Sequential LASER ART and CRISPR Treatments Eliminate HIV-1 in a Subset of Infected Humanized Mice
Identifieur interne : 000436 ( Main/Exploration ); précédent : 000435; suivant : 000437Sequential LASER ART and CRISPR Treatments Eliminate HIV-1 in a Subset of Infected Humanized Mice
Auteurs : Prasanta K. Dash [États-Unis] ; Rafal Kaminski [États-Unis] ; Ramona Bella [États-Unis] ; Hang Su [États-Unis] ; Saumi Mathews [États-Unis] ; Taha M. Ahooyi [États-Unis] ; Chen Chen [États-Unis] ; Pietro Mancuso [États-Unis] ; Rahsan Sariyer [États-Unis] ; Pasquale Ferrante [États-Unis] ; Martina Donadoni [États-Unis] ; Jake A. Robinson [États-Unis] ; Brady Sillman [États-Unis] ; Zhiyi Lin [États-Unis] ; James R. Hilaire [États-Unis] ; Mary Banoub [États-Unis] ; Monalisha Elango [États-Unis] ; Nagsen Gautam [États-Unis] ; R. Lee Mosley [États-Unis] ; Larisa Y. Poluektova [États-Unis] ; Joellyn Mcmillan [États-Unis] ; Aditya N. Bade [États-Unis] ; Santhi Gorantla [États-Unis] ; Ilker K. Sariyer [États-Unis] ; Tricia H. Burdo [États-Unis] ; Won-Bin Young [États-Unis] ; Shohreh Amini [États-Unis] ; Jennifer Gordon [États-Unis] ; Jeffrey M. Jacobson [États-Unis] ; Benson Edagwa [États-Unis] ; Kamel Khalili [États-Unis] ; Howard E. Gendelman [États-Unis]Source :
- Nature Communications [ 2041-1723 ] ; 2019.
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.
Url:
DOI: 10.1038/s41467-019-10366-y
PubMed: 31266936
PubMed Central: 6606613
Affiliations:
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Poluektova</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0666 4105</institution-id><institution-id institution-id-type="GRID">grid.266813.8</institution-id><institution>Department of Pharmacology and Experimental Neuroscience,</institution><institution>University of Nebraska Medical Center,</institution></institution-wrap>Omaha, NE 68198-5880 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Nebraska</region></placeName><wicri:cityArea>Omaha</wicri:cityArea></affiliation></author><author><name sortKey="Mcmillan, Joellyn" sort="Mcmillan, Joellyn" uniqKey="Mcmillan J" first="Joellyn" last="Mcmillan">Joellyn Mcmillan</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0666 4105</institution-id><institution-id institution-id-type="GRID">grid.266813.8</institution-id><institution>Department of Pharmacology and Experimental Neuroscience,</institution><institution>University of Nebraska Medical Center,</institution></institution-wrap>Omaha, NE 68198-5880 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Nebraska</region></placeName><wicri:cityArea>Omaha</wicri:cityArea></affiliation></author><author><name sortKey="Bade, Aditya N" sort="Bade, Aditya N" uniqKey="Bade A" first="Aditya N." last="Bade">Aditya N. Bade</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0666 4105</institution-id><institution-id institution-id-type="GRID">grid.266813.8</institution-id><institution>Department of Pharmacology and Experimental Neuroscience,</institution><institution>University of Nebraska Medical Center,</institution></institution-wrap>Omaha, NE 68198-5880 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Nebraska</region></placeName><wicri:cityArea>Omaha</wicri:cityArea></affiliation></author><author><name sortKey="Gorantla, Santhi" sort="Gorantla, Santhi" uniqKey="Gorantla S" first="Santhi" last="Gorantla">Santhi Gorantla</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0666 4105</institution-id><institution-id institution-id-type="GRID">grid.266813.8</institution-id><institution>Department of Pharmacology and Experimental Neuroscience,</institution><institution>University of Nebraska Medical Center,</institution></institution-wrap>Omaha, NE 68198-5880 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Nebraska</region></placeName><wicri:cityArea>Omaha</wicri:cityArea></affiliation></author><author><name sortKey="Sariyer, Ilker K" sort="Sariyer, Ilker K" uniqKey="Sariyer I" first="Ilker K." last="Sariyer">Ilker K. 