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Sequential LASER ART and CRISPR Treatments Eliminate HIV-1 in a Subset of Infected Humanized Mice
Dash, PK Kaminski, R Bella, R Su, H Mathews, S Ahooyi, TM Chen, C Mancuso, P Sariyer, R Ferrante, P
Dash, PK
Kaminski, R
Bella, R
Su, H
Mathews, S
Ahooyi, TM
Chen, C
Mancuso, P
Sariyer, R
Ferrante, P
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Journal Article
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2019-12-01
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10.1038/s41467-019-10366-y
Abstract
© 2019, The Author(s). 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.
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