A log to trace steps in the handling of gene therapy products.
Acute lymphoblastic leukemia (ALL)
A type of cancer that occurs when the bone marrow produces a large number of immature lymphoblasts.
Adaptive immune response
A specific immune response to the infecting pathogen that is triggered when the innate immune response mechanisms are insufficient, and a threshold antigen dose is reached. It requires days or weeks to develop and will leave an immunological memory for a faster response to exposure of the same pathogen in the future.
Adeno-associated virus (AAV)
A small (25 nm), non-enveloped virus that packages a linear single-stranded DNA genome. AAV has not been identified as an etiologic agent of human disease and is a naturally “defective” virus that requires a helper virus for productive replication of its genome. It has the ability to infect both dividing and non-dividing cells.
A member of a group of DNA viruses, originally discovered in adenoid tissue, most of which cause respiratory diseases. They can infect dividing and non-dividing cells.
An X-linked recessive genetic disorder caused by an abnormality in the ABCD1 gene on the X chromosome. This condition affects the white matter of the nervous system and the adrenal cortex.
A suspension of fine solid or liquid particles in gas.
Alpha‐1 antitrypsin deficiency
A genetic disorder that may cause lung disease and liver disease. It is inherited in an autosomal codominant manner and caused by mutations in the SERPINA1 gene.
A group of rare and diverse disorders caused by the deficiency of an enzyme or transporter involved in amino acid metabolism.
Amyotrophic lateral sclerosis (ALS)
Also known as Lou Gehrig’s disease. It is characterized by progressive degeneration and eventual death of motor neurons in the brain, brainstem, and spinal cord. Mutations in several genes (e.g. C9orf72, SOD1, TARDBP, and FUS) can cause familial ALS and contribute to the development of sporadic ALS. Most cases of ALS are sporadic, but a small percentage can be inherited.
A protein produced by the immune system in response to an antigen. Antibodies bind specifically to their target antigen to help the immune system destroy the foreign entity.
Antibody titer (test)
A laboratory test that measures the level of antibodies in a blood sample.
Any substance capable of inducing an immune response. Antigens include toxins, chemicals, bacteria, viruses, or other substances that come from outside the body.
Antigen-presenting cell (APC)
A heterogeneous group of immune cells that mediate the cellular immune response by processing and presenting antigens for recognition by certain lymphocytes such as T cells. Classical antigen-presenting cells include dendritic cells, macrophages, Langerhans cells, and B cells.
Antisense oligonucleotide (ASO)
Synthetic, short, single-stranded DNA or RNA molecules that interact with messenger RNA (mRNA) through base pairing to prevent translation of a targeted gene. Also known as “molecular patches”.
Aromatic L‐amino acid decarboxylase (AADC) deficiency
A genetic disorder that affects the way signals are passed between certain cells in the nervous system. It is inherited in an autosomal recessive manner and caused by mutations in the DDC gene.
Refers to the manner of handling, preparing, and storing of medications and injection equipment/supplies (e.g. syringes, needles, and intravenous tubing) to prevent microbial contamination.
A modification that makes the replication of a vector defective.
A sterilizer in which items are exposed to steam at a specific pressure and temperature for an allotted amount of time.
Autologous stem cell transplantation (autoSCT)
A procedure in which a patient’s healthy stem cells (blood-forming cells) are collected from the blood or bone marrow before treatment, stored, and then given back to the patient after treatment. An autologous stem cell transplantation replaces a patient’s stem cells that were destroyed by treatment with radiation or high doses of chemotherapy. It is most often used to treat blood cancers, such as leukemia and lymphoma.
Autosomal dominant (inheritance pattern)
It occurs when one mutated copy of the gene in each cell is sufficient for a person to be affected by an autosomal dominant disorder.
Autosomal recessive (inheritance pattern)
It occurs when mutations in both copies of the gene in each cell are needed to cause an autosomal recessive disease.
B lymphocytes (or B cells)
One of the two types of lymphocytes that makes antibodies. B cells are involved in humoral immunity; on encountering a foreign substance (antigen), the B lymphocyte differentiates into a plasma cell, which secretes immunoglobulin.
B-cell lymphoma (BCL)
A type of cancer that forms in B cells. Most B-cell lymphomas are non-Hodgkin lymphomas.
B-cell precursor acute lymphoblastic leukemia
An aggressive type of leukemia in which too many B-cell lymphoblasts (immature white blood cells) are found in the bone marrow and blood. It is the most common type of acute lymphoblastic leukemia (ALL). Also called B-cell acute lymphoblastic leukemia and B-cell acute lymphocytic leukemia.
A broad class of rare, fatal, inherited disorders of the nervous system, also known as neuronal ceroid lipofuscinoses, or NCLs, which interfere with a cell’s ability to recycle certain molecules. Each form is caused by a mutation in a different gene.
Becker muscular dystrophy
A genetic disorder that causes progressive weakness and wasting of the skeletal and cardiac (heart) muscles. It is an X-linked recessive disease caused by mutations in the gene encoding for the dystrophin protein.
Biallelic RPE65 mutation-associated retinal dystrophy
An inherited mutation in both alleles of the RPE65 gene resulting in degeneration of photoreceptors in the retina. The RPE65 gene is responsible for encoding retinal pigment epithelium-specific 65 kDa proteins.
Binding antibody (non-neutralizing antibody)
An antibody that binds specifically to virus particles, but do not neutralize infectivity.
The distribution (static and dynamic) of compounds within a biological system or within an organism.
A biological agent or condition that is a hazard to humans or the environment.
Biosafety cabinet (biological safety cabinet)
Specialized type of laboratory equipment designed to provide both a clean work environment and protection for employees who create aerosols when working with infectious agents or toxins. There are three classes of biosafety cabinets designated in the United States: Class I, Class II, and Class III. Most biosafety cabinets (e.g. Class II and Class III) use high-efficiency particulate air (HEPA) filters in both the exhaust and supply system to prevent exposure to biohazards.
