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Sequential LASER ART and CRISPR Treatments Eliminate HIV-1 in a Subset of Infected Humanized Mice

Author

Listed:
  • Prasanta K. Dash

    (University of Nebraska Medical Center)

  • Rafal Kaminski

    (Lewis Katz School of Medicine at Temple University)

  • Ramona Bella

    (Lewis Katz School of Medicine at Temple University)

  • Hang Su

    (University of Nebraska Medical Center)

  • Saumi Mathews

    (University of Nebraska Medical Center)

  • Taha M. Ahooyi

    (Lewis Katz School of Medicine at Temple University)

  • Chen Chen

    (Lewis Katz School of Medicine at Temple University)

  • Pietro Mancuso

    (Lewis Katz School of Medicine at Temple University)

  • Rahsan Sariyer

    (Lewis Katz School of Medicine at Temple University)

  • Pasquale Ferrante

    (Lewis Katz School of Medicine at Temple University)

  • Martina Donadoni

    (Lewis Katz School of Medicine at Temple University)

  • Jake A. Robinson

    (Lewis Katz School of Medicine at Temple University)

  • Brady Sillman

    (University of Nebraska Medical Center)

  • Zhiyi Lin

    (University of Nebraska Medical Center)

  • James R. Hilaire

    (University of Nebraska Medical Center)

  • Mary Banoub

    (University of Nebraska Medical Center)

  • Monalisha Elango

    (University of Nebraska Medical Center)

  • Nagsen Gautam

    (College of Pharmacy, University of Nebraska Medical Center)

  • R. Lee Mosley

    (University of Nebraska Medical Center)

  • Larisa Y. Poluektova

    (University of Nebraska Medical Center)

  • JoEllyn McMillan

    (University of Nebraska Medical Center)

  • Aditya N. Bade

    (University of Nebraska Medical Center)

  • Santhi Gorantla

    (University of Nebraska Medical Center)

  • Ilker K. Sariyer

    (Lewis Katz School of Medicine at Temple University)

  • Tricia H. Burdo

    (Lewis Katz School of Medicine at Temple University)

  • Won-Bin Young

    (Lewis Katz School of Medicine at Temple University)

  • Shohreh Amini

    (Lewis Katz School of Medicine at Temple University)

  • Jennifer Gordon

    (Lewis Katz School of Medicine at Temple University)

  • Jeffrey M. Jacobson

    (Lewis Katz School of Medicine at Temple University)

  • Benson Edagwa

    (University of Nebraska Medical Center)

  • Kamel Khalili

    (Lewis Katz School of Medicine at Temple University)

  • Howard E. Gendelman

    (University of Nebraska Medical Center)

Abstract

Elimination of HIV-1 requires clearance and removal 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.

Suggested Citation

  • 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 & Br, 2019. "Sequential LASER ART and CRISPR Treatments Eliminate HIV-1 in a Subset of Infected Humanized Mice," Nature Communications, Nature, vol. 10(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10366-y
    DOI: 10.1038/s41467-019-10366-y
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