NSTI BioNano 2010

Enhanced Endosomal siRNA Release from GeRPs Modulated by Membrane Permeabilizing Excipients

E.R. Soto, S. Kahlon, G.R. Ostroff
University of Massachusetts Medical School, US

Keywords: GeRPs, siRNA delivery, endosomal release

Abstract:

Glucan encapsulated siRNA Particles (GeRPs) have been recently shown to provide for efficient oral siRNA delivery (Aouadi et al., Nature 458; 1180. 2009). Microscopic imaging analysis of the release and intracellular distribution of fluorescent siRNA loaded GeRPs internalized by macrophages revealed that a significant proportion of the encapsulated siRNA remained associated in an endosomal compartment. To enhance endosomal release of siRNA into the cytoplasm we screened a variety of surfactants, endosomal swelling agents, and peptide excipients by microscopic image analysis. Generally agents effective at enhancing siRNA release into the cytoplasm enhanced gene silencing.
 
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