ANTI-HCMV ACTIVITY OF TRIPLE HELIX-FORMING OLIGOS

三螺旋形成寡核苷酸的抗 HCMV 活性

• 批准号: 3489795
• 负责人: Robert Rando
• 金额: $ 4万
• 依托单位: TRIPLEX PHARMACEUTICAL CORPORATION
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-01 至 1994-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3489795
• 关键词: DNA replication; antiviral agents; cytomegalovirus; drug design /synthesis /production; genetic transcription; nucleic acid structure; oligonucleotides; tissue /cell culture; virus assembly

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.

该项目的目的是测试使用三螺旋的可行性 （三链体）形成寡核苷酸作为人类抗病毒剂 巨细胞病毒。人们早就知道寡核苷酸能够 与双链 DNA 结合形成三螺旋复合物。三重体的进展 技术现在允许设计三链体形成的寡核苷酸 能够在生理条件下与复杂的DNA双链体序列结合 状况。通过形成三链体的寡核苷酸与双链体 DNA 的结合 已被证明可以通过位点特异性 DNA 结合破坏与该双链体的结合 蛋白质并抑制多个系统中的基因表达。我们打算 测试三链体形成寡核苷酸抑制病毒基因的能力 细胞培养系统中的表达和病毒生长。 三链体形成的寡核苷酸将被设计来破坏特定的病毒 转录起始和/或延伸事件以及病毒 DNA 人类巨细胞病毒的复制事件。这些寡核苷酸将 进行合成并分析其与合成物的实际结合能力 体外靶序列，然后在细胞中作为抗病毒剂进行测定 文化。任何能够抑制病毒的三链体形成寡核苷酸 细胞培养测定中的生长将通过第一阶段研究并且 继续在动物模型中进一步评估其作为抗病毒药物的作用 系统。利用该技术开发抗病毒药物 是一种抗病毒药物设计的创新方法。