RNA Silencing in the Oral Cavity

描述（由申请人提供）：最近，我们的实验室已经证明，被称为GW体（GWB）的细胞质病灶（它们所携带的GW182蛋白）与涉及基因转录后沉默的进化保守机制（称为RNA干扰（RNAi））相关。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进行治疗相当令人兴奋。目前，我们的实验室专注于进一步研究GW182和GWB功能的生物学，目的是确定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治疗的改进药物设计。尽管有越来越多的报道证明了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的文章数量有限。因此，P.L.的直接目标是解决这一问题，在他从指导阶段过渡到成为一名独立的科学研究者期间，将基于RNAi的治疗方法引入口腔医学。长期的职业目标是将自己确立为口腔健康和基于RNAi疗法领域的专家。一个主要优点是口腔粘膜易于操作，并且可能特别适合于基于RNAi的治疗。因此，主要研究者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，主要研究者将描述RNAi在口腔癌细胞中的功能，并优化体外和体内的药物和病毒基因递送技术。此外，主要研究者将使用RNA干扰在体外识别并靶向潜在的促癌基因靶点。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种新技术，并将其发展为口腔癌的有效治疗方法。通过将RNAi用于口腔医学，它将使科学家和临床医生能够沉默口腔疾病。我们提出的研究结果可能对使用基于RNAi的疗法治疗其他疾病产生更广泛的影响。

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.