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Jacobson</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2248 3398</institution-id><institution-id institution-id-type="GRID">grid.264727.2</institution-id><institution>Department of Neuroscience,</institution><institution>Lewis Katz School of Medicine at Temple University,</institution></institution-wrap>Philadelphia, PA 19115 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Philadelphia</wicri:cityArea></affiliation></author><author><name sortKey="Edagwa, Benson" sort="Edagwa, Benson" uniqKey="Edagwa B" first="Benson" last="Edagwa">Benson Edagwa</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0666 4105</institution-id><institution-id institution-id-type="GRID">grid.266813.8</institution-id><institution>Department of Pharmacology and Experimental Neuroscience,</institution><institution>University of Nebraska Medical Center,</institution></institution-wrap>Omaha, NE 68198-5880 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Nebraska</region></placeName><wicri:cityArea>Omaha</wicri:cityArea></affiliation></author><author><name sortKey="Khalili, Kamel" sort="Khalili, Kamel" uniqKey="Khalili K" first="Kamel" last="Khalili">Kamel Khalili</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2248 3398</institution-id><institution-id institution-id-type="GRID">grid.264727.2</institution-id><institution>Department of Neuroscience,</institution><institution>Lewis Katz School of Medicine at Temple University,</institution></institution-wrap>Philadelphia, PA 19115 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Philadelphia</wicri:cityArea></affiliation></author><author><name sortKey="Gendelman, Howard E" sort="Gendelman, Howard E" uniqKey="Gendelman H" first="Howard E." last="Gendelman">Howard E. 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Dash</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0666 4105</institution-id><institution-id institution-id-type="GRID">grid.266813.8</institution-id><institution>Department of Pharmacology and Experimental Neuroscience,</institution><institution>University of Nebraska Medical Center,</institution></institution-wrap>Omaha, NE 68198-5880 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Nebraska</region></placeName><wicri:cityArea>Omaha</wicri:cityArea></affiliation></author><author><name sortKey="Kaminski, Rafal" sort="Kaminski, Rafal" uniqKey="Kaminski R" first="Rafal" last="Kaminski">Rafal Kaminski</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2248 3398</institution-id><institution-id institution-id-type="GRID">grid.264727.2</institution-id><institution>Department of Neuroscience,</institution><institution>Lewis Katz School of Medicine at Temple University,</institution></institution-wrap>Philadelphia, PA 19115 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Philadelphia</wicri:cityArea></affiliation></author><author><name sortKey="Bella, Ramona" sort="Bella, Ramona" uniqKey="Bella R" first="Ramona" last="Bella">Ramona Bella</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2248 3398</institution-id><institution-id institution-id-type="GRID">grid.264727.2</institution-id><institution>Department of Neuroscience,</institution><institution>Lewis Katz School of Medicine at Temple University,</institution></institution-wrap>Philadelphia, PA 19115 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Philadelphia</wicri:cityArea></affiliation></author><author><name sortKey="Su, Hang" sort="Su, Hang" uniqKey="Su H" first="Hang" last="Su">Hang Su</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0666 4105</institution-id><institution-id institution-id-type="GRID">grid.266813.8</institution-id><institution>Department of Pharmacology and Experimental Neuroscience,</institution><institution>University of Nebraska Medical Center,</institution></institution-wrap>Omaha, NE 68198-5880 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Nebraska</region></placeName><wicri:cityArea>Omaha</wicri:cityArea></affiliation></author><author><name sortKey="Mathews, Saumi" sort="Mathews, Saumi" uniqKey="Mathews S" first="Saumi" last="Mathews">Saumi Mathews</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0666 4105</institution-id><institution-id institution-id-type="GRID">grid.266813.8</institution-id><institution>Department of Pharmacology and Experimental Neuroscience,</institution><institution>University of Nebraska Medical Center,</institution></institution-wrap>Omaha, NE 68198-5880 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Nebraska</region></placeName><wicri:cityArea>Omaha</wicri:cityArea></affiliation></author><author><name sortKey="Ahooyi, Taha M" sort="Ahooyi, Taha M" uniqKey="Ahooyi T" first="Taha M." last="Ahooyi">Taha M. Ahooyi</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2248 3398</institution-id><institution-id institution-id-type="GRID">grid.264727.2</institution-id><institution>Department of Neuroscience,</institution><institution>Lewis Katz School of Medicine at Temple University,</institution></institution-wrap>Philadelphia, PA 19115 