Each of the four levels that can be assigned to laboratory facilities based on a composite of the design features, construction, containment facilities, equipment, practices, and operational procedures required for working with infective organisms.
An inherited disorder in which the body is unable to recycle the vitamin biotin. It is inherited in an autosomal recessive manner and caused by mutations in the BTD gene.
Blood–brain barrier (BBB)
A network of blood vessels and tissue that is made up of closely spaced cells and helps to keep harmful substances from reaching the brain.
Bone marrow transplantation
A procedure to replace damaged or destroyed bone marrow with healthy bone marrow stem cells.
C-reactive protein (CRP)
An acute phase reactant protein made by the liver that is released into the blood within a few hours after tissue injury, the start of an infection, or other inflammation. It is often the first evidence of inflammation or an infection in the body, with rising concentrations frequently preceding pain, fever, or other clinical indicators.
A rare genetic disorder that damages the ability of nerve cells (neurons) in the brain to send and receive messages. This disease is one of a group of genetic disorders called leukodystrophies. It is caused by mutations in the ASPA gene and inherited in an autosomal recessive manner.
The protein coat of a virus.
A condition affecting the heart or blood vessels. It is usually associated with a build-up of fatty deposits inside the arteries (atherosclerosis) and an increased risk of blood clots. It can also be associated with damage to arteries in organs such as the brain, heart, kidneys, and eyes.
A transmembrane glycoprotein expressed on the surface of hematopoietic progenitor cells and small blood vessel endothelial cells. While the specific function of CD34 remains to be elucidated, it is regarded as a marker of hematopoietic stem cells (HSCs) and hematopoietic progenitor cells.
CD4+ T cells
Also called helper T cells. They recognize peptides presented on major histocompatibility complex (MHC) Class II molecules, which are found on antigen-presenting cells. CD4+ T cells play a major role in instigating and shaping adaptive immune responses.
CD8+ T cells
Also called cytotoxic T lymphocytes, or CTLs. They are generated in the thymus and express the T-cell receptor. CD8+ T cells recognize peptides presented by major histocompatibility complex (MHC) Class I molecules and are important for immune defense against intracellular pathogens, including viruses and bacteria, and for tumor surveillance.
A technology that relies on replacing diseased or dysfunctional cells with healthy, functioning ones.
The genetic modification of cells outside the body. Also referred to as ex vivo gene therapy.
A type of adaptive immune response that occurs inside infected cells and is mediated by T lymphocytes. The pathogen's antigens are expressed on the cell surface or on an antigen-presenting cell. Helper T cells release cytokines that help activated T cells bind to the infected cells’ major histocompatibility complex (MHC)–antigen complex and differentiate the T cell into a cytotoxic T cell. The infected cell then undergoes lysis.
The use of small molecule ligands (chaperones) that selectively bind to and stabilize misfolded, mutant proteins. Chaperones can assist misfolded enzymes in becoming functional by helping them to fold properly and remain stable.
A type of cytokine that plays important roles in the body’s immune response, including attracting white blood cells to areas of inflammation to help the body fight infections, inflammatory conditions, and other diseases.
A treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.
Chimeric antigen receptor (CAR)
A recombinant receptor with both tumor antigen-binding and T-cell–activating functions.
Chimeric antigen receptor T-cell (immuno)therapy (CAR-T)
A gene therapy approach by which patient’s T cells are engineered to express chimeric antigen receptors or CARs.
A condition characterized by progressive vision loss that mainly affects males. It is inherited in an X-linked recessive pattern and caused by mutations in the CHM gene.
The material of chromosomes. It is a complex of DNA, histones, and non-histone proteins found within the nucleus of a cell.
Chronic granulomatous disease (CGD)
An inherited primary immunodeficiency disease that increases the body’s susceptibility to infections caused by certain bacteria and fungi. It can be caused by mutations in CYBB gene (X-linked recessive patterns) or in the CYBA, NCF1, NCF2, or NCF4 genes (inherited in an autosomal recessive pattern).
Clinical biosafety committee
A cross-departmental institutional committee that evaluates approved gene therapy products and develops and standardizes protocols for their safe handling.
A genetic disorder that primarily affects the nervous system. CLN2 disease is one of a group of disorders known as neuronal ceroid lipofuscinoses (NCLs), which may also be collectively referred to as Batten disease. It is inherited in an autosomal recessive manner and caused by mutations in the TPP1 gene.
Clustered regularly interspaced short palindromic repeat (CRISPR)
A family of DNA sequences found in the genomes of prokaryotic organisms such as bacteria and archaea that consists of short repeated sequences separated by spacers derived from nucleic acid of viruses and plasmids. The spacers are used as recognition elements to ﬁnd matching virus genomes and destroy them. CRISPR-associated protein 9 (Cas9) enzymes, together with CRISPR sequences, form the basis of a technology known as CRISPR–Cas9 that can be used to edit genes within organisms.
Disorders of intracellular cobalamin metabolism that can result from deficient synthesis of the coenzymes derived from vitamin B12.
A non-protein chemical that assists with a biological chemical reaction.
A heat-labile component of normal plasma that causes the opsonization and killing of bacteria. The complement system refers to a series of >20 proteins, circulating in the blood and tissue fluids. Most of the proteins are normally inactive; however, in response to the recognition of molecular components of microorganisms, they become sequentially activated in an enzyme cascade.
A DNA copy of a messenger RNA (mRNA) molecule produced by reverse transcriptase, a DNA polymerase that can use either DNA or RNA as a template.
A disease caused by a combination of genetic, environmental, and lifestyle factors.
The process of combining, mixing, or altering ingredients to produce a medication tailored to the needs of an individual patient.
