日本研究人員成功地利用人工酶作為“剪刀”，切斷了引發(fā)宮頸癌的人乳頭瘤病毒的DNA,，從而遏制了其增殖。這一技術(shù)有望應(yīng)用于治療由DNA病毒引起的疾病,。
宮頸癌是女性最常見(jiàn)的惡性腫瘤,，人乳頭瘤病毒是引發(fā)宮頸癌的主要原因。人乳頭瘤病毒是一種球形DNA病毒,，所謂DNA病毒是核酸為單鏈或雙鏈DNA的一種病毒,，廣泛存在于人、脊椎動(dòng)物,、昆蟲(chóng)體內(nèi)以及多種傳代細(xì)胞系中,，它無(wú)法單獨(dú)繁殖,，必須寄生在活細(xì)胞內(nèi),。
日本岡山大學(xué)的一個(gè)研究小組人工合成出一種“限制性核酸內(nèi)切酶”，可以將糖分子與磷酸之間的鍵結(jié)“剪斷”,，從而將雙鏈DNA“切斷”,。將這種人工酶植入人類細(xì)胞，它就與人乳頭瘤病毒的DNA結(jié)合在一起,，在特定部位將其切斷,，讓病毒的增殖水平降低到通常水平的4％左右。
研究負(fù)責(zé)人世良貴史說(shuō)：“即使病毒侵入人體,，只要不增殖就不會(huì)發(fā)病,。使用這種人工酶，即使是新型病毒,，只要弄清DNA排列的一部分,，就可以將其切斷，從而容易作為抗病毒藥物使用。”
相關(guān)論文已經(jīng)刊登在美國(guó)《科學(xué)公共圖書(shū)館—綜合卷》上（PLOS ONE）,。(生物谷Bioon.com)
doi:10.1371/journal.pone.0002917
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Systemic Therapy for Cervical Cancer with Potentially Regulatable Oncolytic Adenoviruses
Anna Kanerva, Sergio Lavilla-Alonso,Mari Raki, Lotta Kangasniemi, Gerd J. Bauerschmitz, Koichi Takayama, Ari Ristimaki, Renee A-Desmond, Akseli Hemminki.
Clinical trials have confirmed the safety of selectively oncolytic adenoviruses for treatment of advanced cancers. However, increasingly effective viruses could result in more toxicity and therefore it would be useful if replication could be abrogated if necessary. We analyzed viruses containing the cyclooxygenase-2 (Cox-2) or vascular endothelial growth factor (VEGF) promoter for controlling replication. Anti-inflammatory agents can lower Cox-2 protein levels and therefore we hypothesized that also the promoter might be affected. As Cox-2 modulates expression of VEGF, also the VEGF promoter might be controllable. First, we evaluated the effect of anti-inflammatory agents on promoter activity or adenovirus infectivity in vitro. Further, we analyzed the oncolytic potency of the viruses in vitro and in vivo with and without the reagents. Moreover, the effect of on virus replication was analyzed. We found that RGD-4C or Ad5/3 modified fibers improved the oncolytic potency of the viruses in vitro and in vivo. We found that both promoters could be downregulated with dexamethasone, sodium salicylate, or salicylic acid. Oncolytic efficacy correlated with the promoter activity and in vitro virus production could be abrogated with the substances. In vivo, we saw good therapeutic efficacy of the viruses in a model of intravenous therapy of metastatic cervical cancer, but the inhibitory effect of dexamethasone was not strong enough to provide significant differences in a complex in vivo environment. Our results suggest that anti-inflammatory drugs may affect the replication of adenovirus, which might be relevant in case of replication associated side effects.
