@article{0fed7b51dfa94a759ed68b143ead9bed,
title = "Sequential LASER ART and CRISPR Treatments Eliminate HIV-1 in a Subset of Infected Humanized Mice",
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.",
author = "Dash, {Prasanta K.} and Rafal Kaminski and Ramona Bella and Hang Su and Saumi Mathews and Ahooyi, {Taha M.} and Chen Chen and Pietro Mancuso and Rahsan Sariyer and Pasquale Ferrante and Martina Donadoni and Robinson, {Jake A.} and Brady Sillman and Zhiyi Lin and Hilaire, {James R.} and Mary Banoub and Monalisha Elango and Nagsen Gautam and Mosley, {R. Lee} and Poluektova, {Larisa Y.} and McMillan, {Jo Ellyn} and Bade, {Aditya N.} and Santhi Gorantla and Sariyer, {Ilker K.} and Burdo, {Tricia H.} and Young, {Won Bin} and Shohreh Amini and Jennifer Gordon and Jacobson, {Jeffrey M.} and Benson Edagwa and Kamel Khalili and Gendelman, {Howard E.}",
note = "Funding Information: We greatly appreciate past and present members of the Center for Neurovirology and the Department of Neuroscience at the Lewis Katz School of Medicine at Temple University and the Center for Neurodegenerative Diseases and Department of Pharmacology and Experimental Neuroscience and Pharmaceutical Sciences, University of Nebraska Medical Center. These members include Drs. Martyn White (deceased), Tracy Fischer, Wenhui Hu, Siddappa Byrareddy, Shilpa Buch, Howard S. Fox and Yazen Alnouti for intellectual exchanges. We want to thank Midhun Ben Thomas, Divyaprakash Gnanadhas, Weimen Wang, Yan Cheng, Sruthi Sravanam for technical assistance. We wish to thank Ms. Cindy Papaleo and Robin Taylor for assistance in formatting and editing the manuscript. A thank you is extended to Dr. Carl V. Smith, the nursing and attending physicians in the Department of Obstetrics and Gynecology University of Nebraska Medical Center for cord blood sample acquisitions used for the mouse humanizations. This work was supported by ViiV Healthcare, the University of Nebraska Foundation, the Carol Swarts, M.D. Emerging Neuroscience Research Laboratory, the Margaret R. Larson Professorship, the Frances and Louie Blumkin and Harriet Singer Endowments and by the National Institute of Health grants awarded to Temple University and University of Nebraska Medical Center including R01MH104147, R01NS36126, R01NS034239, P01NS43985, P30MH062261, P30AI078498, R01AG043540, P30MH092177, P01DA028555, P01DA037830, R01MH110360, R01DA013137, R01NS087971, R24OD018546 and R01DA42706. Publisher Copyright: {\textcopyright} 2019, The Author(s).",
year = "2019",
month = dec,
day = "1",
doi = "10.1038/s41467-019-10366-y",
language = "English (US)",
volume = "10",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}