RNA Silencing in the Oral Cavity

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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.