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Sequential LASER ART and CRISPR Treatments Eliminate HIV-1 in a Subset of Infected Humanized Mice.
Dash, Prasanta K; Kaminski, Rafal; Bella, Ramona; Su, Hang; Mathews, Saumi; Ahooyi, Taha M; Chen, Chen; Mancuso, Pietro; Sariyer, Rahsan; Ferrante, Pasquale; Donadoni, Martina; Robinson, Jake A; Sillman, Brady; Lin, Zhiyi; Hilaire, James R; Banoub, Mary; Elango, Monalisha; Gautam, Nagsen; Mosley, R Lee; Poluektova, Larisa Y; McMillan, JoEllyn; Bade, Aditya N; Gorantla, Santhi; Sariyer, Ilker K; Burdo, Tricia H; Young, Won-Bin; Amini, Shohreh; Gordon, Jennifer; Jacobson, Jeffrey M; Edagwa, Benson; Khalili, Kamel; Gendelman, Howard E.
Afiliação
  • Dash PK; Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA.
  • Kaminski R; Department of Neuroscience, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19115, USA.
  • Bella R; Department of Neuroscience, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19115, USA.
  • Su H; Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA.
  • Mathews S; Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA.
  • Ahooyi TM; Department of Neuroscience, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19115, USA.
  • Chen C; Department of Neuroscience, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19115, USA.
  • Mancuso P; Department of Neuroscience, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19115, USA.
  • Sariyer R; Department of Neuroscience, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19115, USA.
  • Ferrante P; Department of Neuroscience, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19115, USA.
  • Donadoni M; Department of Neuroscience, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19115, USA.
  • Robinson JA; Department of Neuroscience, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19115, USA.
  • Sillman B; Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA.
  • Lin Z; Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA.
  • Hilaire JR; Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA.
  • Banoub M; Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA.
  • Elango M; Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA.
  • Gautam N; Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA.
  • Mosley RL; Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA.
  • Poluektova LY; Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA.
  • McMillan J; Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA.
  • Bade AN; Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA.
  • Gorantla S; Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA.
  • Sariyer IK; Department of Neuroscience, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19115, USA.
  • Burdo TH; Department of Neuroscience, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19115, USA.
  • Young WB; Department of Neuroscience, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19115, USA.
  • Amini S; Department of Neuroscience, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19115, USA.
  • Gordon J; Department of Neuroscience, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19115, USA.
  • Jacobson JM; Department of Neuroscience, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19115, USA.
  • Edagwa B; Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA.
  • Khalili K; Department of Neuroscience, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19115, USA. kamel.khalili@temple.edu.
  • Gendelman HE; Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA. hegendel@unmc.edu.
Nat Commun ; 10(1): 2753, 2019 07 02.
Article em En | MEDLINE | ID: mdl-31266936
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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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Infecções por HIV / HIV-1 / Fármacos Anti-HIV / Sistemas CRISPR-Cas Limite: Animals / Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Reino Unido
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Infecções por HIV / HIV-1 / Fármacos Anti-HIV / Sistemas CRISPR-Cas Limite: Animals / Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Reino Unido