Novel SiRNA microbicides to prevent /treat HPV infection

用于预防/治疗 HPV 感染的新型 SiRNA 杀菌剂

• 批准号: 7132117
• 负责人: PAUL F. LAMBERT
• 金额: $ 11.47万
• 依托单位: RHODE ISLAND HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7132117
• 关键词: Macaca mulatta; RNA interference; antiviral agents; biotechnology; communicable disease control; cooperative study; disease /disorder model; female reproductive system; genotype; human papillomavirus; laboratory mouse; mucosa; nucleic acid sequence; oncogenes; plasmids; sexually transmitted diseases; small interfering RNA; technology /technique development; tissue /cell culture; virus DNA; virus diseases; virus genetics; virus infection mechanism; virus related neoplasm /cancer

Human papillomaviruses (HPVs) are one the most common sexually transmitted diseases. These small DNA tumor viruses also are the causal agents for virtually all cervical cancers, other anogenital cancers, and a subset of oral cancers. The same subset of 'high risk' HPVs contribute to all of these cancers, with HPV16 being the virus genotype most commonly associated with each cancer. In this project we will determine whether the inhibition of expression of viral genes implicated in an early step of viral infection, the establishment of the viral genome as a nuclear plasmid, can lead to a reduced rate of infection. For these proof of principle studies, we will establish assays for monitoring the effect of siRNAs designed to knockdown expression of relevant papillomaviral genes, optimize the delivery of siRNAs to mucosal epithelia of the female reproductive tract and monitor the efficacy of papillomaviral-specific siRNAs in inhibiting genital infections by Rhesus papillomavirus (RhPV) in its cognate host. RhPV represents the closest animal model virus for studying the infection by anogenital HPVs. From these studies we will learn whether interference with the establishment of the papillomavirus DNA as a replicon in infected cells can reduce the onset of disease.

人乳头瘤病毒（HPV）是最常见的性传播疾病。这些 小型DNA肿瘤病毒也是几乎所有宫颈癌的因果剂，其他 肛门癌和口服癌的子集。同一子集的“高风险” HPV有助于 所有这些癌症，HPV16是最常见的病毒基因型 癌症。在这个项目中，我们将确定抑制病毒基因的表达 与病毒感染的早期一步有关，将病毒基因组建立为核 质粒会导致感染率降低。对于这些原则研究的证明，我们将 建立监测siRNA的效果的测定法 乳头瘤病毒基因，优化siRNA向雌性粘膜上皮的递送 生殖道并监测乳头状瘤特异性siRNA在抑制生殖器方面的功效 恒河状乳头瘤病毒（RHPV）的感染。 RHPV代表最接近 动物模型病毒用于研究肛门生殖器HPV的感染。从这些研究我们将学习 是否干扰乳头瘤病毒DNA作为感染中的复制子 细胞可以减少疾病的发作。