Intracerebral Infusion of Antisense Oligonucleotides Into Prion-infected Mice
Intracerebral Infusion of Antisense Oligonucleotides Into Prion-infected Mice
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DOI：
10.1038/mtna.2011.6
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发表时间：
2012-02-01
影响因子：
8.8
通讯作者：
Prusiner, Stanley B.
中科院分区：
文献类型：
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作者：
Friberg, Karah Nazor;Hung, Gene;Prusiner, Stanley B.
缺乏细胞朊病毒蛋白（PrPc）的小鼠不会患上朊病毒病；因此，基于基因的减少 PrPC 表达的策略引起了人们的兴趣。我们合成了一系列针对小鼠 Prnp 信使 RNA (mRNA) 的化学修饰反义寡核苷酸 (ASO)，并鉴定了那些最有效降低 PrPc 表达的寡核苷酸。还在感染痒病的培养细胞 (ScN2a) 中评估了这些 ASO 在降低致病朊病毒蛋白 (PrPSc) 水平方面的功效。当从落基山实验室 (RML) 小鼠朊病毒株感染后 1 天开始，将最佳 ASO 注入 FVB 小鼠脑内，持续 14 天，观察到潜伏期延长了近 2 个月。 ASO 是否可用于为死于克雅氏病的患者开发有效疗法仍有待确定。
Mice deficient for the cellular prion protein (PrPc) do not develop prion disease; accordingly, gene-based strategies to diminish PrPC expression are of interest. We synthesized a series of chemically modified antisense oligonucleotides (ASOs) targeted against mouse Prnp messenger RNA (mRNA) and identified those that were most effective in decreasing PrPc expression. Those ASOs were also evaluated in scrapie-infected cultured cells (ScN2a) for their efficacy in diminishing the levels of the disease-causing prion protein (PrPSc). When the optimal ASO was infused intracerebrally into FVB mice over a 14-day period beginning 1 day after infection with the Rocky Mountain Laboratory (RML) strain of mouse prions, a prolongation of the incubation period of almost 2 months was observed. Whether ASOs can be used to develop an effective therapy for patients dying of CreutzfeldtJakob disease remains to be established.