Glossary of Key Terms
Alpha-1 antitrypsin (A1AT)
Alpha-1 antitrypsin deficiency is an inherited disorder that may cause lung disease and liver disease. The signs and symptoms of the condition and the age at which they appear vary among individuals.
Dicer is an enzyme that plays a key role in RNAi. When double-stranded RNA enters a cell, the cell identifies it as foreign RNA (for example, RNA from a virus) and activates a defense mechanism to target and degrade all sequences that are similar to the foreign RNA. Dicer is central to this process – it binds to the double-stranded RNA and initiates the RNAi pathway which destroys the RNA.
Deoxyribonucleic acid, or DNA, is the genetic material: our genes reside in our DNA. Long strings of DNA bases spell out a code for making the proteins that make up our cells and tissues, such as muscle and blood. DNA acts as a repository of genetic information. For the information to be used, an mRNA copy of the DNA must be made first. This mRNA is the target of RNAi.
GalXCTM is our proprietary RNAi technology platform that advances the development of next-generation RNAi-based therapies designed to silence disease-driving genes in the liver. GalXC molecules can be administered subcutaneously in an infrequent dosing regimen.
Genes are strings of DNA that serve as the functional and physical unit of heredity passed from parent to offspring. Most genes contain the information for making a specific protein. When mutated or inappropriately activated, certain genes can drive diseases, including cancer.
Hepatitis B Virus (HBV)
Hepatitis B is a liver infection caused by the Hepatitis B virus (HBV). Hepatitis B is transmitted when blood, semen, or another body fluid from a person infected with the Hepatitis B virus enters the body of someone who is not infected.
KRAS is an oncogene this is frequently mutated in several common forms of cancer, including pancreatic, lung and colorectal cancers. KRAS encodes a small intracellular protein that has evaded the efforts of the pharmaceutical industry for decades, but that can be targeted with RNAi.
Messenger RNA (mRNA)
Messenger RNA (mRNA) is a single-stranded type of RNA that is made as a copy of the DNA sequence of a gene. mRNA carries the genetic instructions of that gene from the cell nucleus to the cytoplasm (the fluid inside the cell but outside of the nucleus, where most cellular chemical reactions take place). In the cytoplasm, the mRNA sequence is used to guide the assembly of a protein. mRNA is targeted by the RNAi machinery.
Nonalcoholic steatohepatitis (NASH)
NASH resembles alcoholic liver disease, but occurs in people who drink little or no alcohol. The major feature in NASH is fat in the liver, along with inflammation and damage. Most people with NASH feel well and are not aware that they have a liver problem. Nevertheless, NASH can be severe and can lead to cirrhosis, in which the liver is permanently damaged and scarred and no longer able to work properly.
Primary hyperoxaluria (PH) is a family of severe, rare, genetic liver disorders characterized by overproduction of oxalate, a natural chemical in the body that is normally eliminated as waste through the kidneys. In patients with PH, the kidneys are unable to eliminate the large amount of oxalate that is produced, and the accumulation of oxalate can result in severe damage to the kidneys and other organs.
Proprotein convertase subtilisin/kexin type 9 (PCSK9)
The PCSK9 gene provides instructions for making a protein that helps regulate the amount of cholesterol in the bloodstream. The PCSK9 protein appears to control the number of low-density lipoprotein receptors, which are proteins on the surface of cells. These receptors play a critical role in regulating blood cholesterol levels.
RNA, which stands for ribonucleic acid, is a genetic material with diverse uses within the cell. Most notably, when a gene is being used, a copy of its DNA sequence is made using RNA. This RNA copy is known as messenger RNA, or mRNA. The RNAi machinery targets mRNA.
RNA interference (RNAi)
RNAi is a biologic process in which certain double-stranded RNA molecules inhibit the expression of disease-causing genes by destroying the messenger RNAs (mRNAs) of those genes.
The tetraloop is a folded motif incorporated within the extended region of conjugates produced via Dicerna’s GalXC technology. The tetraloop configuration, which is unique to Dicerna’s GalXC compounds, interfaces effectively with the RNAi machinery.
*Denotes this is a Dicerna proprietary technology