Congenital enzyme deficiencies
Enzyme deficiencies, usually inherited in a recessive fashion, caused by loss-of-function mutations. They may be autosomal recessive or X-linked recessive.
A genetic severe disorder characterized by hyperbilirubinemia. It is inherited in an autosomal recessive manner and caused by mutations in the UGT1A1 gene.
CRISPR-associated protein 9 (Cas9)
An enzyme that uses clustered regularly interspaced short palindromic repeat (CRISPR) sequences as a guide to recognize and cleave specific strands of DNA that are complementary to the CRISPR sequence. Cas9 enzymes, together with CRISPR sequences, form the basis of a technology known as CRISPR–Cas9 that can be used to edit genes within organisms.
Inadvertent transfer of bacteria or other contaminants from one surface, substance, etc., to another especially because of unsanitary handling procedures.
Cystic fibrosis (CF)
A genetic disease characterized by the build-up of thick, sticky mucus that can damage many of the body's organs. It is inherited in an autosomal recessive manner and is caused by mutations in the CFTR gene. The CFTR gene encodes cystic fibrosis transmembrane conductance regulator proteins.
Small secreted proteins released by cells that have a specific effect on the interactions and communications between cells. They can be made by immune and non-immune cells. Examples of cytokines include interleukins, interferons, and colony-stimulating factors.
Cytokine release syndrome (CRS)
A condition that may occur after treatment with some types of immunotherapy, such as monoclonal antibodies and chimeric antigen receptor T cells (CAR-T cells). Cytokine release syndrome is caused by a large, rapid release of cytokines into the blood from immune cells affected by the immunotherapy. Signs and symptoms of cytokine release syndrome include fever, nausea, headache, rash, rapid heartbeat, low blood pressure, and trouble breathing. Most patients have a mild reaction, but sometimes, the reaction may be severe or life-threatening.
A condition in which the number of blood cells is lower than normal.
A substance that kills cells, including cancer cells.
A type of genetic alteration involving the removal of a piece of DNA, resulting in a reduction in the number of DNA base pairs. It can occur within one gene, resulting in the loss of base pairs in that gene, or could result in deletion of a section of a chromosome, resulting in the removal of one or several neighboring genes.
A bone marrow-derived leukocyte that is the most potent type of antigen-presenting cell. Named for their probing, “tree-like” or dendritic shapes, dendritic cells are responsible for the initiation of adaptive immune responses and function as the “sentinels” of the immune system.
Diffuse large B-cell lymphoma (DLBCL)
The most common type of non-Hodgkin lymphoma, marked by rapidly growing tumors in the lymph nodes, spleen, liver, bone marrow, or other organs.
Cells that contain two copies of each chromosome.
Direct injection of viral vector into the patient. Also referred to as in vivo gene therapy.
A process that eliminates many or all pathogenic microorganisms, except bacterial spores, on inanimate objects.
A mutation whose gene product adversely affects the normal, wild-type gene product within the same cell. This usually occurs if the product can still interact with the same elements as the wild-type product, but blocks some aspect of its function.
Duchenne muscular dystrophy (DMD)
A rare muscular dystrophy, but one of the most frequent genetic conditions in boys, caused by mutations of the DMD gene on the X chromosome that regulates the production of dystrophin, a protein found in the membrane of skeletal and cardiac muscle cells.
A type of genetic alteration that consists of a piece of DNA being copied once or many more times. This duplication could occur within the same gene or result in duplication of a section of a chromosome (chromosomal duplication), resulting in multiple copies of genes within that chromosomal region.
A group of dystrophies resulting from mutations in the dystrophin (DMD) gene, located on the short arm of the X chromosome in the Xp21 region. They cover a spectrum of X-linked muscle diseases ranging from mild to severe that includes Duchenne muscular dystrophy, Becker muscular dystrophy, and DMD-associated dilated cardiomyopathy (DCM).
Electroporation (or electropermeabilization)
A molecular biology technique in which a high-voltage electrical pulse is applied to cells in order to increase the permeability of the cell membrane, allowing chemicals, drugs, or DNA to be introduced into the cell.
A biological catalyst, almost always a protein, that speeds up the rate of a specific chemical reaction in the cell.
A heritable alteration that changes DNA accessibility and chromatin structure, thereby regulating patterns of gene expression.
In bacterial genetics, an extrachromosomal DNA molecule that can exist and replicate autonomously in the cytoplasm or as a part of a chromosome. In gene therapy, this can also refer to genetic material introduced into a cell by a vector that does not integrate into the host DNA but instead persists in an extrachromosomal form.
Also called antigenic determinant. It is a portion of a foreign protein, or antigen, that is capable of stimulating an immune response. An epitope is the part of the antigen that binds to a specific antigen receptor on the surface of a B cell.
Ex vivo gene therapy
The genetic modification of cells outside the body. Also referred to as cell-based therapy.
Part of a gene sequence that is expressed in the mature messenger RNA, encoding the amino acids of a protein.
The process of skipping exons with disease-causing mutations and/or nearby exons to restore the reading frame, which results in an internally truncated, partially functional protein.
A component of vector DNA comprising the gene (or genes) of interest and regulatory sequences controlling transgene expression.
A genetic disorder that results from the build-up of globotriaosylceramide in the body's cells. It is inherited in an X-linked pattern and caused by mutations in the GLA gene. The GLA gene encodes the enzyme galactosidase alpha.
Facioscapulohumeral muscular dystrophy (FSHD)
An inherited condition characterized by muscle weakness and wasting (atrophy). There are two types of FSHD (FSHD1 and FSHD2), both caused by overexpression of the DUX4 gene (due to hypomethylation in the D4Z4 region of chromosome 4). FSHD1 is caused by a shorter D4Z4 region and is inherited in an autosomal dominant manner. FSHD2 is inherited in a digenic pattern (two independent genetic changes are necessary) and occurs as a result of mutations in the SMCHD1 gene and the presence of a “permissive” chromosome 4 that allows for production of DUX4 protein.
