Analysis of EBNA1 siRNA for inhibiting NPC tumor growth

EBNA1 siRNA 抑制鼻咽癌肿瘤生长的分析

• 批准号: 7085530
• 负责人: ERIK K FLEMINGTON
• 金额: $ 18.13万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7085530
• 关键词: Epstein Barr virus; RNA interference; antineoplastics; biotherapeutic agent; carcinoma; drug screening /evaluation; laboratory mouse; nasopharyngeal neoplasms; neoplastic growth; small interfering RNA; virus antigen; virus related neoplasm /cancer

DESCRIPTION (provided by applicant): The Epstein Barr virus (EBV) is strongly associated with nasopharyngeal carcinoma (NPC) and plays a key role in the genesis and maintenance of the tumor phenotype in this disease. Worldwide, there are greater than 60,000 new cases of NPC reported per year, and in southern China, the incidence of NPC is 25-30 per 100,000 persons per year. The majority of patients with NPC present with advanced disease and the prognosis for these individuals is especially poor despite treatment with chemotherapy and/or radiation therapy. The EBV encoded nuclear antigen 1 (EBNA1) is an episomal replication factor that is required for maintenance of the viral genomic episome in EBV infected tissues. EBNA1 has also been shown to have tumorgenic and anti-apoptotic properties. In this application, we propose the development of small interfering RNAs (siRNAs) which specifically target the EBNA1 mRNA as a potential therapeutic approach for NPCs. Being mechanistically distinct from existing therapeutics; this approach represents a previously unexplored avenue of investigation and may have potential especially in combination with chemotherapy or radiation regimens. This work is exploratory in nature and we are therefore submitting this application through the R21 mechanism with the goal of establishing a "proof of principle" for this approach.

描述（由申请人提供）：EB病毒（EBV）与鼻咽癌（NPC）密切相关，并在该疾病中肿瘤表型的发生和维持中发挥关键作用。全球范围内，每年报告的鼻咽癌新病例超过 60,000 例，在中国南方，鼻咽癌的发病率为每年每 10 万人中 25-30 例。大多数鼻咽癌患者都患有晚期疾病，尽管接受化疗和/或放射治疗，但这些患者的预后特别差。 EBV 编码的核抗原 1 (EBNA1) 是一种附加型复制因子，是维持 EBV 感染组织中病毒基因组附加体所必需的。 EBNA1 还被证明具有致瘤和抗凋亡特性。在此应用中，我们建议开发专门针对 EBNA1 mRNA 的小干扰 RNA (siRNA)，作为 NPC 的潜在治疗方法。在机制上与现有疗法不同；这种方法代表了一种以前未探索过的研究途径，尤其是与化疗或放疗方案相结合时可能具有潜力。这项工作本质上是探索性的，因此我们通过 R21 机制提交此申请，目的是为此方法建立“原理证明”。