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

Pietro Mancuso, Chen Chen, Rafal Kaminski, Jennifer Gordon, Shuren Liao, Jake A. Robinson, Mandy D. Smith, Hong Liu, Ilker K. Sariyer, Rahsan Sariyer, Tiffany A. Peterson, Martina Donadoni, Jaclyn B. Williams, Summer Siddiqui, Bruce A. Bunnell, Binhua Ling (), Andrew G. MacLean (), Tricia H. Burdo () and Kamel Khalili ()
Additional contact information
Pietro Mancuso: Lewis Katz School of Medicine at Temple University
Chen Chen: Lewis Katz School of Medicine at Temple University
Rafal Kaminski: Lewis Katz School of Medicine at Temple University
Jennifer Gordon: Lewis Katz School of Medicine at Temple University
Shuren Liao: Lewis Katz School of Medicine at Temple University
Jake A. Robinson: Lewis Katz School of Medicine at Temple University
Mandy D. Smith: Lewis Katz School of Medicine at Temple University
Hong Liu: Lewis Katz School of Medicine at Temple University
Ilker K. Sariyer: Lewis Katz School of Medicine at Temple University
Rahsan Sariyer: Lewis Katz School of Medicine at Temple University
Tiffany A. Peterson: Tulane National Primate Research Center
Martina Donadoni: Lewis Katz School of Medicine at Temple University
Jaclyn B. Williams: Tulane National Primate Research Center
Summer Siddiqui: Tulane National Primate Research Center
Bruce A. Bunnell: Tulane National Primate Research Center
Binhua Ling: Tulane National Primate Research Center
Andrew G. MacLean: Tulane National Primate Research Center
Tricia H. Burdo: Lewis Katz School of Medicine at Temple University
Kamel Khalili: Lewis Katz School of Medicine at Temple University

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-19821-7

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