CRISPR based editing of SIV proviral DNA in ART treated non-human primates
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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.
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Anti-Retroviral Agents / pharmacology
Base Sequence
CRISPR-Cas Systems / genetics
Cells, Cultured
DNA, Viral / blood
DNA, Viral / genetics
Gene Editing
Genome, Viral
Humans
Lung / drug effects
Lung / virology
Lymph Nodes / drug effects
Lymph Nodes / virology
Macaca mulatta
Proviruses / drug effects
Proviruses / genetics
Simian Acquired Immunodeficiency Syndrome / blood
Simian Acquired Immunodeficiency Syndrome / virology
Simian Immunodeficiency Virus / genetics
Spleen / pathology
Spleen / virology
Tissue Distribution
Transgenes