Small Molecule Targeting of Viral Non-Coding RNA EBER1 to Detect and Treat Latent EBV

小分子靶向病毒非编码 RNA EBER1 检测和治疗潜伏 EBV

• 批准号: 9764252
• 负责人: Ursula D Ramirez
• 金额: $ 30万
• 依托单位: VIRONIKA, LLC
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9764252
• 关键词: Address; African Burkitt' s lymphoma; Animal Model; Autoimmune Diseases; Binding; Biochemical; Biological Assay; Biopsy; Biotechnology; Carcinoma; Cell Proliferation; Cell Survival; Cells; Chemicals; Chronic; Clinical Trials; Collaborations; Detection; Development; Disease; Drug Kinetics; Epstein-Barr Virus Infections; Epstein-Barr Virus latency; Epstein-Barr virus encoded RNA 1; Fluorescence Polarization; Foxes; Goals; Hodgkin Disease; Human; Human Herpesvirus 4; Image; Immune System Diseases; Infectious Mononucleosis; Inflammatory Response; Latent virus infection phase; Lead; Legal patent; Libraries; Luciferases; Lymphoma; Lymphomagenesis; Lymphoproliferative Disorders; Malignant Neoplasms; Measures; Medical; Messenger RNA; Methods; Molecular Analysis; Monitor; Multiple Sclerosis; Nasopharyngeal Undifferentiated Carcinoma; Non-Hodgkin' s Lymphoma; Nuclear; Nuclear Antigens; Oncogenic Viruses; Pharmaceutical Chemistry; Pharmacodynamics; Phase; Primary Infection; Property; Proteins; Quantitative Structure-Activity Relationship; RNA; Reporter; Ribosomes; Seeds; Signal Pathway; Site; Small Business Innovation Research Grant; Small Nuclear RNA; Stomach Carcinoma; Structure; Surface Plasmon Resonance; T-Cell Lymphoma; Telomerase; The Wistar Institute; Therapeutic; Therapeutic Intervention; Trust; Tumorigenicity; United States Food and Drug Administration; Untranslated RNA; Viral; Virus Diseases; base; cell growth; drug candidate; first-in-human; imaging probe; inhibitor/antagonist; latent infection; meetings; mouse model; novel; off-patent; post-transplant; programs; screening; small molecule; small molecule inhibitor; tumor; tumorigenesis

Summary The goal of this SBIR program is to develop novel small molecule probes and inhibitors targeting a viral non-coding RNA expressed at high levels in all forms of Epstein-Barr Virus (EBV) tumors. EBER1 is a highly conserved, viral-encoded small nuclear RNA expressed consistently at high-levels in all EBV tumors. EBER1 is required for EBV tumorigenesis in mouse models and functionally interacts with ribosomal subunit L22 that has been implicated in the telomerase immortalization and TLR signaling pathways. The project addresses an unmet medical need to detect and treat EBV- associated cancers and related diseases. EBV latent infection is a causal factor in undifferentiated nasopharyngeal carcinoma, endemic Burkitt’s lymphoma, 50% of Hodgkin’s lymphomas, 20% of non-Hodgkin’s lymphomas, NK/T cell lymphoma, 10% of gastric carcinomas, and the majority of post-transplant lymphoproliferative disease. EBV primary infection is the major cause of infectious mononucleosis. EBV infection is also implicated as a causal agent of multiple sclerosis. To date, no viral-specific therapeutic exists for treatment of EBV latent infection, nor are there non-invasive methods to detect EBV latent infection in tumors. EBER1 is among the most abundant and stable nuclear non-coding RNAs expressed exclusively in EBV positive tumors and therefore represents an ideal target for detection and treatment of EBV-specific tumors. We propose to develop novel and safe small molecules that can selectively bind EBER1 and inhibit its interaction with L22. The product that ultimately results from this proposal is a small molecule probe that selectively binds EBER1 RNA, and can be further developed for the detection and treatment of EBV malignancies and associated diseases.

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