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

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Chen, Chen
; ; 
Gordon, Jennifer
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Liao, Shuren
; 
Robinson, Jake A.
; 
Smith, Mandy D.
; 
Liu, Hong
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Sariyer, Rahsan
; 
Peterson, Tiffany A.
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Genre
Journal article
Date
2020-11-27
Advisor
Committee member
Group
Center for Neurovirology (Temple University)
Department
Neuroscience
Subject
Drug delivery
 Experimental models of disease
 Gene therapy
 HIV infections
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http://hdl.handle.net/20.500.12613/4189
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Mancuso-JournalArticle-2020-11.pdf
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DOI
https://doi.org/10.1038/s41467-020-19821-7
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.
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Citation
Mancuso, P., Chen, C., Kaminski, R. et al. CRISPR based editing of SIV proviral DNA in ART treated non-human primates. Nat Commun 11, 6065 (2020). https://doi.org/10.1038/s41467-020-19821-7
Citation to related work
Nature
Featured by Temple Now: https://news.temple.edu/2020-11-28/researchers-make-hiv-breakthrough
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Nature Communications, Vol. 11, Article number: 6065 (2020)
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