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Ripping HIV out of the genome
07-09-2019
by Jeffrey Bouley  |  Email the author
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PHILADELPHIA—One of the biggest problems with HIV/AIDS has been that no matter how much treatments have improved to make it less a death sentence and more a major chronic illness, a cure has remained elusive. But perhaps CRISPR gene editing can change that, based on work coming out of the Lewis Katz School of Medicine at Temple University and the University of Nebraska Medical Center (UNMC).
 
On July 2, news emerged that Katz and UNMC researchers have for the first time reportedly eliminated replication-competent HIV-1 DNA—the virus responsible for AIDS—from the genomes of living animals.
 
The study, reported in the journal Nature Communications, marks what Excision BioTherapeutics calls “a critical step toward the development of a possible cure for human HIV infection.” Excision holds the exclusive license for any commercial application that come out of the technological advancements the researchers were employing. In general, the company is working on the development and commercialization of advanced gene-editing therapies for life-threatening viral diseases.
 
“We are incredibly proud of the medical breakthroughs made by this team of scientists. As the exclusive license holders from Temple on the technology and patents behind these innovations, Excision is working closely with the team to bring these advances to human clinical trials and to patients in need around the world,” said Daniel Dornbusch, CEO of Excisio.
 
The results of the study validate the use of a novel approach to using the powerful CRISPR-Cas9 gene editing and gene therapy platform in order to remove HIV DNA from genomes harboring the virus. Using the proprietary approach to CRISPR-Cas9 gene editing, HIV-infected mice were able to be removed from antiretroviral therapy without viral rebound from previously-infected cells.
 
“The results further validate the efforts of Excision to take the product forward to patients, and it’s one of the primary reasons I became a founding member of the company,” remarked Dr. Kamel Khalili chair of the Neuroscience Department at the Katz School of Medicine and founder and principal scientific advisor to Excision BioTherapeutics. “The next step is to bring this from the bench to the clinic, and to make this life-changing development commercially available.”
 
And, to that end, the company is looking to enter into clinical trials with its HIV-1 targeted CRISPR platform.
 
For the new study, Khalili and colleagues combined their gene-editing system with long-acting slow-effective release (LASER) ART, co-developed by Dr. Howard Gendelman, the Margaret R. Larson Professor of Internal Medicine and Infectious Diseases as well as chair of the Department of Pharmacology and Experimental Neuroscience at UNMC and Dr. Benson Edagwa, an assistant professor of pharmacology at UNMC. LASER ART packages HIV antiretroviral drugs into nanocrystals which reduces the frequency of ART administration and enables more effective HIV studies in animal models.
 
As Gendleman noted in an interview with NET (Nebraska’s public radio/television stations), one of the key achievements in their animal research they conducted that they made was to transform antiretroviral drugs from a water-soluble, short half-life medicine “to a nanocrystal and encased it into a nanoformulation that can be given infrequently and is long-lasting over a period of months up to as long as a year.”
 
Code: E07101903

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