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Glossary Glossary

Glossary

AAT

A condition that is caused by mutations in the alpha-1 antitrypsin gene. Mutations in this gene cause the lungs and liver and lungs to be prone to disease. Also known as Alpha-1 Antitrypsin Deficiency.


Acute Intermittent Porphyria

A very rare genetic disorder caused by an inherited deficiency in porphobilinogen deaminase that can result in accumulation of toxic intermediates in the heme biosynthesis pathway. Also known as AIP.


aHUS

A disease that primarily affects kidney function by causing abnormal blood clots to form in small blood vessels in the kidneys. Atypical hemolytic-uremic syndrome is characterized by three major related to abnormal blood clotting: hemolytic anemia, thrombocytopenia, and kidney failure. Also known as atypical hemolytic-uremic syndrome.


AIP

A very rare genetic disorder caused by an inherited deficiency in porphobilinogen deaminase that can result in accumulation of toxic intermediates in the heme biosynthesis pathway. Also known as acute intermittent porphyria.


ALN-AAT

An RNAi therapeutic developed by Alnylam that targets the enzyme alpha-1 antitrypsin efficiency (AAT) for the treatment of liver disease.


ALN-AS1

An RNAi therapeutic developed by Alnylam that targets the gene aminolevulinate synthase-1 (ALAS-1) for the treatment of acute intermittent porphyria (AIP).


ALN-AT3

An RNAi therapeutic developed by Alnylam that targets the gene antithrombin (AT) in an effort to diminish the effects of hemophilia and other bleeding disorders.


ALN – CC5

An RNAi therapeutic developed by Alnylam the serves as a treatment for complement-mediated diseases. More specifically, ALN-CC5 targets the C5 component of the complement system, which plays a large role in regulating the immune system. A loss of function in complement component C5 can lead to life-threatening cases of certain diseases such as paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic-uremic syndrome (aHUS).


ALN-PCS

An RNAi therapeutic developed by Alnylam that targets the gene proprotein convertase subtilisn/kexin type 9 (PCSK9) for the treatment of severe hypercholesterolemia.


ALN-TMP

An RNAi therapeutic developed by Alnylam that targets transmembrane protease serine 6 (Tmpss6) for the treatment of hemoglobinopathies and other iron-related diseases such as beta-thalassemia and sickle cell anemia. Hemoglobinopathies are associated with chronic anemia, extra-medullary hematopoiesis, and iron overload.


ALN-TTR

An RNAi therapeutic program developed by Alnylam that targets the treatment of TTR- mediated amyloidosis (ATTR) by silencing the expression of mutated TTR genes in patients.


ALN-TTR02

An RNAi therapeutic that is part of Alnylam’s ALN-TTR program. It is designed specifically for the treatment of patients with familial amyloidic polyneuropathy (FAP).


ALN-TTRsc

A subcutaneously administered RNAi therapeutic that is part of Alnylam’s ALN-TTR program. It is designed specifically for the treatment of patients with familial amyloidic cardiomyopathy (FAC)


Alnylam 5×15

A program developed by Alnylam in 2011 that revolves around the idea of the company having five RNAi therapeutics that target diseases with high unmet medical need by the year 2015. These therapeutics are AALN-TTR, a therapeutic designed for the treatment of TTR-mediated amyloidosis (ATTR), ALN-AT3, a therapeutic designed for the treatment of hemophelia and rare bleeding disorders, ALN-AS1, a therapeutic designed for the treatment of of acute intermittent porphyria (AIP), ALN-PCS a therapeutic designed for the treatment of severe hypercholesterolemia, ALN-TMP, a therapeutic designed for the treatment of hemoglobinopathies and iron-related diseases, and ALN-CC5, a therapeutic designed for the treatment of complement-mediated diseases.


Alpha-1 Antitrypsin Deficiency

A condition that is caused by mutations in the alpha-1 antithypsin gene. Mutations in this gene cause the lungs and liver and lungs to be prone to disease. Also known as AAT.


Antisense technology

Oligonucleotides designed to bind target RNAs (e.g. mRNA, microRNA, etc.) based on sequence complementarity in order to block their natural function. Antisense technology can also describe a general approach that includes RNAi and siRNAs.


Antithrombin

Also known as AT, antithrombin is a liver-expressed plasma protein that acts as an important endogenous anticoagulant by inactivating factors Xa and thrombin. AT also plays a key role in maintaining normal hemostasis, which controls the clotting of blood.


