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Mancuso P , Chen C , Kaminski R , Gordon J , Liao S , Robinson JA , Smith MD , Liu H , Sariyer IK , Sariyer R , Peterson TA , Donadoni M , Williams JB , Siddiqui S , Bunnell BA , Ling B , MacLean AG , Burdo TH , Khalili K
CRISPR based editing of SIV proviral DNA in ART treated non-human primates
Nat Commun. 2020 Nov 27;11(1) :6065
PMID: 33247091    PMCID: PMC7695718    URL: https://www.ncbi.nlm.nih.gov/pubmed/33247091
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Abstract
Elimination 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.
Notes
2041-1723 Mancuso, Pietro Orcid: 0000-0001-7079-9848 Chen, Chen Kaminski, Rafal Orcid: 0000-0001-8827-6658 Gordon, Jennifer Liao, Shuren Robinson, Jake A Smith, Mandy D Liu, Hong Sariyer, Ilker K Sariyer, Rahsan Peterson, Tiffany A Donadoni, Martina Williams, Jaclyn B Siddiqui, Summer Bunnell, Bruce A Ling, Binhua Orcid: 0000-0002-2259-8889 MacLean, Andrew G Orcid: 0000-0002-0356-0674 Burdo, Tricia H Orcid: 0000-0002-4224-7381 Khalili, Kamel Orcid: 0000-0002-6819-5217 U42 OD024282/OD/NIH HHS/United States P51 OD011104/OD/NIH HHS/United States R56 AI150772/AI/NIAID NIH HHS/United States R01 MH116844/MH/NIMH NIH HHS/United States U42 OD010568/OD/NIH HHS/United States P30 MH092177/MH/NIMH NIH HHS/United States R01 NS104016/NS/NINDS NIH HHS/United States T32 OD011124/OD/NIH HHS/United States R56 AI143647/AI/NIAID NIH HHS/United States Journal Article Research Support, N.I.H., Extramural England Nat Commun. 2020 Nov 27;11(1):6065. doi: 10.1038/s41467-020-19821-7.