Department of Neuroscience, Center for Neurovirology, Lewis Katz School of Medicine at Temple University, 3500N. Broad Street, 7th Floor, Philadelphia, PA, 19140, USA.
Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA, 70433, USA.
Nat Commun. 2020 Nov 27;11(1):6065. doi: 10.1038/s41467-020-19821-7.
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.
从受感染个体中清除 HIV 病毒仍然是医学领域的一个挑战。在这里，我们证明了通过静脉内接种携带 SIV 感染的猕猴（一种被广泛接受的 HIV 感染的非人类灵长类动物模型），用腺相关病毒 9（AAV9）-CRISPR/Cas9 基因编辑构建体进行治疗，该构建体旨在消除前病毒 SIV DNA，可导致编辑分子的广泛分布，以及对整合前病毒 DNA 片段的精确切割和从已知是病毒储存库的受感染血细胞和组织（包括淋巴结、脾脏、骨髓和大脑等）的基因组中去除。因此，AAV9-CRISPR 治疗可降低血液和组织中前病毒 DNA 的百分比。这些概念验证观察结果为在临床上消除 HIV 储存库提供了一个有前途的步骤。