Familial adenomatous polyposis (FAP)
An inherited disorder characterized by cancer of the colon and rectum. It can be inherited in an autosomal dominant or recessive manner when caused by mutations in the APC or MUTYH gene, respectively.
Familial hypercholesterolemia (FH)
A genetic disorder caused by a defect in chromosome 19, leading to high cholesterol. The condition begins at birth and can cause heart attacks at an early age.
Familial lipoprotein lipase deficiency
A genetic condition that disrupts the normal breakdown of fats in the body, resulting in an increase in certain kinds of fats. It is inherited in an autosomal recessive manner and is caused by mutations in the LPL gene, encoding lipoprotein lipase.
A genetic disorder that mainly affects many parts of the body. It may lead to bone marrow failure, physical abnormalities, organ defects, and an increased risk of certain cancers. It is mainly inherited in an autosomal recessive manner, but it can also be X-linked. It can be caused by mutations in at least 15 genes.
A ubiquitous protein found in all cells and the primary site of iron storage in the cell. Ferritin concentrates cellular iron and protects cells from its toxic effects.
A mutation that confers new or enhanced activity on a protein.
A group of autosomal recessive inherited disorders that impair the body's ability to process and produce energy from galactose due to the deficiency of any of three enzymes, caused by mutations in different genes.
A genetic condition that affects many areas in the body. There are three forms of galactosialidosis that are distinguished by the age at which symptoms develop and the pattern of features. Galactosialidosis is an autosomal recessive lysosomal storage disorder caused by mutations in the CTSA gene.
Also known as onco-retroviruses. These consist of a large number of leukemia and sarcoma viruses of mice, cats, primates, and other mammals.
An autosomal recessive inherited disorder caused by mutations in the GBA gene, resulting in the build-up of a fatty substance called glucocerebroside and related substances, and subsequent damage to tissues and organs.
The use of engineered or bacterial nucleases for targeted modifications of the genome to prevent or treat a disease.
Also called biolistic gene transfer. This technique involves bombarding target cells with DNA-coated gold particles driven by pressurized inert gas, such as helium, or by high-voltage electronic discharge.
Deactivating or “silencing” the expression of a mutated gene that is not functioning properly.
The introduction of a complementary DNA construct or modified gene that expresses a functional protein that is absent, reduced, or non-functional due to a mutated gene in an effort to correct the disease.
A process that involves the interruption or suppression of the expression of a gene at the transcriptional or translational level.
The introduction of genetic material into an individual, or the modification of the individual’s genetic material, in order to achieve a therapeutic objective.
The insertion of exogenous genetic information in the form of DNA into cells.
Genetic modulation of immune cells
The introduction of a complementary DNA construct or modified gene that promotes a stronger immune response to attack diseased cells.
Germline gene therapy
Direct manipulation of genetic material in oocytes, sperm, zygotes, or embryos. It affects all tissues of the developing fetus, including germ cells, and therefore the genetic alteration would be passed on to future generations.
A complication of bone marrow transplants in which T cells in the donor bone marrow graft attack the host's tissue. It often occurs when the blood marrow donor is unrelated to the patient or not a perfect match. There are two forms: an early acute form and a chronic form.
A family of serine proteases released by cytoplasmic granules within cytotoxic T cells and natural killer (NK) cells. They can play an important role in the apoptosis of the target cell.
A genetic condition characterized by progressive degeneration of the choroid and pigment epithelium of the retina, leading to progressive vision loss. Gyrate atrophy is inherited in an autosomal recessive manner and it is caused by mutations in the OAT gene.
Hairpin (loop) structure
A hairpin loop (usually in messenger RNA [mRNA]) forms when an mRNA strand folds and forms base pairs with another section of the same strand.
A situation in which the total level of a gene product (a particular protein) produced by the cell is about half of the normal level and is not sufficient to permit the cell to function normally. It can also be defined as a condition that arises when the normal phenotype requires the protein product of both alleles, and reduction of 50% of gene function results in an abnormal phenotype.
A virus that enables genetically modified viruses to replicate or to form a protein coat by complementing the missing gene function of the defective virus.
Hematopoietic stem cells (HSCs)
Cells residing in the bone marrow that have the capacity to regenerate all the different types of blood cells.
A bleeding disorder that slows the blood-clotting process. It is inherited in an X-linked recessive pattern and can be caused by mutations in the F8 gene (hemophilia A), or F9 gene (hemophilia B).
An infection of the liver caused by the hepatitis B virus that can spread through blood and body fluids.
Herpes simplex virus (HSV)
A virus that causes herpes, a lifelong infection. There are two types of herpes simplex virus: HSV type 1 (HSV-1) and HSV type 2 (HSV-2).
Human immunodeficiency virus (HIV)
A virus that damages the cells in the immune system and weakens their ability to fight everyday infections and disease. Acquired immune deficiency syndrome (AIDS) is the name used to describe a number of potentially life-threatening infections and illnesses that happen when the immune system has been severely damaged by HIV.
A type of adaptive immune response that is mediated by antibody molecules that are secreted by plasma cells. In this response, antibodies produced by B cells cause the destruction of extracellular microorganisms and prevent the spread of intracellular infections.
Huntington’s disease (HD)
A progressive brain disorder that causes uncontrolled movements, emotional problems, and loss of thinking ability (cognition). It is inherited in an autosomal dominant pattern and caused by mutations in the huntingtin gene (HTT).
Specific sites in the mammalian body, such as the eyes, brain, testis, and placenta, that are able to tolerate the introduction of antigens without eliciting an inflammatory immune response.