Asialoglycoprotein Receptor

Also known as ASGPR, the asialogycoprotein receptor is one of the most abundant cell receptors on the surface of hepatocytes


ASGPR

Also known as the asialoglycoprotein receptor, ASGPR is one of the most abundant cell receptors on the surface of hepatocytes


AT

Also known as antithrombin, AT is a liver-expressed plasma protein that acts as an important endogenous anticoagulant by inactivating factors Xa and thrombin. AT also plays a key role in maintaining normal hemostasis, which controls the clotting of blood.


ATTR

Also known as transthyretin-mediated amyloidosis. A hereditary, systemic disease caused by a mutation in the transthyretin (TTR) gene. The mutation causes abnormal amyloid proteins to accumulate in and damage body organs and tissue such as the peripheral nerves and heart, resulting in neuropathic pain, autonomic neuropathy, and cardiomyopathy.


Atypical hemolytic-uremic syndrome

A disease that primarily affects kidney function by causing abnormal blood clots to form in small blood vessels in the kidneys. Atypical hemolytic-uremic syndrome is characterized by three major related to abnormal blood clotting: hemolytic anemia, thrombocytopenia, and kidney failure. Also known as aHUS.


Bioinformatics

Computational biology concerned with the management and analysis of biological data.


Canonical siRNA

Two strands of RNA, each 21 nucleotides long with a central region of complementarity that is 19 base-pairs long for the formation of dsRNA and two nucleotide overhangs at each of the 3_ ends.


Conjugation

The addition of chemical groups to an active drug ingredient with the aim of improving drug performance.


Central Nervous System

Comprised of the brain and spinal cord, the central nervous system is responsible for processing information sent from the body’s nervous system. More specifically, the brain processes and interprets sensory information sent from the spinal cord, which then gets sent to specific parts of the body. Functions affected by the central nervous system include muscle control, eyesight, breathing and memory. Also known as the CNS.


Compliment Component C5

A protein that plays an important role in keeping the immune system healthy by killing bacteria cells and regulating inflammation. Mutations in this protein lead to compliment component 5 deficiency, a disease where patients show a propensity for severe recurrent infections.


CNS

Comprised of the brain and spinal cord, the CNS is responsible for processing information sent from the body’s nervous system. More specifically, the brain processes and interprets sensory information sent from the spinal cord, which then gets sent to specific parts of the body. Functions affected by the CNS include muscle control, eyesight, breathing and memory. Also known as the central nervous system.


Dicer

Central enzyme in the natural RNAi pathway that generates the active small RNAs by cleaving dsRNA precursors.


DNA

Deoxyribonucleic acid; genetic material consisting of any sequence of deoxyribonucleotides containing bases of adenine (A), thymine (T), guanine (G), and cytosine (C).


dsRNA

Double-stranded RNA; matching of a chain of ribonucleic acid, RNA, by a complementary strand of RNA. In this conformation, an adenine nucleotide present in one strand bonds, or base-pairs, with a uracil nucleotide on the complementary strand, and a guanine nucleotide to a cytosine.


Enzyme

A substance produced in an organism that acts as a catalyst, or chemical accelerator, to facilitate a specific biochemical reaction.


Familial Amyloidic Cardiomyopathy

A life-threatening disorder in which mutated transthyretin proteins cause abnormal heart function. Also known as FAC.


FAC

A life-threatening disorder in which mutated transthyretin proteins cause abnormal heart function. Also known as familial amyloidic cardiomyopathy.


Familial Amyloidic Polyneuropathy

A life-threatening disorder in which nerve lesions are induced by deposits of amyloid fibrils, most commonly due to mutated transthyretin proteins.


FAP

A life-threatening disorder in which nerve lesions are induced by deposits of amyloid fibrils, most commonly due to mutated transthyretin proteins. Also known as familial amyloidic polyneuropathy.


Hemoglobin

The protein responsible for transporting oxygen throughout one’s blood.


Hemolytic anemia

Hemolytic anemia occurs when red blood cells break down prematurely and are destroyed faster than the body can replace them. This condition can lead to abnormally pale skin, yellowing of the eyes and skin, fatigue, shortness of breath, and rapid heart rate.


Hemophilia

Hemophilias are hereditary disorders caused by genetic deficiencies in various blood clotting factors, resulting in recurrent bleeds into joints, muscles, and other internal organs.


Hemophilia A

Hemophilia A is a type of hemophilia in which procoagulent factor VIII experiences a loss-of-function mutation, resulting in an imbalance of the hemostatic system and an excessive bleeding phenotype


Hemophilia B

Hemophilia B is a type of hemophilia in which procoagulent factor IX experiences a loss-of-function mutation, resulting in an imbalance of the hemostatic system and an excessive bleeding phenotype.


