RNA Silencing in the Oral Cavity

口腔中的 RNA 沉默

• 批准号: 7670493
• 负责人: Andrew George Jakymiw
• 金额: $ 9.72万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7670493
• 关键词: Abbreviations; Address; Animal Model; Apoptosis; Award; Biological; Biological Process; Cancer cell line; Cell physiology; Cells; Clinical; Clinical Trials; Communicable Diseases; Dentistry; Dependovirus; Disease; Drug Design; Effectiveness; Eye; Florida; Functional RNA; Gene Silencing; Gene Targeting; Genes; Goals; Head and Neck Squamous Cell Carcinoma; Human; Immunoprecipitation; In Vitro; Indirect Immunofluorescence; Infectious Lung Disorder; Investigation; Laboratories; Lamin Type A; Link; Lung; Macular degeneration; Measures; Mediating; Mentors; Methods; MicroRNAs; Molecular; Mouth Diseases; Muscle; Neurodegenerative Disorders; Nuclear Envelope; Oncogenes; Oral Medicine; Oral cavity; Oral health; Oral mucous membrane structure; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Principal Investigator; Process; Proteins; Publishing; Pyroxylin; RNA Interference; RNA-Induced Silencing Complex; Recombinants; Reporter; Reporting; Research; Research Personnel; Role; Scientist; Skin; Small Interfering RNA; Staging; Subcellular structure; Techniques; Testing; Therapeutic; Tissues; Training; Transgenic Organisms; Translating; Universities; Use Effectiveness; Vagina; anticancer research; base; cancer cell; career; cell growth; college; effective therapy; enhanced green fluorescent protein; env Gene Products; gene function; gene therapy; improved; in vivo; inhibitor/antagonist; mRNA Decay; malignant mouth neoplasm; mouse model; new technology; novel therapeutic intervention; oral biology; oral tissue; red fluorescent protein; small hairpin RNA; subcutaneous; tissue culture; tumor; tumor xenograft; viral gene delivery

DESCRIPTION (provided by applicant): Recently, our laboratory has demonstrated that cytoplasmic foci termed GW bodies (GWBs) for the GW182 protein they harbor are linked to an evolutionarily conserved mechanism involved in the post-transcriptional silencing of genes, referred to as RNA interference (RNAi). RNAi is a cellular process that is revolutionizing gene function studies and there is considerable excitement about using RNAi for therapy. Currently, our lab is focused on furthering the biological study of GW182 and GWB function, with the goal to ascertain the role of GWBs in the activation of the RNAi process and their contribution to regulating off-target effects. By furthering our understanding of the biological functions of GWBs, this should translate into improved drug designs for RNAi-based treatments. Despite the growing number of reports demonstrating the many exciting therapeutic aspects of RNAi, only a limited number of articles have been published regarding the application of RNAi in the treatment of oral diseases. It is therefore, the P.l.'s immediate goal to address this concern by bringing RNAi-based treatments to oral medicine during his transition from a mentored stage to becoming an independent scientific investigator. The long-term career objective is to establish himself as an expert in the field of oral health and RNAi-based therapies. A major advantage is that the oral mucosa is readily accessible to manipulation and may be especially suitable for RNAi-based treatments. It is therefore the principal investigator's plan to further his training in the field of oral biology at the University of Florida College of Dentistry, in particular in the field of oral cancer research. During the mentored phase of the award the principal investigator will characterize RNAi function in oral cancer cells, and optimize drug and viral gene delivery techniques in vitro and in vivo. Furthermore, the principal investigator will identify and target potential cancer-promoting gene targets in vitro using RNAi. During the independent phase of the award the principal investigator proposes to detemine the feasability of using RNAi-based drug and gene therapy approaches to treat a human tumor mouse model. The long-term research goal of this proposal is to exploit this novel technology and develop it into an effective therapy for oral cancer. By harnessing RNAi for oral medicine it will allow both scientists and clinicians to silence diseases of the oral cavity. Results from our proposed studies may have a broader impact applicable to treatment of other diseases using RNAi-based therapies.

描述（由申请人提供）：最近，我们的实验室证明，它们所携带的 GW182 蛋白被称为 GW 体 (GWB) 的细胞质灶与参与基因转录后沉默的进化保守机制（称为 RNA 干扰）有关。 （RNAi）。 RNAi 是一种细胞过程，正在彻底改变基因功能研究，并且使用 RNAi 进行治疗令人非常兴奋。目前，我们实验室正致力于进一步深入GW182和GWB功能的生物学研究，旨在确定GWB在RNAi过程激活中的作用及其对调节脱靶效应的贡献。通过进一步了解 GWB 的生物学功能，这应该转化为基于 RNAi 的治疗的改进药物设计。尽管越来越多的报告证明了 RNAi 的许多令人兴奋的治疗方面，但关于 RNAi 在口腔疾病治疗中的应用发表的文章数量有限。因此，P.l. 在从指导阶段过渡到成为独立科学研究人员期间，近期目标是通过将基于 RNAi 的治疗方法引入口腔医学来解决这一问题。长期职业目标是使自己成为口腔健康和 RNAi 疗法领域的专家。一个主要优点是口腔粘膜易于操作，并且可能特别适合基于 RNAi 的治疗。因此，首席研究员计划在佛罗里达大学牙科学院进一步接受口腔生物学领域的培训，特别是口腔癌研究领域的培训。在该奖项的指导阶段，主要研究者将表征口腔癌细胞中的 RNAi 功能，并优化体外和体内药物和病毒基因传递技术。此外，主要研究人员将利用 RNAi 在体外识别和靶向潜在的促癌基因靶标。在该奖项的独立阶段，主要研究者建议确定使用基于 RNAi 的药物和基因治疗方法治疗人类肿瘤小鼠模型的可行性。该提案的长期研究目标是利用这项新技术并将其发展为口腔癌的有效疗法。通过将 RNAi 用于口腔医学，科学家和临床医生将能够抑制口腔疾病。我们提出的研究结果可能会产生更广泛的影响，适用于使用基于 RNAi 的疗法治疗其他疾病。