Treating HIV-infected mice with a combination therapy that includes CRISPR .

Title: Sequential LASER ART and CRISPR Treatments Eliminate HIV-1 in a Subset of Infected Humanized Mice
Journal:
Prasanta K. Dash, Rafal Kaminski, Ramona Bella, Hang Su, Saumi Mathews, Taha M. Ahooyi, Chen Chen, Pietro Mancuso, Rahsan Sariyer, Pasquale Ferrante, Martina Donadoni, Jake A. Robinson, Brady Sillman, Zhiyi Lin, James R. Hilai, Mary Bana, MonaliSha Gautam, R. Lee Mosley, Larisa Y. Poluektova, Jo Ellyn McMillan, Aditya N. Bade, Santhi Gorantla, Ilker K. Sariyer, Tricia H. Burdo, Won-Bin Young, Shohreh Amini, Jennifer Gordon, Jeffrey M. Jacobson, Benson Edgwa, Kamel Khalili, Howard E. Gendelman
Published: 2019/07/02
Digital Identification Number: 10.1038/s41467-019-10366-y
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A study published in Nature-Newsletter
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A total of 13 mice were treated in two separate trials, five of which showed no signs of HIV infection for up to five weeks after treatment. In contrast, HIV was easily detected in mice that received one of the treatments alone.
, HIV-infected patients rely mainly on a variety of antiviral drugs for treatment. However, this treatment does not cure the patient and requires lifelong medication.Howard Gendelman of the University of Nebraska Medical Center in the United States, Kamel Khalili of the Lewis Katz School of Medicine at Temple University in the United States, and colleagues developed a combination therapy for HIV, targeting HIV in a group of infected mice. The treatment relies on an antiviral drug formulation and CRISPR-Cas9 technology, which slowly releases the drug for days and inhibits viral activity, and CRISPR, which eliminates the viral genetic code in infected cells by cutting off the relevant DNA fragments.
although the results in mice are promising, the authors plan to conduct further studies to improve drug delivery in viral storage and specifically eliminate latent viral infections.
summary: End of HIV-1 requires clearance and removal of of integrated proviral DNA from infected cells and tissues. Here, sequential long-acting slow-effective release antiviral therapy (LASER ART) and CRISPR-Cas9 demonstrate viral clearance in latent infectious reservoirs in HIV-1 infected humanized mice. HIV-1 subgenomic DNA fragments, spanning the long terminal repeats and the Gag gene, are excised in vivo, resulting in elimination of integrated proviral DNA; virus is not detected in blood, lymphoid tissue, bone marrow and brain by nested and digital-droplet PCR as well as RNAscope tests. No CRISPR-Cas9 mediated off-target effects are detected. Adoptive transfer of human immunocytes from dual treated, virus-free animals to uninfected humanized mice fails to produce infectious progeny virus. In contrast, HIV-1 is readily detected following sole LASER ART or CRISPR-Cas9 treatment. These data provide proof-of-concept that permanent viral elimination is possible.
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(Source: Science.com)