Hepatocyte

Hepatocytes are cells that make of the main tissue of the liver. These cells are responsible for protein storage, protein synthesis, transformation of carbohydrates, and the synthesis of cholesterol, bile salts and phospholipids.


Hepicidin

A hormone produced in the liver that is the master regulator of iron homeostasis.


High Density Lipoprotein (HDL)

Lipoprotein particle in the blood. HDL is known as “good” cholesterol because it deposits cholesterol in the liver, where it is excreted by the body. High HDL is thought to protect against coronary artery disease.


Hypercholesterolemia

A condition characterized by very high levels of cholesterol in the blood. The body needs cholesterol to build cell membranes, make certain hormones, and produce compounds that aid in fat digestion. Too much cholesterol, however, increases a person’s risk of developing heart disease.


Investigational New Drug (IND)

An application containing laboratory (pre-clinical) study results of a drug candidate is submitted to the FDA to request permission to conduct studies in humans.


Gene

Basic genetic unit; DNA sequence that carries all the information for the functional production of a protein or non-coding RNA.


Genome

The entire DNA sequence of an organism.


Kinesin spindle protein (KSP)

Also known as “eglin 5_ or “Eg5_, is a protein required for cell division that, when inhibited, leads to cell arrest and cell death in dividing cells.


LDL cholesterol

Otherwise known as the “bad” cholesterol, LDLc is the cholesterol that is found in low-density lipoproteins. This type of cholesterol is bad for a number of reasons, a few of them being that they cause inflammation , and can collect with white blood cells to create a plaques that block arteries, and can lead to coronary artery disease. Also known as LDLc


LDLc

Otherwise known as the “bad” cholesterol, LDLc is the cholesterol that is found in low-density lipoproteins. This type of cholesterol is bad for a number of reasons, a few of them being that they cause inflammation , and can collect with white blood cells to create a plaques that block arteries, and can lead to coronary artery disease. Also known as LDL cholesterol


Low Density Lipoprotein (LDL)

A lipoprotein particle in the blood responsible for depositing cholesterol into the lining of the artery. Known as “bad” cholesterol because high LDL is linked to coronary artery disease.


Monoclonal antibody

A single type of purified antibody derived from a clone of antibody-producing cells that can be generated in the laboratory and used for drug development where a therapeutic benefit is expected from the binding of the antibody to a protein target.


microRNA

Endogenous small RNAs, functionally related to siRNAs, involved in negatively regulating the expression of a large number of genes.


mRNA

Messenger RNA functioning as the template in protein translation. They are generated by the transcription of protein-coding genes.


Paroxysmal nocturnal hemoglobinuria

A rare, life-threatening disease caused by mutations in the PIGA gene that leads to impaired production of red and white blood cells as well as abnormal production of hemoglobin in urine. Also known as PNH.


PBGD

An enzyme found in the heme biosynthesis pathway that can result in the accumulation of toxic heme precursors. Mutations in this enzyme are responsible for causing Acute Intermittent Porphyria (AIP). Also known as porphobilinogen deaminase (PBGD).


PCSK9

A gene involved in the metabolism of low-density lipoprotein cholesterol (LDL-c, or “bad” cholesterol). A mutation in this gene results in a slower metabolism of LDL-c in humans, thus resulting in the development of hypercholesterolemia and other related diseases. Also known as proprotein convertase subtilism/kexin type 9.


Pharmacokinetics

Study on the absorption, distribution, metabolism, and elimination of a drug in the body over time.


Phase I clinical trial

The initial set of drug studies in humans, which are generally designed to evaluate the safety of a new drug in a small number of patients or normal volunteers.


Phase II

Controlled clinical studies conducted to evaluate the effectiveness of the drug for a particular indication or indications in patients with the disease or condition under study and to determine the common short-term side effects and risks.


Phase III clinical trial

These studies are the definitive trails conducted to demonstrate the safety and effectiveness of a new drug for the diagnosis or treatment of a disease.


PNH

A rare, life-threatening disease caused by mutations in the PIGA gene that leads to impaired production of red and white blood cells as well as abnormal production of hemoglobin in urine. Also known as Paroxysmal Nocturnal Hemoglobinuria


Porphobilinogen Deaminase

An enzyme found in the heme biosynthesis pathway that can result in the accumulation of toxic heme precursors. Mutations in this enzyme are responsible for causing Acute Intermittent Porphyria (AIP). Also known as PBGD


Porphyria

A set of diseases in which an important part of hemoglobin, called heme, is not properly made. As a result, patients develop neurological complications or skin problems.