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Philadelphia</wicri:cityArea></affiliation></author><author><name sortKey="Chen, Chen" sort="Chen, Chen" uniqKey="Chen C" first="Chen" last="Chen">Chen Chen</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2248 3398</institution-id><institution-id institution-id-type="GRID">grid.264727.2</institution-id><institution>Department of Neuroscience,</institution><institution>Lewis Katz School of Medicine at Temple University,</institution></institution-wrap>Philadelphia, PA 19115 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Philadelphia</wicri:cityArea></affiliation></author><author><name sortKey="Mancuso, Pietro" sort="Mancuso, Pietro" uniqKey="Mancuso P" first="Pietro" last="Mancuso">Pietro Mancuso</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2248 3398</institution-id><institution-id institution-id-type="GRID">grid.264727.2</institution-id><institution>Department of Neuroscience,</institution><institution>Lewis Katz School of Medicine at Temple University,</institution></institution-wrap>Philadelphia, PA 19115 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Philadelphia</wicri:cityArea></affiliation></author><author><name sortKey="Sariyer, Rahsan" sort="Sariyer, Rahsan" uniqKey="Sariyer R" first="Rahsan" last="Sariyer">Rahsan Sariyer</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2248 3398</institution-id><institution-id institution-id-type="GRID">grid.264727.2</institution-id><institution>Department of Neuroscience,</institution><institution>Lewis Katz School of Medicine at Temple University,</institution></institution-wrap>Philadelphia, PA 19115 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Philadelphia</wicri:cityArea></affiliation></author><author><name sortKey="Ferrante, Pasquale" sort="Ferrante, Pasquale" uniqKey="Ferrante P" first="Pasquale" last="Ferrante">Pasquale Ferrante</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2248 3398</institution-id><institution-id institution-id-type="GRID">grid.264727.2</institution-id><institution>Department of Neuroscience,</institution><institution>Lewis Katz School of Medicine at Temple University,</institution></institution-wrap>Philadelphia, PA 19115 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Philadelphia</wicri:cityArea></affiliation></author><author><name sortKey="Donadoni, Martina" sort="Donadoni, Martina" uniqKey="Donadoni M" first="Martina" last="Donadoni">Martina Donadoni</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2248 3398</institution-id><institution-id institution-id-type="GRID">grid.264727.2</institution-id><institution>Department of Neuroscience,</institution><institution>Lewis Katz School of Medicine at Temple University,</institution></institution-wrap>Philadelphia, PA 19115 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Philadelphia</wicri:cityArea></affiliation></author><author><name sortKey="Robinson, Jake A" sort="Robinson, Jake A" uniqKey="Robinson J" first="Jake A." last="Robinson">Jake A. Robinson</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2248 3398</institution-id><institution-id institution-id-type="GRID">grid.264727.2</institution-id><institution>Department of Neuroscience,</institution><institution>Lewis Katz School of Medicine at Temple University,</institution></institution-wrap>Philadelphia, PA 19115 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Philadelphia</wicri:cityArea></affiliation></author><author><name sortKey="Sillman, Brady" sort="Sillman, Brady" uniqKey="Sillman B" first="Brady" last="Sillman">Brady Sillman</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0666 4105</institution-id><institution-id institution-id-type="GRID">grid.266813.8</institution-id><institution>Department of Pharmacology and Experimental Neuroscience,</institution><institution>University of Nebraska Medical Center,</institution></institution-wrap>Omaha, NE 68198-5880 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Nebraska</region></placeName><wicri:cityArea>Omaha</wicri:cityArea></affiliation></author><author><name sortKey="Lin, Zhiyi" sort="Lin, Zhiyi" uniqKey="Lin Z" first="Zhiyi" last="Lin">Zhiyi Lin</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0666 4105</institution-id><institution-id institution-id-type="GRID">grid.266813.8</institution-id><institution>Department of Pharmacology and Experimental Neuroscience,</institution><institution>University of Nebraska Medical Center,</institution></institution-wrap>Omaha, NE 68198-5880 