The ability of a molecule or substance to provoke an immune response, or the strength or magnitude of an immune response.
An agent that can suppress or prevent the immune response. Immunosuppressants can be used to prevent rejection of a transplanted organ and to treat autoimmune diseases.
A type of therapy that uses substances to stimulate or suppress the immune system to help the body fight cancer, infection, and other diseases.
In vivo gene therapy
Direct injection of viral vector into the patient. Also referred to as direct delivery.
A disease caused by pathogenic microorganism(s), such as bacteria, viruses, parasites, or fungi; the disease can be spread, directly or indirectly, from one person to another.
A multiprotein intracellular complex that detects pathogenic microorganisms and sterile stressors, and that activates the highly pro-inflammatory cytokines interleukin (IL)-1b and IL-18. Inflammasomes also induce a form of cell death termed pyroptosis.
A vast array of disorders and conditions that are characterized by inflammation. Examples include allergy, asthma, autoimmune diseases, celiac disease, glomerulonephritis, hepatitis, inflammatory bowel disease, preperfusion injury, and transplant rejection.
Innate immune response
A rapid, non-specific immune response that develops hours after an infection. It is crucial for the initiation of an adaptive immune response.
The process by which an exogenous DNA sequence integrates within the genome of a host organism. It can result in the disruption of the host gene(s) and lead to perturbation of the cellular phenotype.
Integrating viral vector
Viral DNA from integrating viral vectors translocates into the nucleus and integrates into the host genome, leading to stable, long-lasting transgene expression.
A natural substance that helps the body’s immune system fight infection and other diseases, such as cancer. An interferon is a type of cytokine and type of immunomodulating agent. There are three main types of interferon: alpha, beta, and gamma.
One of a group of related proteins made by leukocytes (white blood cells) and other cells in the body that regulate immune responses. An interleukin is a type of cytokine.
Referring to situated in, occurring in, or administered by entering a muscle.
Referring to situated, performed, or occurring within or entering by way of a vein.
Non-coding regions of a gene, not expressed in the mature messenger RNA, that are in between exons in the gene.
A type of genetic alteration that occurs when two breaks occur in one chromosome and the region between the breaks flips 180 degrees before rejoining with the two end fragments, thereby resulting in the sequence being reversed. Inversions can occur within a single gene or can occur across several genes in one chromosome.
Inverted terminal repeat
A sequence of nucleotides that is repeated nearly without change except in the opposite direction, usually at some point distant from the original sequence; often associated with gene insertion.
Junctional epidermolysis bullosa (JEB)
A group of genetic conditions that cause the skin to be very fragile and to blister easily. It is inherited in an autosomal recessive pattern and most commonly results from mutations in the LAMA3, LAMB3, LAMC2, and COL17A1 genes.
Also called globoid cell leukodystrophy. It is a severe neurological condition that is part of a group of disorders known as leukodystrophies, which result from the loss of myelin in the nervous system. It is inherited in an autosomal recessive pattern and caused by mutations in the GALC gene.
Laminar flow biological safety cabinet
A laboratory enclosure designed to carefully direct high-efficiency particulate (HEPA) filtered air.
Referring to the property of a virus to persist indefinitely in their host after a primary or secondary infection.
Leber congenital amaurosis (LCA)
An eye disorder that primarily affects the retina. It can result from mutations in at least 14 genes (including RPE65). It usually has an autosomal recessive pattern of inheritance.
A subclass of retroviruses characterized by long incubation periods and persistent infection. Lentiviruses have the ability to integrate into the genome of both dividing and non-dividing cells.
Removal of the blood to collect specific blood cells. The remaining blood is returned to the body.
A type of cancer that occurs when the bone marrow produces too many abnormal white blood cells (lymphocytes) affecting the blood and the bone marrow. The types of leukemia include acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML).
Leukocyte adhesion deficiency (LAD)
A defect of cellular adhesion molecules resulting in clinical syndromes. It is a combined (B cell) and cellular (T cell) immunodeficiency disorder. There are three different types of LAD (types I, II, and III). It is inherited in an autosomal recessive manner and it can be caused by mutations in at least seven genes.
Limb-girdle muscular dystrophy (LGMD)
A group of diseases that cause weakness and wasting of the muscles in the arms and legs. It can have different inheritance patterns and be caused by mutations in many different genes.
Lipoplex (cationic liposomes)
Non-viral (synthetic) lipid carriers of DNA. Due to their positive surface charge, they can form complexes with negatively charged DNA.
An artificial vesicle composed of one or more concentric phospholipid bilayers that is often used to deliver microscopic substances (such as drugs or DNA) to target tissues.
Long-chain fatty acid oxidation disorder
Also called long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency. It is a rare condition that prevents the body from converting certain fats to energy, particularly during fasting. It is inherited in an autosomal recessive manner and caused by mutations in the HADHA gene.
A mutation that results in reduced or abolished protein function.
A type of white blood cell (leukocyte) and one of the body's main types of immune cells. Lymphocytes are made in the bone marrow and are found in the blood and in lymph tissue. There are two categories of lymphocytes known as B lymphocytes (or B cells) and T lymphocytes (or T cells).
A type of cancer that begins in the immune system and affects the lymph nodes and lymphocytes. There are two types of lymphomas: Hodgkin lymphoma and non-Hodgkin lymphoma.
Lysosomal acid lipase deficiency
An inherited metabolic lipid storage disorder caused by mutations in the LIPA gene encoding for lysosomal acid lipase (LAL) protein, which is needed for the breakdown of lipids and cholesterol in the cells. Two conditions have been described: Wolman disease and cholesteryl ester storage disease. Lysosomal acid lipase deficiency is inherited in an autosomal recessive manner.
