ANTI-HCMV ACTIVITY OF TRIPLE HELIX-FORMING OLIGOS

这个项目的目的是测试使用三螺旋的可行性。 (三链)形成寡核苷酸作为抗人类病毒药物 巨细胞病毒。寡核苷酸很早以前就被认为能够 与双链DNA结合形成三螺旋复合体。三链结构的研究进展 现在的技术允许设计形成三链的寡核苷酸 在生理条件下能够与复杂的DNA双链序列结合 条件。形成三链的寡核苷酸与双链DNA的结合 已被证明通过位点特异性DNA结合来破坏与该双链的结合 并在几个系统中抑制基因表达。我们打算 检测三链形成的寡核苷酸抑制病毒基因的能力 在细胞培养系统中的表达和病毒生长。 形成三链的寡核苷酸将被设计成破坏特定病毒 转录起始和/或延伸事件以及病毒DNA 人巨细胞病毒的复制事件。这些寡聚核苷酸将 被合成并分析为对合成的实际结合能力 靶序列在体外，然后在细胞内作为抗病毒药物进行检测 文化。任何能够抑制病毒的三链形成的寡核苷酸 细胞培养中的生长分析将通过第一阶段研究和 在动物模型中进一步评估作为抗病毒药物的作用 系统。这项技术在抗病毒药物开发中的应用 是抗病毒药物设计的一种创新方法。

The aim of this project is to test the feasibility of using triple helix (triplex)-forming oligonucleotides as antiviral agents against human cytomegalovirus. Oligonucleotides have long been known to be capable of binding to duplex DNA to form triple helix complexes. Advances in triplex technology now allows the design of triplex-forming oligonucleotides capable of binding with complex DNA duplex sequences under physiological conditions. Binding by triplex-forming oligonucleotides to duplex DNA has been shown to disrupt binding to that duplex by site specific DNA binding proteins and to inhibit gene expression in several systems. We intend to test the ability of triplex-forming oligonucleotides to inhibit viral gene expression and virus growth in cell culture systems. Triplex-forming oligonuceotides will be designed to disrupt specific viral transcription initiation and/or elongation events as well as viral DNA replication events of human cytomegalovirus. These oligonculeotides will be synthesized and analyzed for the actual binding ability to synthetic target sequences in vitro, and then assayed as anti-viral agents in cell culture. Any triplex-forming oligonucleotide capable of inhibiting viral growth in cell culture assays will have passed the Phase I studies and proceed to further evaluation as an antiviral agent in an animal model system. The use of this technology for the development of antiviral agents is an innovative approach to the design of antiviral drugs.