Sequential LASER ART and CRISPR Treatments Eliminate HIV-1 in a Subset of Infected Humanized Mice
Genre
Journal ArticleDate
2019-12-01Author
Dash, PKKaminski, R
Bella, R
Su, H
Mathews, S
Ahooyi, TM
Chen, C
Mancuso, P
Sariyer, R
Ferrante, P
Donadoni, M
Robinson, JA
Sillman, B
Lin, Z
Hilaire, JR
Banoub, M
Elango, M
Gautam, N
Mosley, RL
Poluektova, LY
McMillan, JE
Bade, AN
Gorantla, S
Sariyer, IK
Burdo, TH
Young, WB
Amini, S
Gordon, J
Jacobson, JM
Edagwa, B
Khalili, K
Gendelman, HE
Subject
Adoptive TransferAnimals
Anti-HIV Agents
CRISPR-Cas Systems
Combined Modality Therapy
DNA, Viral
Gene Editing
HIV Infections
HIV-1
Humans
Mice
Treatment Outcome
Virus Latency
Permanent link to this record
http://hdl.handle.net/20.500.12613/4315
Metadata
Show full item recordDOI
10.1038/s41467-019-10366-yAbstract
© 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.Citation to related work
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http://dx.doi.org/10.34944/dspace/4297