Anastasiia Vasylaki
Kidney-Targeting Nanomedicine for siRNA Delivery in Chronic Kidney Disease
Abstract
Chronic kidney disease (CKD) is a growing healthcare burden affecting 1 in 7 US adults. CKD has close links to hypertension, which is both a cause and a consequence of kidney dysfunction. We have identified NF-kB as a promising therapeutic target in hypertensive CKD since this transcription factor modulates several pathophysiological pathways involved in CKD progression. We propose to deliver siRNA against NF-kB specifically to tubular epithelial cells using mesoscale lipid nanoparticles (MLNPs), which target the kidneys based on their size in the 300 – 500 nm range and a PEGylated surface. Preliminary data on the MLNP formulation demonstrates superior kidney selectivity (24-fold higher kidney vs. liver accumulation). In the proposed work, we aim to further investigate the pharmacokinetics and biodistribution of siRNA MLNPs and evaluate their therapeutic efficacy in a Dahl salt-sensitive rat model of hypertensive CKD.
I am very honored to receive the PhRMA Foundation Fellowship. This award reaffirms my confidence that our research on kidney-targeting nanomedicines is moving in the right direction, and we are on track to develop novel kidney disease therapies.