A specialized cell involved in the detection, phagocytosis, and destruction of bacteria and other harmful organisms. Macrophages can also present antigens to T cells and initiate inflammation by releasing cytokines that activate other cells. Macrophages originate from blood monocytes that leave the circulation to differentiate in different tissues.
A process that involves attaching DNA to supramagnetic iron oxide nanoparticles coated with a cationic polymer, in the presence of a magnetic field, to mediate the delivery of the attached DNA into the target organ.
Major histocompatibility complex (genes) (MHC)
A group of genes that code for proteins found on the surfaces of cells that help the immune system recognize foreign substances. In humans, the major histocompatibility complex is also called the human leukocyte antigen (HLA) system.
Maple syrup urine disease
A genetic disorder in which the body is unable to process amino acids properly, giving a distinctive sweet odor of affected infants' urine, and characterized by poor feeding, vomiting, lack of energy (lethargy), abnormal movements, and delayed development. It is inherited in an autosomal recessive pattern, and caused by mutations in the BCKDHA, BCKDHB, or DBT gene.
An autosomal dominant disorder that affects the connective tissue in many parts of the body. It is caused by mutations in the FBN1 gene.
A genetic disorder characterized by the accumulation of fats called sulfatides in cells affecting mainly the white matter of the brain and causing progressive deterioration of intellectual functions and motor skills, such as the ability to walk. It is inherited in an autosomal recessive manner and caused by mutations in the ARSA or PSAP gene.
A genetic disorder in which the body is unable to process certain proteins and lipids properly. It is inherited in an autosomal recessive pattern and is caused by mutations in the MMUT, MMAA, MMAB, MMADHC, or MCEE gene.
A process where harvested cells are mechanically disrupted with a very high efficiency. It can be used to collect viruses for large-scale manufacturing of adeno-associated virus (AAV) vectors.
A small non-coding RNA molecule (~22 nucleotides) that functions in RNA silencing and post-transcriptional regulation of gene expression.
An episomal DNA vector that is produced as a circular expression cassette lacking any bacterial plasmid DNA backbone.
A genetic disease that results from modifications in a single gene occurring in all cells of the body.
A group of inherited conditions in which the body is unable to properly break down mucopolysaccharides. As a result, these sugars build up in cells, blood, and connective tissue, which can lead to a variety of health problems.
Muscular dystrophy (MD)
A group of genetic diseases that cause the weakening of muscles over time. Muscular dystrophies are caused by mutations in genes responsible for the structure and functioning of a person’s muscles, and often inherited.
A disorder that occurs when blood flow to the heart is reduced, preventing the heart muscle from receiving enough oxygen. The reduced blood flow is usually the result of a partial or complete blockage of the heart's arteries (coronary arteries). It is also called cardiac ischemia.
Natural killer (NK) cell
A type of lymphocyte that plays a major role in the host rejection of both tumor cells and virally infected cells. Natural killer cells serve to contain viral infections while the adaptive immune response is generating antigen-specific cytotoxic T cells that can clear the infection.
A genetic disorder that affects the skin, hair, and immune system. It is inherited in an autosomal recessive pattern and is caused by mutations in the SPINK5 gene.
A disease of the central and peripheral nervous system (i.e. brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscles).
A binding antibody that is capable of keeping an infectious agent, usually a virus, from infecting a cell by neutralizing or inhibiting its biological effect, for example by blocking the receptors on the cell or the virus.
One of the first white blood cells that travels to the site of an infection. Neutrophils help fight infection by ingesting microorganisms and releasing enzymes that kill the microorganisms. A neutrophil is a type of granulocyte and a type of phagocyte.
Niemann–Pick disease type C
A rare, progressive genetic disorder characterized by an inability of the body to transport cholesterol and other fatty substances (lipids) inside of cells. It is inherited in an autosomal recessive manner and caused by mutations in the NPC1 or NPC2 gene.
A type of cancer that develops in the lymphatic system, a network of vessels and glands spread throughout the body.
Non-integrating viral vector
The genetic material of non-integrating vectors remains in the cytoplasm in episomal form and does not integrate into the host genome.
Non-viral delivery systems
Comprise all the physical and chemical systems for delivery of gene therapy except viral systems, and generally include either chemical methods (such as cationic liposomes and polymers) or physical methods (such as gene gun, electroporation, particle bombardment, ultrasound utilization, and magnetofection).
The substitution of a single base pair that leads to the appearance of a stop codon where previously there was a codon specifying an amino acid. The presence of this premature stop codon results in the production of a shortened, and likely non-functional, protein.
Off-target genome editing
Non-specific genetic modifications as a result of a designed genome editing process, including point mutations, deletions, insertions, inversions, and translocations of unexpected genes.
The process through which healthy cells become transformed into cancer cells. Oncogenesis is characterized by a series of genetic and cellular changes, including oncogene activation, that lead cells to divide in an uncontrolled manner.
A form of immunotherapy that uses viruses to infect and destroy cancer cells.
A process where microorganisms and inanimate colloids (e.g. liposomes, particulates) are coated with host-produced proteins and lipids (immunoglobulins, complement factors), thus facilitating the binding of the opsonized bacteria or particle to specific receptor molecules present on phagocytes (i.e. neutrophils, macrophage, dendritic cells).
A group of metabolic disorders resulting from enzymatic deficiencies in the catabolic pathway of branched-chain amino acids and lysine, leading to the accumulation of organic acids in the body fluids and tissues. Most organic acidemias have autosomal recessive inheritance patterns.
Ornithine transcarbamylase deficiency
A genetic disorder characterized by complete or partial lack of the enzyme ornithine transcarboxylase, resulting in accumulation of ammonia in the blood. It is an X-linked disorder caused by mutations in the OTC gene.
Any of a family (Parvoviridae) of single-stranded DNA viruses that include the causative agents of fifth disease in humans, panleukopenia in cats, and parvovirus in dogs.
