Glossary of key terms
Alpha-1 antitrypsin (A1AT) deficiency
Alpha-1 antitrypsin (A1AT) deficiency is an inherited disorder that can lead to liver disease in children and adults and lung disease in adults.
The complement system is a part of the immune system that enhances, or complements, the ability of antibodies to clear small organisms or damaged cells from an organism, promote inflammation and attack the pathogen’s cell membrane.
DCR-A1AT is an investigational drug in development by Dicerna for the treatment of alpha-1 antitrypsin (A1AT) deficiency.
DCR-HBVS is an investigational drug in development by Dicerna and Roche for the treatment of chronic hepatitis B virus (HBV) infection.
Deoxyribonucleic acid (DNA)
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. RNA is a molecule that plays a role in how genes control the building of proteins. Messenger RNA (mRNA) is a type of RNA that translates the instructions contained within DNA. This mRNA is the target of RNAi.
GalXC is our proprietary RNAi technology platform that advances the development of next-generation RNAi-based therapies designed to silence disease-driving genes. GalXC molecules can be administered subcutaneously in an infrequent dosing regimen, which has the potential to reduce treatment burden for patients.
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.
Hepatitis B virus surface antigen (HBsAg)
HBsAg is a protein on the surface of a virus that causes the immune system to make antibodies. The ability for a drug to provide a long-term functional cure of HBV is measured in part through the clearance of HBsAg.
Hepatitis B virus (HBV)
Hepatitis B is a liver infection caused by the hepatitis B virus (HBV). HBV is transmitted when blood or another body fluid from a person infected with HBV enters the body of someone who is not infected.
Lactate dehydrogenase A (LDHA)
LDHA is an enzyme which is encoded by the LDHA gene in humans. Silencing the LDHA gene in the liver with RNAi may be beneficial for patients with PH, as the LDHA enzyme is implicated in the abnormal production of oxalate in patients with PH. This abnormal production of oxalate is responsible for the severe damage to kidneys and other organs in patients with PH.
Messenger RNA (mRNA)
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 building of a protein. mRNA is targeted by the RNAi machinery.
Nedosiran is an investigational drug in development by Dicerna and is the only treatment in development for all three known genetic types of primary hyperoxaluria (PH). It is the most advanced product candidate utilizing our GalXC™ technology.
Nonalcoholic steatohepatitis (NASH)
Nonalcoholic steatohepatitis (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)
Primary hyperoxaluria (PH) is a family of ultra-rare, life-threatening genetic disorders that cause complications in the kidneys. There are three known genetic types of PH, each resulting from a mutation in one of three different genes. These genetic mutations cause enzyme deficiencies that manifest in the overproduction of a substrate called oxalate. Abnormal production and accumulation of oxalate leads to recurrent kidney stones, nephrocalcinosis and chronic kidney disease that may progress to end stage renal disease requiring regular dialysis and a dual liver-kidney transplant.
Ribonucleic acid (RNA)
RNA 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 natural process that occurs within the human body at the molecular level. Its function is to silence, or “turn off,” specific genes that cause disease.
Small-interfering RNAs (siRNAs)
Small-interfering RNAs (siRNAs) target and destroy the mRNAs that create defective or misregulated proteins that drive disease. GalXC molecules are Dicerna’s proprietary form of siRNAs.
The tetraloop configuration, which is unique to Dicerna’s GalXC compounds, serves as the attachment point for agents that target GalXC molecules to different tissues.