Since its discovery in 1998 and winning the Nobel Prize in 2006, ribonucleic acid (RNA) interference has become an invaluable tool for drugmakers to silence disease-causing genes. Nearly three decades later, drug makers have developed six approved small interfering RNA (siRNA) therapeutics in the therapeutic areas of neurology, cardiovascular, endocrine, and metabolism, such as amyloidosis, familial amyloid polyneuropathies (FAPs), hyperlipidemia and other diseases. Delivery of siRNA therapeutics to a variety of tissues and cells of interest has remained a major challenge for the application of siRNA therapeutics in humans.
The current state of the art is N-acetylgalactosamine siRNA conjugates (GalNAc-siRNA), which deliver exclusively to the liver, limiting the number of diseases that can be treated. Developing RNA conjugational approaches for targeting extra-hepatic tissues is the ultimate goal for RNA therapeutics delivery. In a recent Molecular Therapy publication by Vikas Kumar and colleagues titled "Efficient and selective kidney targeting by chemically modified carbohydrate conjugates," Raman Bahal's team at UConn School of Pharmacy Department of Pharmaceutical demonstrates the development of a novel kidney-targeted delivery platform called RENTAC-Renal Tubule Targeting Carbohydrate.
RENTAC targets the kidney via the megalin receptor family—an endogenous cell-surface receptor family expressed at high levels on the apical side of proximal tubule epithelial cells (PTECs.