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Nebraska</region></placeName><wicri:cityArea>Omaha</wicri:cityArea></affiliation></author><author><name sortKey="Hilaire, James R" sort="Hilaire, James R" uniqKey="Hilaire J" first="James R." last="Hilaire">James R. Hilaire</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0666 4105</institution-id><institution-id institution-id-type="GRID">grid.266813.8</institution-id><institution>Department of Pharmacology and Experimental Neuroscience,</institution><institution>University of Nebraska Medical Center,</institution></institution-wrap>Omaha, NE 68198-5880 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Nebraska</region></placeName><wicri:cityArea>Omaha</wicri:cityArea></affiliation></author><author><name sortKey="Banoub, Mary" sort="Banoub, Mary" uniqKey="Banoub M" first="Mary" last="Banoub">Mary Banoub</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0666 4105</institution-id><institution-id institution-id-type="GRID">grid.266813.8</institution-id><institution>Department of Pharmacology and Experimental Neuroscience,</institution><institution>University of Nebraska Medical Center,</institution></institution-wrap>Omaha, NE 68198-5880 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Nebraska</region></placeName><wicri:cityArea>Omaha</wicri:cityArea></affiliation></author><author><name sortKey="Elango, Monalisha" sort="Elango, Monalisha" uniqKey="Elango M" first="Monalisha" last="Elango">Monalisha Elango</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0666 4105</institution-id><institution-id institution-id-type="GRID">grid.266813.8</institution-id><institution>Department of Pharmacology and Experimental Neuroscience,</institution><institution>University of Nebraska Medical Center,</institution></institution-wrap>Omaha, NE 68198-5880 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Nebraska</region></placeName><wicri:cityArea>Omaha</wicri:cityArea></affiliation></author><author><name sortKey="Gautam, Nagsen" sort="Gautam, Nagsen" uniqKey="Gautam N" first="Nagsen" last="Gautam">Nagsen Gautam</name><affiliation wicri:level="2"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0666 4105</institution-id><institution-id institution-id-type="GRID">grid.266813.8</institution-id><institution>Department of Pharmaceutical Sciences,</institution><institution>College of Pharmacy, University of Nebraska Medical Center,</institution></institution-wrap>Omaha, NE 68198-5880 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Nebraska</region></placeName><wicri:cityArea>Omaha</wicri:cityArea></affiliation></author><author><name sortKey="Mosley, R Lee" sort="Mosley, R Lee" uniqKey="Mosley R" first="R. Lee" last="Mosley">R. Lee Mosley</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0666 4105</institution-id><institution-id institution-id-type="GRID">grid.266813.8</institution-id><institution>Department of Pharmacology and Experimental Neuroscience,</institution><institution>University of Nebraska Medical Center,</institution></institution-wrap>Omaha, NE 68198-5880 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Nebraska</region></placeName><wicri:cityArea>Omaha</wicri:cityArea></affiliation></author><author><name sortKey="Poluektova, Larisa Y" sort="Poluektova, Larisa Y" uniqKey="Poluektova L" first="Larisa Y." last="Poluektova">Larisa Y. Poluektova</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0666 4105</institution-id><institution-id institution-id-type="GRID">grid.266813.8</institution-id><institution>Department of Pharmacology and Experimental Neuroscience,</institution><institution>University of Nebraska Medical Center,</institution></institution-wrap>Omaha, NE 68198-5880 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Nebraska</region></placeName><wicri:cityArea>Omaha</wicri:cityArea></affiliation></author><author><name sortKey="Mcmillan, Joellyn" sort="Mcmillan, Joellyn" uniqKey="Mcmillan J" first="Joellyn" last="Mcmillan">Joellyn Mcmillan</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0666 4105</institution-id><institution-id institution-id-type="GRID">grid.266813.8</institution-id><institution>Department of Pharmacology and Experimental Neuroscience,</institution><institution>University of Nebraska Medical Center,</institution></institution-wrap>Omaha, NE 68198-5880 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Nebraska</region></placeName><wicri:cityArea>Omaha</wicri:cityArea></affiliation></author><author><name sortKey="Bade, Aditya N" sort="Bade, Aditya