Small molecule-regulated gene silencing technologies

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CBET-0755053YokobaysahiIntellectual merit Since its recent discovery, RNA interference (RNAi) has emerged as a powerful tool for biologists to selectively repress expression of virtually any gene of their choice. RNAi has helped researchers to discover novel gene functions and how various genes interact, which are crucial to understanding the molecular basis of many biological processes and diseases. Additionally, numerous academic and industrial groups are intensively developing technologies to use RNAi to treat and cure diseases. Consequently, RNAi is expected to become an important technology for both basic science and applications. The goal of this project is to develop novel technologies to control when and where RNAi is induced by small molecule drugs. Chemically-regulated RNAi enables study of genes that are essential for cell survival or growth, observation of dynamic cellular functions, and increased safety for therapeutic applications. The presently available techniques, however, require coexpression of complex engineered protein(s), which can cause immunogenic complications or toxicity. The Principal Investigator's (PI's) proposed strategies harness the ability of RNA to specifically interact with a variety of compounds to engineer RNA to act as both a chemical sensor and RNAi inducer. The results are genetically small, protein-free, RNA nanomachines which sense specific signal molecules in the cell and decide whether or not to trigger RNAi. Broader impacts Although RNAi has quickly become a routine technique in many academic and industrial laboratories, students, especially undergraduate students, have very little opportunity to learn and practice the important technology. This project will allow a number of Biomedical Engineering students at UC Davis to gain hands-on experience with RNAi through the Senior Design course. The students will, in small groups, design novel chemically regulated RNAi systems, construct plasmid vectors to express them in mammalian cell lines, and study their functions over two academic quarters. Through this project, the students will gain valuable experience with RNAi and various bioengineering techniques in a team-oriented environment. Additionally, the research group will host one or two high school students per summer to engage in laboratory research through UC Davis Young Scholars Program.