Pathogen-associated molecular patterns (PAMPs)
Molecules that activate innate immune responses, protecting the host from infection, by the recognition of some conserved non-self molecules on pathogens.
A state in which the virus is not cleared but remains in specific cells of infected individuals.
Personal protective equipment (PPE)
Equipment that will protect the user against health or safety risks at work, such as safety helmets, gloves, eye protection, high-visibility clothing, safety footwear, safety harnesses, and respiratory protective equipment (RPE).
A type of leukocyte capable of phagocytosis (a specific form of endocytosis by which cells internalize solid matter, including microbial pathogens). Macrophages, neutrophils, and immature dendritic cells are types of phagocytes.
The process by which certain living cells called phagocytes ingest or engulf other cells or particles. The phagocyte may be a free-living one-celled organism, such as an amoeba, or one of the body cells, such as a white blood cell.
The observable physical properties of an organism, such as appearance, development, and behavior. Phenotype is determined by genotype and environmental influences.
An inherited disorder that increases the levels of the amino acid phenylalanine in the blood, which can lead to intellectual disability and other serious health problems. It is inherited in an autosomal recessive manner and caused by mutations in the PAH gene.
A small extrachromosomal ring of DNA, especially of bacteria, that can replicate independently and can be taken from one organism and inserted into another.
The simultaneous malfunction of many peripheral nerves throughout the body.
A complex of a polymer and DNA designed to carry genetic material and protect DNA from degradation during delivery into target tissue.
A genetic disorder caused by the build-up of glycogen in the body's cells. The accumulation of glycogen in certain organs and tissues, especially muscles, impairs their ability to function normally. Pompe disease is inherited in an autosomal recessive manner and caused by mutations in the GAA gene.
Premature stop codon
A mutation that results in the coding of a stop codon prematurely in the protein-coding gene sequence.
The primary means of physical containment include laboratory practices and the use of containment equipment within the laboratory.
Primary mediastinal large B-cell lymphoma (PMBCL)
An aggressive type of B-cell non-Hodgkin lymphoma that develops from B cells in the mediastinum.
A DNA sequence typically located directly upstream or at the 5' end of the transcription initiation site that defines where transcription of a gene by RNA polymerase begins.
Also known as propionic acidemia or propionyl-CoA carboxylase deficiency. A genetic disorder in which the body is unable to process certain parts of proteins and lipids properly, leading to an abnormal build-up of organic acids in the blood, urine, and tissues. Propionic aciduria is inherited in an autosomal recessive pattern and caused by mutations in the PCCA or PCCB genes.
A normal gene that, when altered by mutation, becomes an oncogene that can contribute to cancer. Mutations in proto-oncogenes are typically dominant in nature, and the mutated version of a proto-oncogene is called an oncogene.
A process of producing viruses or viral vectors in combination with foreign viral envelope proteins.
One of the three possible ways to read a nucleotide sequence in DNA, depending on whether reading starts with the first, second, or third base in a triplet.
Recombinant DNA (technology)
A technology that involves either the combining of DNA from different genomes or the insertion of foreign DNA into a genome.
Regulatory T cell (Treg)
A T cell that has a role in regulating or suppressing other cells in the immune system. Regulatory T cells control the immune response to self and foreign particles (antigens) and help prevent autoimmune disease.
In viral vectors, it enables each cell infected to become a vector-producing cell that gives rise to more vectors and thus more efficient transduction.
In viral vectors, characterized by being defective in one or more functions that are essential for viral genome replication or synthesis and assembly of viral particles.
A complex set of hereditary diseases of the retina that result in the degeneration of photoreceptors, rods, and/or cones.
A group of genetic related eye disorders that cause progressive vision loss. More than 60 genes are known to cause retinitis pigmentosa. It can be inherited in an autosomal dominant or recessive manner, or it can be X-linked.
A type of RNA virus that reverse transcribes its RNA into DNA and inserts this DNA copy into the genome of the host cell. Retroviruses only infect dividing cells.
A neurodevelopmental disorder that affects girls almost exclusively. Nearly all cases are caused by a mutation in the methyl CpG-binding protein 2 or MECP2 gene.
Classifications that describe the relative hazard posed by infectious agents or toxins in the laboratory.
RNA interference (RNAi)
Sequence-specific “post-transcriptional inhibition” of gene expression mediated by small double-stranded RNAs.
An enzyme that catalyzes DNA template-directed extension of the 3' end of an RNA strand, one nucleotide at a time. RNA polymerase can initiate the synthesis of a chain de novo. In eukaryotes, there are three distinct types of RNA polymerases.
RNA-induced silencing complex (RISC)
A multiprotein complex, specifically a ribonucleoprotein, which incorporates one strand of a single-stranded RNA fragment, such as microRNA (miRNA), or double-stranded small interfering RNA (siRNA) and uses the RNA as a template for recognizing complementary messenger RNA. When it finds a complementary strand, the RNA-induced silencing complex activates RNase and cleaves the RNA.
A phenotypically silent mutation caused by a point mutation that gives rise to a different codon, which is transcribed as a “synonymous” codon. The same amino acid is incorporated into the growing polypeptide as would have been incorporated by the original, non-mutated codon and the protein remains unchanged.
The promotion of hygiene and prevention of disease by maintenance of sanitary conditions (as by removal of sewage and trash).
The development of detectable antibodies in the blood that are directed against an infectious agent.
The proportion of a population that is seropositive (i.e. has been exposed to a particular pathogen or immunogen).
The state of either having (seropositive) or not having (seronegative) detectable antibodies against a specific antigen, as measured by a blood test (serologic test).
A group of intimately related microorganisms, e.g. viruses, within a single species that share distinctive surface structures.
