Kim Veronica, Mears Brian M, Powell Bonita H, Witwer Kenneth W
Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine.
Matters (Zur). 2017;2017. doi: 10.19185/matters.201611000027. Epub 2017 Jan 12.
CRISPR/Cas9 systems have been advanced as promising tools in the HIV eradication armamentarium for sequence-specific disruption or latency reversal. Enthusiasm is balanced by concerns about off-target host genome modification and effects on HIV evolution. In the chronically HIV-1-infected U1 promonocytic latency model, we have confirmed stimulation of HIV-1 production by a mutant Cas9-transcriptional activator and guide RNAs with two guide RNAs apparently more potent than one. However, significant increases were also observed in the absence of guide RNAs. We encourage continued careful evaluation of non-sequence-specific and off-target effects of Cas9-mediated approaches.
CRISPR/Cas9系统已成为艾滋病根除武器库中用于序列特异性破坏或潜伏逆转的有前景的工具。对脱靶宿主基因组修饰及对HIV进化影响的担忧，平衡了人们的热情。在慢性HIV-1感染的U1单核细胞潜伏模型中，我们已证实一种突变型Cas9转录激活因子和引导RNA可刺激HIV-1产生，其中两个引导RNA的效果明显强于一个。然而，在没有引导RNA的情况下也观察到了显著增加。我们鼓励继续仔细评估Cas9介导方法的非序列特异性和脱靶效应。
