Abstract 289: Non-viral Rna Delivery To The Endothelium
Dysfunctional vasculature contributes to more disease than any other tissue in the body1. Small interfering RNAs (siRNAs) have the potential to help elucidate the role of endothelial cells in vivo by durably silencing multiple genes simultaneously, but this requires efficient delivery, which has remained challenging in cell types besides hepatocytes. We have developed nanoparticles that deliver siRNA to endothelial cells with high specificity, thereby facilitating the silencing of multiple endothelial cell genes in vivo. These particles do not significantly reduce gene expression in hepatocytes or immune cells even at doses forty times greater than those required for endothelial gene silencing. Optimized formulations achieved the most durable non-liver silencing reported to date, and delivered siRNAs that modified endothelial function in mouse models of vascular permeability, emphysema, primary tumor growth, and metastasis. We believe the nanomaterial described here may improve the ability to study endothelial gene function in vivo, and be used to treat diseases caused by vascular dysfunction.
- © 2013 by American Heart Association, Inc.