近日,，中南大學(xué)湘雅醫(yī)院教授郭曲練課題組運(yùn)用核酸干擾（RNAi）技術(shù)首次構(gòu)建了一種新載體，對(duì)一種關(guān)鍵致痛基因?qū)崿F(xiàn)成功抑制,，目前已獲國(guó)家發(fā)明專利,。
相關(guān)成果在《基因醫(yī)學(xué)雜志》、《人類基因治療》(Human Gene Therapy)等國(guó)際權(quán)威期刊發(fā)表后,，迅速引起美,、澳等國(guó)醫(yī)學(xué)界的密切關(guān)注，評(píng)審專家稱其“設(shè)計(jì)巧妙,，有巨大的臨床潛力”,。
據(jù)了解，自2006年核酸干擾原理的發(fā)現(xiàn)獲諾貝爾醫(yī)學(xué)獎(jiǎng)以來(lái),，基因靶向治療日益成為國(guó)際醫(yī)學(xué)界競(jìng)相追逐的前沿,，但目前仍處在實(shí)驗(yàn)室研究階段，在慢性疼痛領(lǐng)域未見(jiàn)成功報(bào)道,。
而中南大學(xué)此項(xiàng)成果為該類疾病的基因治療開(kāi)辟了道路,。該療法針對(duì)的致痛基因PKCγ,，是目前人類已經(jīng)發(fā)現(xiàn)的十余種神經(jīng)性疼痛致痛基因之一，在神經(jīng)中樞起著關(guān)鍵的信號(hào)轉(zhuǎn)導(dǎo)作用,。郭曲練課題組在大鼠試驗(yàn)中發(fā)現(xiàn),，小發(fā)夾核酸對(duì)目標(biāo)實(shí)施了精確“干擾”，不僅使注射嗎啡產(chǎn)生的藥物耐受性大大降低,，而且顯著“阻斷”了PKCγ基因的自身表達(dá),，使致痛基因“失效”達(dá)6個(gè)星期之久。（生物谷Bioon.com）
doi:10.1089/hum.2010.207
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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.
