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.

Sequential LASER ART and CRISPR treatments eliminate HIV-1 in a subset of infected humanized mice / P.K. Dash, R. Kaminski, R. Bella, H. Su, S. Mathews, T.M. Ahooyi, C. Chen, P. Mancuso, R. Sariyer, P. Ferrante, M. Donadoni, J.A. Robinson, B. Sillman, Z. Lin, J.R. Hilaire, M. Banoub, M. Elango, N. Gautam, R.L. Mosley, L.Y. Poluektova, J.E. McMillan, A.N. Bade, S. Gorantla, I.K. Sariyer, T.H. Burdo, W.B. Young, S. Amini, J. Gordon, J.M. Jacobson, B. Edagwa, K. Khalili, H.E. Gendelman. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 10(2019 Jul 02), pp. 2753.1-2753.20.

Sequential LASER ART and CRISPR treatments eliminate HIV-1 in a subset of infected humanized mice

Bella R.;Ferrante P.;Donadoni M.;
2019-07-02

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.
Settore MED/07 - Microbiologia e Microbiologia Clinica
NATURE COMMUNICATIONS
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/659564
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