Researchers use CRISPR to remove HIV from active genome for the first time

"Our research shows that successive treatments and gene-editing therapies that inhibit HIV replication can eliminate HIV from the cells and organs of infected animalsDrKamel Khalili said that he is Professor Laura HCarnell of LKSOM, Head of the Department of Neuroscience, Director of the Center for Neurovirology and Director of the Integrated NeuroAIDS CenterDrKhalili and DrHoward Gendelman, Professor of Infectious Diseases and UNMC Internal Medicine, Chair of the Department of Pharmacology and Experimental Neuroscience, and Director of the Center for Neurodegenerative Diseases, are the authors of the new studyPicture: Nature Communications
"This achievement would not have been possible without the joint efforts of virologists, immunologists, molecular biologists, pharmacologists and pharmacologists," DrGendelman saidOnly by pooling our resources can we make this breakthrough discovery"
current HIV treatment focuses on the use of antiretroviral therapy (ART)Antiretroviral therapy inhibits the replication of HIV, but does not eliminate the virus from the bodyTherefore, antiretroviral treatment does not cure HIV and requires lifelong useIf stopped, HIV would rebound, replicate and promote the development of AIDSThe rebound in HIV is directly due to the virus's ability to integrate its DNA sequenceinto into the immune system's cellular genome, where the virus is dormant and inaccessible to antiretroviral drugs previous work, Dr Khalili's team used CRISPR-Cas9 technology to develop a new gene editing and gene therapy delivery system designed to remove DNA from the HIV genome In rats and mice, they found that gene editing systems can effectively remove large amounts of HIV DNA fragments from infected cells, significantly affecting the expression of viral genes However, like ART, gene editing alone does not completely eliminate HIV in the in the new study, Dr Khalili and colleagues combined their gene editing system with a recently developed treatment strategy called long-acting slow release (laser) The laser technology was developed by Dr Gendelman and Dr Benson Edagwa, Assistant Professor of Pharmacology at UNMC laser antiretroviral therapy targets viral shelters and maintains low levels of HIV replication over an extended period of time, thereby reducing the frequency of antiretroviral treatment These long-acting drugs were introduced due to pharmacological changes in the chemical structure of antiretroviral drugs The modified drug is packaged into nanocrystals, which are easily distributed in tissues where HIV may be lurking From there, nanocrystals stored in cells for weeks slowly release the drug "We wanted to see if laser therapy could inhibit HIV replication for a long enough time to completely remove viral DNA from cells," said Dr Khalili to test their idea, the researchers used mice to create HIV-prone human T-cells, allowing long-term viral infections and ART-induced incubation periods Once the infection is determined, the mice receive laser treatment and are then treated with CRISPR-Cas9 At the end of the course, the mice were tested for viral load Analysis showed that about one-third of HIV-infected mice had completely disappeared from THEIR DNA "The main message of this work is that it needs CRISPR-Cas9 and laser ART to suppress the virus, while using methods such as laser ART to produce treatments for HIV infection," says Dr Khalili "We now have a clear path to trials in non-human primates within a year, or in human patients, " he said References: Howard E Gendelman et al Veer laser ART and CRISPR Treatments Eliminate HIV-1 in a Subset of Infected Humanized Mice, Nature Communications (2019) DOI: 10.1038/s41467-019-10366-y