Targeting HPV16 DNA using CRISPR/Cas inhibits anal cancer growth in vivo.

Targeting HPV16 DNA using CRISPR/Cas inhibits anal cancer growth in vivo.
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DOI:
10.2217/fvl-2018-0010
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发表时间:
2018-07
期刊:
影响因子:
3.1
通讯作者:
Cullen BR
Cullen BR
中科院分区:
医学4区
文献类型:
--
作者:
Hsu DS;Kornepati AV;Glover W;Kennedy EM;Cullen BR

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本研究的目的是确定一个编码Cas9和HPV16 E6和E7基因特异性引导rna的AAV载体是否能在体内抑制HPV16诱导的肿瘤的生长。我们在免疫缺陷小鼠中培养HPV16+患者来源的肛门癌外植体,然后通过注射编码Cas9和对照或HPV16特异性引导rna的基于aav的载体来攻击这些外植体。我们观察到,当使用Cas9靶向HPV16 E6和E7基因时,肿瘤生长显著且选择性地减少。这些研究为CRISPR/Cas有可能用于选择性治疗人类hpv诱导肿瘤的假设提供了原理证明。
The goal of this study was to determine if a single AAV vector, encoding Cas9 and guide RNAs specific for the HPV16 E6 and E7 genes, could inhibit the growth of an HPV16-induced tumor in vivo. We grew HPV16+, patient-derived anal cancer explants in immunodeficient mice and then challenged these by injection of AAV-based vectors encoding Cas9 and control or HPV16-specific guide RNAs. We observed a significant and selective reduction in tumor growth when the HPV16 E6 and E7 genes were targeted using Cas9. These studies provide proof of principle for the hypothesis that CRISPR/Cas has the potential to be used to selectively treat HPV-induced tumors in humans.
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