Proprotein convertase subtilisn/kexin type 9

A gene involved in the metabolism of low-density lipoprotein cholesterol (LDL-c, or “bad” cholesterol). A mutation in this gene results in a slower metabolism of LDL-c in humans, thus resulting in the development of hypercholesterolemia and other related diseases. Also known as PCSK9


Protein

Amino acid chain generated following the translation of a mRNA. Proteins have a central structural, regulatory, and catalytic function in every living cell.


PSCK9

Proprotein convertase subtilisin/kexin type 9. The PCSK9 gene provides instructions for making a protein that helps regulate the amount of cholesterol in the bloodstream. Hypercholesterolemia is caused by mutations in the PCSK9 gene.


Pre-clinical

The testing of experimental drugs in the test tube or in animals before trials in humans may be carried out.


RiSC

RNA-induced silencing complex which when guided by an incorporated small RNA cleaves complementary target mRNA during RNAi.


RNA

Ribonucleic acid; genetic information consisting of any sequence of ribonucleotides containing bases of adenine (A), uracil (U), guanine (G), and cytosine (C).


RNAa

RNA activation, double-stranded RNAs that target promoter regions in chromosomal DNA resulting in transcriptional activation of genes. The transcriptional activation, or up-regulation, of genes results in an increase in mRNA and protein production.


RNAi

RNA interference, a natural cellular process where small interfering RNAs or microRNAs are used to control the normal expression of genes or are used to pharmacologically target disease-causing genes.


Respiratory syncytial virus (RSV)

A highly contagious virus that causes infections in both the upper and lower respiratory tract. RSV infects nearly every child at least once by the age of two years and is a major cause of hospitalization due to respiratory infection in children and people with compromised immune systems, and others.


shRNA

Small hairpin RNA expressed from a DNA template and processed into small RNAs to guide RNAi-mediated target mRNA degradation.


siRNA

Small interfering RNA. Optimally, two strands of RNA, each 19-25 nucleotides long with a central region of complementarity for the formation of dsRNA and optionally nucleotide overhangs at one or both of the the 3_ ends. siRNAs are the molecules that mediate RNAi. They are incorporated into RISC and used to form complementary pairing with a target mRNA, resulting in its enzymatic cleavage.


Small molecule

A small chemical, usually drug that due to its small size may be absorbed through the gut. Term often used in contrast to “large” protein therapeutics which have to be injected to bypass the gut.


Thrombocytopenia

Thrombocytopenia is characterized by a reduced level of circulating platelets, which are cell fragments that normally assist with blood clotting. This condition can cause abnormal bleeding and easy bruising.


Tmprss6

Otherwise known as transmembrane protease, this gene is responsible for the development of beta-thalassemia and iron-overload disorders. It functions by cleaving the protein hemojuvelin, resulting in elevated hepcidin levels and restricted iron mobilization.


Transmembrane protease

Otherwise known as Tmprss6, this gene is responsible for the development of beta-thalassemia and iron-overload disorders. It functions by cleaving the protein hemojuvelin, resulting in elevated hepcidin levels and restricted iron mobilization.


Transthyretin

Also known as TTR. A protein that is produced primarily in the liver and is normally a carrier retinol binding protein. Mutations in transhyretin cause abnormal amyloid proteins to accumulate in and damage body organs and tissue such as the peripheral nerves and heart, resulting in neuropathic pain, autonomic neuropathy, and cardiomyopathy.


Transthyretin-mediated amyloidosis

Also known as ATTR. A hereditary, systemic disease caused by a mutation in the transthyretin (TTR) gene. The mutation causes abnormal amyloid proteins to accumulate in and damage body organs and tissue such as the peripheral nerves and heart, resulting in neuropathic pain, autonomic neuropathy, and cardiomyopathy.


TTR amyloidosis

A hereditary, systemic disease caused by a mutation in the transthyretin (TTR) gene. The mutation causes abnormal amyloid proteins to accumulate in and damage body organs and tissue such as the peripheral nerves and heart, resulting in neuropathic pain, autonomic neuropathy, and cardiomyopathy.


TTR

Also known as transyretin. A protein that is produced primarily in the liver and is normally a carrier retinol binding protein. Mutations in the TTR gene cause abnormal amyloid proteins to accumulate in and damage body organs and tissue such as the peripheral nerves and heart, resulting in neuropathic pain, autonomic neuropathy, and cardiomyopathy.


Vascular endothelial growth factor (VEGF)

A protein that is secreted by oxygen-deprived cells, such as cancerous cells. VEGF stimulates new blood vessel formation, or angiogenesis, by binding to specific receptors on nearby blood vessels, encouraging new blood vessels to form.