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核酸干扰(RNAi)技术成功抑制一种关键致痛基因

2011/11/30 来源:光明网
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中南大学湘雅医院教授郭曲练课题组运用核酸干扰(RNAi)技术首次构建了一种新载体,对一种关键致痛基因实现成功抑制,目前已获国家发明专利。

中南大学湘雅医院教授郭曲练课题组运用核酸干扰(RNAi)技术首次构建了一种新载体,对一种关键致痛基因实现成功抑制,目前已获国家发明专利。

相关成果在《基因医学杂志》、《人类基因治疗杂志》等国际权威期刊发表后,迅速引起美、澳等国医学界的密切关注,评审专家称其“设计巧妙,有巨大的临床潜力”。

据了解,自2006年核酸干扰原理的发现获诺贝尔医学奖以来,基因靶向治疗日益成为国际医学界竞相追逐的前沿,但目前仍处在实验室研究阶段,在慢性疼痛领域未见成功报道。

而中南大学此项成果为该类疾病的基因治疗开辟了道路。该疗法针对的致痛基因PKCγ,是目前人类已经发现的十余种神经性疼痛致痛基因之一,在神经中枢起着关键的信号转导作用。郭曲练课题组在大鼠试验中发现,小发夹核酸对目标实施了精确“干扰”,不仅使注射吗啡产生的药物耐受性大大降低,而且显著“阻断”了PKCγ基因的自身表达,使致痛基因“失效”达6个星期之久。

Intrathecal Lentiviral-Mediated RNA Interference Targeting PKCγ Attenuates Chronic Constriction Injury–Induced Neuropathic Pain in Rats

Wangyuan Zou, Zongbin Song, Qulian Guo, Chang Liu, Zhong Zhang, and Yanfeng Zhang.

In the spinal cord, protein kinase C isoform γ (PKCγ) plays an important role in the development of central pain sensitization. However, there are currently no specific PKCγ inhibitors available. Therefore, the aim of the present study was to assess the role of PKCγ in the modulation of pain using a more selective experimental tool. Although small interfering RNAs have been used to silence genes in neurons, in vivo delivery of RNA interference (RNAi) remains a major challenge, thus limiting its applications. Here we developed a highly efficient method of lentiviral-mediated delivery of short-hairpin RNAs targeting PKCγ for in vivo gene silencing in the spinal cord of rats. This method decreased the expression of PKCγ mRNA and protein, and additionally attenuated chronic constriction injury–induced mechanical allodynia and thermal hyperalgesia for more than 6 weeks. Our study suggests that PKCγ is a potential RNAi target for neuropathic pain. Furthermore, the lentiviral vector delivery strategy holds great promise as a novel approach for the treatment of neuropathic pain and study of PKCγ gene function.

文献链接:http://www.liebertonline.com/doi/abs/10.1089/hum.2010.207

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