N" uniqKey="Bade A" first="Aditya N." last="Bade">Aditya N. Bade</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0666 4105</institution-id><institution-id institution-id-type="GRID">grid.266813.8</institution-id><institution>Department of Pharmacology and Experimental Neuroscience,</institution><institution>University of Nebraska Medical Center,</institution></institution-wrap>Omaha, NE 68198-5880 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Nebraska</region></placeName><wicri:cityArea>Omaha</wicri:cityArea></affiliation></author><author><name sortKey="Gorantla, Santhi" sort="Gorantla, Santhi" uniqKey="Gorantla S" first="Santhi" last="Gorantla">Santhi Gorantla</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0666 4105</institution-id><institution-id institution-id-type="GRID">grid.266813.8</institution-id><institution>Department of Pharmacology and Experimental Neuroscience,</institution><institution>University of Nebraska Medical Center,</institution></institution-wrap>Omaha, NE 68198-5880 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Nebraska</region></placeName><wicri:cityArea>Omaha</wicri:cityArea></affiliation></author><author><name sortKey="Sariyer, Ilker K" sort="Sariyer, Ilker K" uniqKey="Sariyer I" first="Ilker K." last="Sariyer">Ilker K. Sariyer</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2248 3398</institution-id><institution-id institution-id-type="GRID">grid.264727.2</institution-id><institution>Department of Neuroscience,</institution><institution>Lewis Katz School of Medicine at Temple University,</institution></institution-wrap>Philadelphia, PA 19115 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Philadelphia</wicri:cityArea></affiliation></author><author><name sortKey="Burdo, Tricia H" sort="Burdo, Tricia H" uniqKey="Burdo T" first="Tricia H." last="Burdo">Tricia H. Burdo</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2248 3398</institution-id><institution-id institution-id-type="GRID">grid.264727.2</institution-id><institution>Department of Neuroscience,</institution><institution>Lewis Katz School of Medicine at Temple University,</institution></institution-wrap>Philadelphia, PA 19115 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Philadelphia</wicri:cityArea></affiliation></author><author><name sortKey="Young, Won Bin" sort="Young, Won Bin" uniqKey="Young W" first="Won-Bin" last="Young">Won-Bin Young</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2248 3398</institution-id><institution-id institution-id-type="GRID">grid.264727.2</institution-id><institution>Department of Neuroscience,</institution><institution>Lewis Katz School of Medicine at Temple University,</institution></institution-wrap>Philadelphia, PA 19115 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Philadelphia</wicri:cityArea></affiliation></author><author><name sortKey="Amini, Shohreh" sort="Amini, Shohreh" uniqKey="Amini S" first="Shohreh" last="Amini">Shohreh Amini</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2248 3398</institution-id><institution-id institution-id-type="GRID">grid.264727.2</institution-id><institution>Department of Neuroscience,</institution><institution>Lewis Katz School of Medicine at Temple University,</institution></institution-wrap>Philadelphia, PA 19115 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Philadelphia</wicri:cityArea></affiliation></author><author><name sortKey="Gordon, Jennifer" sort="Gordon, Jennifer" uniqKey="Gordon J" first="Jennifer" last="Gordon">Jennifer Gordon</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2248 3398</institution-id><institution-id institution-id-type="GRID">grid.264727.2</institution-id><institution>Department of Neuroscience,</institution><institution>Lewis Katz School of Medicine at Temple University,</institution></institution-wrap>Philadelphia, PA 19115 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Philadelphia</wicri:cityArea></affiliation></author><author><name sortKey="Jacobson, Jeffrey M" sort="Jacobson, Jeffrey M" uniqKey="Jacobson J" first="Jeffrey M." last="Jacobson">Jeffrey M. Jacobson</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2248 3398</institution-id><institution-id institution-id-type="GRID">grid.264727.2</institution-id><institution>Department of Neuroscience,</institution><institution>Lewis Katz School of Medicine at Temple University,</institution></institution-wrap>Philadelphia, PA 19115 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Philadelphia</wicri:cityArea></affiliation></author><author><name