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Lecture Juliane Nguyen


18 September 2012 FWN-Building 5116.0136, Nijenborgh 4, 9747 AG, Groningen
Speaker: Dr. Juliane Nguyen
Affiliation: University of California San Francisco (UCSF), Department of Bioengineering & Therapeutic Sciences
Title: The silent treatment of genes: Degradable polymers and bioresponsive lipids for siRNA delivery
Date: Tue Sep 18, 2012
Start: 09.00
Location: FWN-Building 5118.0161
Host: T.T.M. Palstra
Telephone: +31 50 363 4419


The delivery of RNA interference (RNAi) agents can alter the expression of virtually any protein in a cell. As such, this process opens the path for cures to most diseases that afflict humans. However, nucleic acids have high molecular weights, an anionic nature, and are unstable in the presence of enzymes, all of which inhibit their delivery. Thus, vehicles capable of efficiently delivering nucleic acids are still needed. In this seminar I will show how the material properties of nanocarriers can be modulated to optimize their assembly and disassembly during siRNA delivery using two different nanocarrier platforms. The first platform is polymeric and is based on high molecular weight PLGA-grafted amine-modified polyvinyl alcohol (DEAPA-PVA-PLGA) that disassembles into smaller fragments by amine-catalyzed hydrolysis. These polymers allow for the controlled release of siRNA with tunable degradation and release kinetics. These kinetics can be controlled by changing the PLGA chain lengths and by modulating the amine density. The second platform assembles from ionizable lipids that can undergo a charge conversion from negative to positive when exposed to acidic pH. The lipid systems are activated within cells when exposed to the low pH of the endosomal compartments where they release their siRNA content and transfer them into the cytoplasm. These systems do not induce the secretion of cytokines or chemokines after intravenous administration in mice. Hence, they are potential alternatives to the cationic lipids that are currently used for gene and siRNA delivery in animals and humans.

Last modified:22 October 2012 2.30 p.m.