Using natural pathways to silence disease-causing genes.
Dicerna discovers and develops drugs designed to silence or “knock down” the expression of a targeted gene in a way that is highly selective, specific, precise and reversible.
Our drugs harness the power of the natural RNA interference (RNAi) pathway, a pathway within cells whose purpose is to silence genes. In this biological process, the double-stranded RNA molecules trigger the potent and specific destruction of messenger RNAs (mRNAs) of disease-driving genes.
We invented the RNAi technology platform called GalXCTM, which is a proprietary technology platform that advances the development of next-generation RNAi-based therapies designed to silence disease-driving genes in the liver. GalXC-based therapies are processed by the Dicer enzyme, which is the natural initiation point for RNAi within the human cell. By using the Dicer enzyme as the entry point into the RNAi, we seek to optimize the activity of the RNAi pathway so that it operates in the most specific and potent fashion. Compounds produced via GalXC are intended to be broadly applicable across multiple therapeutic areas, including rare diseases, viral infectious diseases, chronic liver diseases, and cardiovascular diseases.
Dr. Douglas Fambrough, president and chief executive office, and Bob Brown, chief scientific officer and senior vice president of research and development, provide an overview of Dicerna’s GalXC technology and how it is differentiated.
Dicerna’s RNAi technology reflects a new approach in the development of therapies to treat diseases involving the liver such as rare diseases, viral infectious diseases, chronic liver diseases, and cardiovascular diseases.
The GalXC RNAi technology platform is particularly well-suited for subcutaneous delivery of RNAi therapies to the liver, as hepatocytes (a type of liver cell) have a cell surface membrane receptor for the GalNAc sugars that are attached to GalXC compounds. This leads to effective internalization and access to the RNAi machinery within hepatocytes.
RNAi therapy is considered a rational approach to treating liver diseases such as primary hyperoxaluria , a severe, rare, genetic disease in which a single gene error in liver metabolism leads to high levels of oxalate in the urine, resulting in progressive and severe damage to the kidneys and other organs. RNAi may also emerge as a viable treatment for chronic liver diseases such as nonalcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), autoimmune hepatitis (AIH) and progressive familial intrahepatic cholestasis (PFIC).
Although GalXC compounds have a remarkable affinity for hepatocytes, the potential utility of GalXC-derived RNAi therapy is not limited to diseases of the liver. Indeed, Dicerna has qualified dozens of disease-associated genes in clinical indications where we believe an RNAi-based inhibitor may provide substantial benefit to patients, providing expansive therapeutic opportunities. In addition, Dicerna has developed hits and/or optimized GalXC conjugate inhibitors against dozens of these qualified targets. These genetic targets span the therapeutic areas of rare diseases, viral infectious diseases, chronic liver diseases, and cardiovascular diseases. The common thread among these targets is the expression of disease-associated genes in the liver. By silencing these genes, GalXC-based RNAi therapy may thus prove to be a valuable and practical therapeutic approach for a wide range of diseases.