sortKey="Edagwa, Benson" sort="Edagwa, Benson" uniqKey="Edagwa B" first="Benson" last="Edagwa">Benson Edagwa</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0666 4105</institution-id><institution-id institution-id-type="GRID">grid.266813.8</institution-id><institution>Department of Pharmacology and Experimental Neuroscience,</institution><institution>University of Nebraska Medical Center,</institution></institution-wrap>Omaha, NE 68198-5880 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Nebraska</region></placeName><wicri:cityArea>Omaha</wicri:cityArea></affiliation></author><author><name sortKey="Khalili, Kamel" sort="Khalili, Kamel" uniqKey="Khalili K" first="Kamel" last="Khalili">Kamel Khalili</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2248 3398</institution-id><institution-id institution-id-type="GRID">grid.264727.2</institution-id><institution>Department of Neuroscience,</institution><institution>Lewis Katz School of Medicine at Temple University,</institution></institution-wrap>Philadelphia, PA 19115 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Philadelphia</wicri:cityArea></affiliation></author><author><name sortKey="Gendelman, Howard E" sort="Gendelman, Howard E" uniqKey="Gendelman H" first="Howard E." last="Gendelman">Howard E. Gendelman</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0666 4105</institution-id><institution-id institution-id-type="GRID">grid.266813.8</institution-id><institution>Department of Pharmacology and Experimental Neuroscience,</institution><institution>University of Nebraska Medical Center,</institution></institution-wrap>Omaha, NE 68198-5880 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Nebraska</region></placeName><wicri:cityArea>Omaha</wicri:cityArea></affiliation></author></analytic><series><title level="j">Nature Communications</title><idno type="eISSN">2041-1723</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="Par1">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. 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Gendelman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcmillan, J" uniqKey="Mcmillan J">J McMillan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dou, H" uniqKey="Dou H">H Dou</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dou, H" uniqKey="Dou H">H Dou</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Bella, R" uniqKey="Bella R">R Bella</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhou, T" uniqKey="Zhou T">T Zhou</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, G" uniqKey="Zhang G">G Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Puligujja, P" uniqKey="Puligujja P">P Puligujja</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Guo, D" uniqKey="Guo D">D Guo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nowacek, As" uniqKey="Nowacek A">AS Nowacek</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Nowacek, As" uniqKey="Nowacek A">AS Nowacek</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kevadiya, Bd" uniqKey="Kevadiya B">BD Kevadiya</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jacobson, Jm" uniqKey="Jacobson J">JM Jacobson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Byrareddy, Sn" uniqKey="Byrareddy S">SN Byrareddy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Honeycutt, Jb" uniqKey="Honeycutt J">JB Honeycutt</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="O Oherty, U" uniqKey="O Oherty U">U O’Doherty</name></author><author><name sortKey="Swiggard, Wj" uniqKey="Swiggard W">WJ Swiggard</name></author><author><name sortKey="Malim, Mh" uniqKey="Malim M">MH Malim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cohen, Ms" uniqKey="Cohen M">MS Cohen</name></author><author><name sortKey="Gay, Cl" uniqKey="Gay C">CL Gay</name></author><author><name sortKey="Busch, Mp" uniqKey="Busch M">MP Busch</name></author><author><name sortKey="Hecht, Fm" uniqKey="Hecht F">FM Hecht</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Agosto, Lm" uniqKey="Agosto L">LM Agosto</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pasternak, Ao" uniqKey="Pasternak A">AO Pasternak</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liszewski, Mk" uniqKey="Liszewski M">MK Liszewski</name></author><author><name sortKey="Yu, Jj" uniqKey="Yu J">JJ Yu</name></author><author><name sortKey="O Oherty, U" uniqKey="O Oherty U">U O’Doherty</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Deleage, C" uniqKey="Deleage C">C