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

Author:

Mancuso PietroORCID,Chen Chen,Kaminski RafalORCID,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 BinhuaORCID,MacLean Andrew G.ORCID,Burdo Tricia H.ORCID,Khalili KamelORCID

Abstract

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.

Funder

U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke

Division of Intramural Research, National Institute of Allergy and Infectious Diseases

U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases

U.S. Department of Health & Human Services | NIH | National Institute of Mental Health

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry

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