists and pharmaceutical experts," Gendelman said. A declaration. "Only by pooling our resources could we make this revolutionary discovery."

HIV virus, in green, attaching to a white blood cell, in orange, as seen in a colored transmission electron microscope. Image credit: NIBSC

At present, HIV treatment is focused on the use of antiretroviral therapy (ART). Antiretroviral therapy suppresses replication of HIV at levels that make it undetectable in a person's blood. But antiretroviral therapy alone can not eliminate the virus from the body, that is, it is not a cure for HIV, but a treatment that must be used for life. If HIV is stopped, HIV bounces back and continues to replicate in the body, fueling the development of AIDS over months and years.

For HIV to rebound after being removed by antiretroviral therapy, the DNA of the virus must be integrated with the genetic material stored in the cells of the immune system. It is there that HIV is dormant and out of reach of antiretrovirals for years.

Dr. Khalili's team used CRISPR-Cas9 technology to develop a novel gene therapy editing and therapy system that removes HIV DNA from the human genomes that house it, reporting their findings in a timely manner. previous study. Using rats and mice as subjects, gene editing has been used successfully to cut large pieces of HIV DNA into infected cells. That said, just like antiretroviral therapy, gene editing alone can not eliminate HIV from an infected person.

In a new study, researchers have linked their gene editing system to a new strategy called long-acting slow release (LASER) slow-release (LASER), developed jointly by two pharmacology researchers, Dr. Gendelman and Dr. Gendelman. Benson Edagwa of the UNMC.

LASER ART, unlike conventional antiretroviral therapy, exclusively targets virus sanctuaries and maintains HIV replication at undetectable levels in the blood for longer, reducing the need to treat a patient frequently with antiretroviral therapy. This long-lasting drug was created by tweaking the chemical structure of the antiretroviral drug, conditioning it into nanocrystals. These nanocrystals are easily distributed in the tissues most likely to contain dormant HIV sanctuaries. The nanocrystals are stored in cells for weeks, triggering a slow and prolonged action of antiretroviral therapy where it really matters.

"We wanted to know if LASER laser therapy could suppress HIV replication long enough for CRISPR-Cas9 to completely eliminate viral DNA cells," Dr. Khalili said. the statement.

Testing their LASER-ART theory, the researchers used mice likely to produce HIV-sensitive immune cells, to harbor the long-term viral infection and mimic the state of dormancy. dependent on ART in HIV patients. Once infected, the mice were treated with LASER ART, then CRISPR-Cas9. At the end of the treatment period, the viral load of the mice was examined, which showed the complete elimination of HIV DNA in 33% of seropositive mice.

This new development is the biggest advance in HIV medicine since LASER ART itself.

Research and its discoveries, reported in Nature Communications on July 2, marks a crucial step towards the development of a possible cure for HIV infection by humans.

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