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In addition to its annual lectures, ChBE hosts a weekly seminar throughout the year with invited lecturers who are prominent in their fields. Unless otherwise noted, all seminars are held on Wednesdays in the Molecular Science and Engineering Building ("M" Building) in G011 (Cherry Logan Emerson Lecture Theater) at 4:00 p.m. Refreshments are served at 3:30 p.m. in the Emerson-Lewis Reception Salon.
Multiparametric evaluation of nanocarriers for siRNA delivery
An attractive feature of short interfering RNA (siRNA)-based therapies is the potential to silence the expression of any disease-related gene in a selective and sequence-dependent manner. This capacity to target any transcribed genomic sequence has already made siRNA-based approaches an invaluable tool in validating novel drug targets in cell-based disease models. siRNA molecules alone, however, are incapable of overcoming systemic and cellular barriers that prevent them from finding their targets. As a result, two major classes of formulations have emerged and are at various stages of development to achieve RNAi-based therapy: lipid- and polymer-based nanocarriers. In this talk, I will provide a detailed look at representative members in each of these classes, with an emphasis on the complexity of the barriers that need to be overcome both in vitro and in vivo. With regards to polymeric nanocarriers, I will discuss the delivery of siRNAs and gene inhibition via RNAi in humans using systemically administered cyclodextrin-based nanocarriers. With regards to lipid-based nanocarriers, I will introduce a new synthetic route for lipid synthesis and discuss how multi-parametric evaluation of biophysical and cellular properties can improve in vitro-in vivo translation and structure-activity-relationships. Overall, the development of successful future delivery platforms will rest upon the discovery and understanding of new biological barriers as well as the design of new molecular components that can bypass and/or address these barriers.