UNMC, LKSOM Researchers Successfully Remove HIV from Animal in Major Medical Discovery
July 2, 2019
OMAHA, Nebraska - In a major collaborative effort, researchers at the University of Nebraska Medical Center and the Lewis Katz School of Medicine at Temple University have, for the first time, eliminated replication-competent HIV-1 DNA- the virus responsible for AIDS- from the genomes of living animals.
The study, reported online July 2 in the journal Nature Communications, marks a critical step toward the development of a possible cure for human HIV infection.
"This achievement could not have been possible without an extraordinary team effort that included virologists, immunologists, molecular biologists, pharmacologists, and pharmaceutical experts," said Howard Gendelman, M.D., Margaret R. Larson Professor of Infectious Diseases and Internal Medicine, chair of the Department of Pharmacology and Experimental Neuroscience and director of the Center for Neurodegenerative Diseases at UNMC. "Only by pooling our resources together were we able to make this groundbreaking discovery."
"Our study shows that treatment to suppress HIV replication and gene editing therapy, when given sequentially, can eliminate HIV from cells and organs of infected animals," said Kamel Khalili, Ph.D., Laura H. Carnell Professor and chair of the Department of Neuroscience, director of the Centerfor Neurovirology, and director of the Comprehensive NeuroAIDS Center at LKSOM.
Drs. Gendelman and Khalili were senior investigators on the new study.
Current HIV treatment centers on the use of antiretroviral therapy. ART suppresses HIV
replication but does not eliminate the virus from the body. Therefore, ART is not a cure for HIV, and it requires lifelong use. If it is stopped, HIV rebounds, renewing replication and fueling the development of AIDS. (...)
For the present study, Gendelman and his team led by Prasanta Dash, Ph.D., instruction of pharmacology, combined its Lasert Art strategy with the gene editing system.
The method targets viral sanctuaries and maintains HIV replication at low levels for extended periods of time, reducing the frequency of ART administration.
The long-lasting medications were made possible by pharmacological changes in the chemical structure of the antiretroviral drugs.
The modified drug was packaged into nanocrystals, which readily distribute to tissues where HIV is likely to be lying dormant. From there, the nanocrystals, stored within cells for weeks, slowly release the drug.
Khalili said, "We wanted to see whether LASER ART could suppress HIV replication long enough for CRISPR-Cas9 to completely rid cells of viral DNA."
To test their idea, the researchers used mice engineered to produce human T cells susceptible to HIV infection, permitting long-term viral infection and ART-induced latency.
Once the infection was established, mice were treated with LASER ART and subsequently with CRISPR-Cas9. At the end of the treatment period, mice were examined for viral load.
Analyses revealed complete elimination of HIV DNA in about one-third of HIV-infected mice.
"The ability to excise HIV-1 DNA from the genomes of infected animals depends on LASER ART's abilities to maximally restrict ongoing infection. This concept of combining both modalities provides a pathway forward to future studies in humans," Dr. Gendelman said.
Article submitted by John Schneiderwind
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