Type I interferon response against viral and non-viral gene transfer in human tumor and primary cell lines
Type I interferon response against viral and non-viral gene transfer in human tumor and primary cell lines
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DOI：
10.1002/jgm.997
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发表时间：
2007-02-01
影响因子：
3.5
通讯作者：
Pellinen, Riikka
中科院分区：
文献类型：
--
作者：
Rautsi, Outi;Lehmusvaara, Saara;Pellinen, Riikka
背景I型干扰素（IFN-α/β）应答是宿主抵抗病毒的主要防御机制之一。最近的一些报道表明，干扰素可能会干扰非病毒和病毒载体介导的治疗性基因transfer.Methods的疗效后，不同的基因转移方法在肿瘤和原代细胞系的I型干扰素反应进行了研究，通过分析IFN-β mRNA人。结果用无毒的Semliki Forest病毒A7[74]感染诱导MxA蛋白积累并增加IFN-β mRNA水平，而所研究的病毒载体（腺病毒、CRAd、慢病毒或AAV）均不诱导IFN应答。然而，当用几种商业转染试剂转染时，质粒DNA诱导MxA蛋白的积累。RNA转染似乎是I型IFN应答的有效诱导剂：复制甲病毒RNA、真核细胞总RNA或mRNA均诱导MxA蛋白积累和IFN-β表达。siRNA转染未能诱导MxA response.Conclusions非病毒基因转移方法获得了更多的兴趣，在最近几年，由于其更好的安全性相比，他们的病毒同行。然而，非病毒基因转移的效率远低于病毒载体系统所达到的效率。由非病毒方法诱导的I型干扰素应答可能部分导致这种低效率，而目前使用的大多数病毒基因转移载体不能诱导或能够抑制I型IFN应答。版权所有（c）2006约翰威利父子有限公司。
Background Type I interferon (IFN-alpha/beta) response is one of the major host defence mechanisms against viruses. Some recent reports suggest that IFNs may interfere with the efficacy of both non-viral and virus-vector-mediated therapeutic gene transfer.Methods The type I IFN response upon different gene transfer methods in tumor and primary cell lines was studied by analysing IFN-beta mRNA human. expression, secretion of type I IFNs and accumulation of IFN-alpha/beta-induced MxA protein (myxovirus resistance protein A).Results Infection with avirulent Semliki Forest virus A7[74] induced MxA protein accumulation and increased the IFN-beta mRNA level, whereas none of the studied virus vectors (adenovirus, CRAd, lentivirus or AAV) induced IFN response. However, plasmid DNA induced the accumulation of MxA protein when transfected with several commercial transfection reagents. RNA transfection appeared to be an efficient inducer of type I IFN response: replicating alphaviral RNA, eukaryotic total RNA, or mRNA all induced both MxA protein accumulation and IFN-beta expression. siRNA transfection failed to induce MxA response.Conclusions The non-viral gene transfer methods have gained more interest in recent years due to their better safety profiles when compared to their viral counterparts. However, the efficiency of non-viral gene transfer is well below those reached by viral vector systems. The type I interferon response induced by non-viral methods may in part contribute to this inefficiency, while most currently used viral gene transfer vectors fail to induce or are able to suppress type I IFN response. Copyright (c) 2006 John Wiley & Sons, Ltd.