CRISPR based editing of SIV proviral DNA in ART treated non-human primates

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dc.creatorMancuso, Pietro
dc.creatorChen, Chen
dc.creatorKaminski, Rafal
dc.creatorGordon, Jennifer
dc.creatorLiao, Shuren
dc.creatorRobinson, Jake A.
dc.creatorSmith, Mandy D.
dc.creatorLiu, Hong
dc.creatorSariyer, Ilker K.
dc.creatorSariyer, Rahsan
dc.creatorPeterson, Tiffany A.
dc.creatorDonadoni, Martina
dc.creatorWilliams, Jaclyn B.
dc.creatorSiddiqui, Summer
dc.creatorBunnell, Bruce A.
dc.creatorLing, Binhua
dc.creatorMacLean, Andrew G.
dc.creatorBurdo, Tricia H.
dc.creatorKhalili, Kamel
dc.creator.orcid0000-0001-6196-3722 (Bunnell, Bruce A.)
dc.date.accessioned2022-08-25T15:39:45Z
dc.date.available2022-08-25T15:39:45Z
dc.date.issued2020-11-27
dc.description.abstractElimination of HIV DNA from infected individuals remains a challenge in medicine. Here, we demonstrate that intravenous inoculation of SIV-infected macaques, a well-accepted non-human primate model of HIV infection, with adeno-associated virus 9 (AAV9)-CRISPR/Cas9 gene editing construct designed for eliminating proviral SIV DNA, leads to broad distribution of editing molecules and precise cleavage and removal of fragments of the integrated proviral DNA from the genome of infected blood cells and tissues known to be viral reservoirs including lymph nodes, spleen, bone marrow, and brain among others. Accordingly, AAV9-CRISPR treatment results in a reduction in the percent of proviral DNA in blood and tissues. These proof-of-concept observations offer a promising step toward the elimination of HIV reservoirs in the clinic.
dc.description.sponsorshipThis work was supported by grant support from NIH: P51OD11104, R01NS104016, R56AI143647, R56AI150772, U42OD024282, U42OD010568, P30MH092177, and a Ruth L. Kirschstein National Research Service Award (5T32OD011124-13).
dc.identifier.citationMancuso, P., Chen, C., Kaminski, R., Gordon, J., Liao, S., Robinson, J. A., Smith, M. D., Liu, H., Sariyer, I. K., Sariyer, R., Peterson, T. A., Donadoni, M., Williams, J. B., Siddiqui, S., Bunnell, B. A., Ling, B., MacLean, A. G., Burdo, T. H., & Khalili, K. (2020). CRISPR based editing of SIV proviral DNA in ART treated non-human primates. Nature communications, 11(1), 6065. https://doi.org/10.1038/s41467-020-19821-7
dc.identifier.issn2041-1723
dc.identifier.issue1
dc.identifier.urihttps://hdl.handle.net/20.500.12503/31644
dc.identifier.volume11
dc.publisherSpringer Nature
dc.relation.urihttps://doi.org/10.1038/s41467-020-19821-7
dc.rights.holder© The Author(s) 2020
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceNature Communications
dc.subject.meshAnimals
dc.subject.meshAnti-Retroviral Agents / pharmacology
dc.subject.meshBase Sequence
dc.subject.meshCRISPR-Cas Systems / genetics
dc.subject.meshCells, Cultured
dc.subject.meshDNA, Viral / blood
dc.subject.meshDNA, Viral / genetics
dc.subject.meshGene Editing
dc.subject.meshGenome, Viral
dc.subject.meshHumans
dc.subject.meshLung / drug effects
dc.subject.meshLung / virology
dc.subject.meshLymph Nodes / drug effects
dc.subject.meshLymph Nodes / virology
dc.subject.meshMacaca mulatta
dc.subject.meshProviruses / drug effects
dc.subject.meshProviruses / genetics
dc.subject.meshSimian Acquired Immunodeficiency Syndrome / blood
dc.subject.meshSimian Acquired Immunodeficiency Syndrome / virology
dc.subject.meshSimian Immunodeficiency Virus / genetics
dc.subject.meshSpleen / pathology
dc.subject.meshSpleen / virology
dc.subject.meshTissue Distribution
dc.subject.meshTransgenes
dc.titleCRISPR based editing of SIV proviral DNA in ART treated non-human primates
dc.typeArticle
dc.type.materialtext

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