RNA Silencing in the Oral Cavity

口腔中的 RNA 沉默

• 批准号: 7531996
• 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/7531996
• 关键词: Abbreviations; Address; Animal Model; Apoptosis; Award; Biological; Biological Process; Cancer cell line; Cell physiology; Cells; Clinical; Clinical Trials; Communicable Diseases; DAPI; 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; Messenger RNA; Methods; MicroRNAs; Molecular; Mouth Diseases; Muscle; Neurodegenerative Disorders; Nuclear Envelope; Numbers; Oncogenes; Oral Medicine; Oral cavity; Oral health; Oral mucous membrane structure; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Principal Investigator; Process; Proteins; Publishing; Pyroxylin; RNA Decay; 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; day; enhanced green fluorescent protein; env Gene Products; gene function; gene therapy; improved; in vivo; inhibitor/antagonist; malignant mouth neoplasm; mouse model; new technology; novel therapeutics; 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，我们的实验室证明了它们所携带的GW182蛋白的细胞质灶称为GW身体（GWB），与参与基因转录后的进化机制有关，被称为RNA干扰（RNAI）。 RNAi是一种彻底改变基因功能研究的细胞过程，使用RNAi进行治疗引起了很大的兴奋。目前，我们的实验室重点是进一步发展GW182和GWB功能的生物学研究，目的是确定GWB在RNAi过程激活中的作用及其在调节脱靶效应方面的贡献。通过进一步了解GWBS的生物学功能，这应该转化为改进基于RNAi的治疗的药物设计。尽管报告了越来越多的报告表明RNAi令人兴奋的治疗方面，但关于RNAi在口腔疾病治疗中的应用，仅发表了数量有限的文章。因此，P.L.的近期目标是通过将基于RNAi的治疗方法带到口腔医学中，从而在他从指导阶段过渡到成为独立的科学研究者。长期职业目标是确立自己的口腔健康和基于RNAi疗法领域的专家。一个主要的优点是口服粘膜很容易被操纵，并且可能特别适合基于RNAi的治疗方法。因此，主要研究者的计划是在佛罗里达大学牙科学院，特别是在口腔癌研究领域的口腔生物学领域进行培训。在奖励的指导阶段，主要研究者将表征口腔癌细胞中的RNAi功能，并在体外和体内优化药物和病毒基因递送技术。此外，主要研究者将使用RNAi在体外识别并靶向潜在的促进癌症基因靶标。在该奖项的独立阶段，主要研究者提议使用基于RNAi的药物和基因治疗方法来治疗人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，并将其发展为有效的口腔癌疗法。通过利用RNAi进行口腔医学，它将允许科学家和临床医生沉默口腔疾病。我们拟议的研究的结果可能具有更广泛的影响，可用于使用基于RNAi的疗法治疗其他疾病。