SiRNA Therapy for Glomerulonephritis

Abstract

We are well into a new era in pharmacology in which small molecules, often kinase inhibitors, are used to target signal transduction pathways in cancer and other diseases. In addition to small molecules, antibody-based treatments have become a major part of the pharmacologic armamentarium. RNA interference (RNAi)-based treatments promise to be a third pillar in this new frontier. Indeed, several biotech firms have been established in the past decade to develop RNAi-based therapies. In this issue of JASN , Shimizu et al. 1 bring RNAi-based therapies to bear on kidney disease by demonstrating that small interfering RNAs (siRNAs) to a mitogen-activated protein kinase (MAPK) prevent glomerular disease in a murine model of lupus nephritis. siRNAs are short, double-stranded RNAi molecules that contain complementary sequences to specific mRNAs encoding proteins. By interacting with mRNAs through these complementary sequences, they act similarly to naturally occurring microRNAs to cause degradation of the mRNA or to inhibit translation.2 Interruption of microRNA processing causes dramatic glomerulotubular …