Deleage</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Buzon, Mj" uniqKey="Buzon M">MJ Buzon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Buzon, Mj" uniqKey="Buzon M">MJ Buzon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Laird, Gm" uniqKey="Laird G">GM Laird</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Nebraska</li><li>Pennsylvanie</li></region></list><tree><country name="États-Unis"><region name="Nebraska"><name sortKey="Dash, Prasanta K" sort="Dash, Prasanta K" uniqKey="Dash P" first="Prasanta K." last="Dash">Prasanta K. Dash</name></region><name sortKey="Ahooyi, Taha M" sort="Ahooyi, Taha M" uniqKey="Ahooyi T" first="Taha M." last="Ahooyi">Taha M. Ahooyi</name><name sortKey="Amini, Shohreh" sort="Amini, Shohreh" uniqKey="Amini S" first="Shohreh" last="Amini">Shohreh Amini</name><name sortKey="Bade, Aditya N" sort="Bade, Aditya N" uniqKey="Bade A" first="Aditya N." last="Bade">Aditya N. Bade</name><name sortKey="Banoub, Mary" sort="Banoub, Mary" uniqKey="Banoub M" first="Mary" last="Banoub">Mary Banoub</name><name sortKey="Bella, Ramona" sort="Bella, Ramona" uniqKey="Bella R" first="Ramona" last="Bella">Ramona Bella</name><name sortKey="Burdo, Tricia H" sort="Burdo, Tricia H" uniqKey="Burdo T" first="Tricia H." last="Burdo">Tricia H. Burdo</name><name sortKey="Chen, Chen" sort="Chen, Chen" uniqKey="Chen C" first="Chen" last="Chen">Chen Chen</name><name sortKey="Donadoni, Martina" sort="Donadoni, Martina" uniqKey="Donadoni M" first="Martina" last="Donadoni">Martina Donadoni</name><name sortKey="Edagwa, Benson" sort="Edagwa, Benson" uniqKey="Edagwa B" first="Benson" last="Edagwa">Benson Edagwa</name><name sortKey="Elango, Monalisha" sort="Elango, Monalisha" uniqKey="Elango M" first="Monalisha" last="Elango">Monalisha Elango</name><name sortKey="Ferrante, Pasquale" sort="Ferrante, Pasquale" uniqKey="Ferrante P" first="Pasquale" last="Ferrante">Pasquale Ferrante</name><name sortKey="Gautam, Nagsen" sort="Gautam, Nagsen" uniqKey="Gautam N" first="Nagsen" last="Gautam">Nagsen Gautam</name><name sortKey="Gendelman, Howard E" sort="Gendelman, Howard E" uniqKey="Gendelman H" first="Howard E." last="Gendelman">Howard E. Gendelman</name><name sortKey="Gorantla, Santhi" sort="Gorantla, Santhi" uniqKey="Gorantla S" first="Santhi" last="Gorantla">Santhi Gorantla</name><name sortKey="Gordon, Jennifer" sort="Gordon, Jennifer" uniqKey="Gordon J" first="Jennifer" last="Gordon">Jennifer Gordon</name><name sortKey="Hilaire, James R" sort="Hilaire, James R" uniqKey="Hilaire J" first="James R." last="Hilaire">James R. Hilaire</name><name sortKey="Jacobson, Jeffrey M" sort="Jacobson, Jeffrey M" uniqKey="Jacobson J" first="Jeffrey M." last="Jacobson">Jeffrey M. Jacobson</name><name sortKey="Kaminski, Rafal" sort="Kaminski, Rafal" uniqKey="Kaminski R" first="Rafal" last="Kaminski">Rafal Kaminski</name><name sortKey="Khalili, Kamel" sort="Khalili, Kamel" uniqKey="Khalili K" first="Kamel" last="Khalili">Kamel Khalili</name><name sortKey="Lin, Zhiyi" sort="Lin, Zhiyi" uniqKey="Lin Z" first="Zhiyi" last="Lin">Zhiyi Lin</name><name sortKey="Mancuso, Pietro" sort="Mancuso, Pietro" uniqKey="Mancuso P" first="Pietro" last="Mancuso">Pietro Mancuso</name><name sortKey="Mathews, Saumi" sort="Mathews, Saumi" uniqKey="Mathews S" first="Saumi" last="Mathews">Saumi Mathews</name><name sortKey="Mcmillan, Joellyn" sort="Mcmillan, Joellyn" uniqKey="Mcmillan J" first="Joellyn" last="Mcmillan">Joellyn Mcmillan</name><name sortKey="Mosley, R Lee" sort="Mosley, R Lee" uniqKey="Mosley R" first="R. Lee" last="Mosley">R. Lee Mosley</name><name sortKey="Poluektova, Larisa Y" sort="Poluektova, Larisa Y" uniqKey="Poluektova L" first="Larisa Y." last="Poluektova">Larisa Y. Poluektova</name><name sortKey="Robinson, Jake A" sort="Robinson, Jake A" uniqKey="Robinson J" first="Jake A." last="Robinson">Jake A. Robinson</name><name sortKey="Sariyer, Ilker K" sort="Sariyer, Ilker K" uniqKey="Sariyer I" first="Ilker K." last="Sariyer">Ilker K. Sariyer</name><name sortKey="Sariyer, Rahsan" sort="Sariyer, Rahsan" uniqKey="Sariyer R" first="Rahsan" last="Sariyer">Rahsan Sariyer</name><name sortKey="Sillman, Brady" sort="Sillman, Brady" uniqKey="Sillman B" first="Brady" last="Sillman">Brady Sillman</name><name sortKey="Su, Hang" sort="Su, Hang" uniqKey="Su H" first="Hang" last="Su">Hang Su</name><name sortKey="Young, Won Bin" sort="Young, Won Bin" uniqKey="Young W" first="Won-Bin" last="Young">Won-Bin Young</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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