Severe combined immunodeficiency (SCID)
A group of genetic disorders caused by mutations in genes involved in the development and function of infection-fighting immune cells. More than a dozen genes have been implicated in SCID. SCID is often inherited in an autosomal recessive pattern, but X-linked SCID can also occur. The best-known form of autosomal recessive SCID is caused by adenosine deaminase (ADA) deficiency, in which infants lack the ADA enzyme necessary for T-cell survival.
Short hairpin RNA or small hairpin RNA (shRNA)
A short sequence of RNA that makes a tight hairpin turn and can be used to silence gene expression.
Sickle cell anemia
A disorder in which atypical hemoglobin S molecules distort red blood cells into a sickle, or crescent, shape. It is inherited in an autosomal recessive manner and caused by mutations in the HBB gene.
Single nucleotide change
A type of genetic alteration that involves a change in a DNA base pair in the gene, causing a change in the amino acid encoded by the surrounding DNA sequence. A single nucleotide change can result in altered function of the resulting protein.
Small interfering RNA (siRNA)
Short, double-stranded RNA molecules usually 21–23 nucleotides in length, with a phosphate group at the 5’ end and a hydroxyl group at the 3’ end of each strand, and with a two-nucleotide overhang at the 3’ end of both strands. Small interfering RNAs target complementary messenger RNA for degradation.
Somatic gene therapy
The alteration of genetic material in diploid cells. It targets cells of individual organs or tissues and the effects are only maintained for the lifespan of the individual and not passed on to their offspring.
Spinal muscular atrophy
A group of genetic disorders that affects the lower motor neurons of the spinal cord and leads to progressive muscle weakness and paralysis. The most common form of spinal muscular atrophy is inherited in an autosomal recessive manner and is caused by mutations in both copies of the survival motor neuron 1 gene (SMN1) located on the long arm (q) of chromosome 5.
Squamous cell carcinoma (SCC)
A type of non-melanoma skin cancer that begins in the squamous cells.
Staff exposure log
A centrally held record of staff exposure to a gene therapy product within an institution.
Standard microbiological practice
Provides protection for laboratory workers and other employees in the building at Biosafety Level 1.
Stargardt disease (Stargardt macular dystrophy)
A genetic eye disorder that causes progressive vision loss. It can have different inheritance patterns and can be caused by mutations in different genes (ABCA4, ELOVL4).
A cell that possesses self-renewal capacity as well as the ability to differentiate into one or more mature cell types.
A process that destroys or eliminates all forms of microbial life and is carried out in healthcare facilities by physical or chemical methods.
A molecule acted upon by an enzyme.
Involves a treatment that affects the body as a whole or that acts specifically on systems that involve the entire body.
T lymphocytes (or T cells)
One of the two types of lymphocytes that help to destroy infected or cancerous cells. T cells are involved in adaptive immunity and determine the specificity of the immune response to antigens in the body. T cells originate in the bone marrow and mature in the thymus, where they multiply and differentiate into helper, regulatory, or cytotoxic T cells or become memory T cells.
A genetic disorder that progressively destroys neurons in the brain and spinal cord. The most common form of Tay–Sachs disease becomes apparent in infancy. It is inherited in an autosomal recessive pattern and is caused by mutations in the HEXA gene.
A group of inherited conditions that affect the production of hemoglobin. There are two main types of thalassemia: alpha and beta thalassemia.
Toll-like receptor (TLR)
A pattern recognition receptor that plays a crucial role in the initiation of innate immune response by detecting potential harmful pathogens.
The transference of information in DNA to a messenger RNA (mRNA) molecule.
Transcription termination signal
A section of nucleic acid sequence that marks the end of a gene or operon in genomic DNA during transcription.
Transcriptional start site
The location where transcription starts at the 5’ end of a gene sequence.
The process by which DNA is introduced into cells (by viral vectors).
A procedure that introduces foreign nucleic acids (DNA or RNA) into cells to produce genetically modified cells.
Transforming growth factor (TGF)
One of several proteins secreted by transformed cells that can stimulate the growth of normal cells. TGF alpha (TGF-α) binds the epidermal growth factor receptor (EGFR) and stimulates the growth of endothelial cells. TGF-beta (TGF-β) is found in hematopoietic (blood-forming) tissue and initiates a signaling pathway that suppresses the early development of cancer cells.
A gene or a segment of DNA that is introduced into the genome of another organism by artificial techniques.
The process of translating the sequence of a messenger RNA (mRNA) molecule to a sequence of amino acids during protein synthesis.
The continuation of translation beyond a stop codon by the use of a special transfer RNA (tRNA) that recognizes the UAG and UGA codons as modified amino acids, rather than as termination codons.
Discrete segments of DNA that can excise and reintegrate to another site in the genome.
A genetic, slowly progressive condition characterized by the build-up of abnormal deposits of a protein called amyloid (amyloidosis) in the body's organs and tissues. It is inherited in an autosomal dominant manner and caused by mutations in the TTR gene.
Determines which cells or tissues can become infected by any given pathogen (e.g. a virus).
Tumor necrosis factor (TNF)
A type of cytokine made by white blood cells in response to an antigen or infection. It may boost a person’s immune response, and also may cause necrosis (cell death) of some types of tumor cells.
A genetic disorder characterized by disruptions in the multistep process that breaks down tyrosine. It is inherited in an autosomal recessive pattern and caused by mutations in the FAH, TAT, or HPD gene.
U.S. Pharmacopeia General Chapter 800
Practice and quality standards for handling hazardous drugs to promote patient safety, worker safety, and environmental protection.
Ultrasound + microbubble
A non-invasive, site-specific technique, also known as sonoporation, which utilizes ultrasound waves to temporarily permeabilize the cell membrane to allow cellular update of DNA. Genetic material of interest is incorporated within microbubbles and administered into systemic circulation, followed by external application of ultrasound.
Untranslated region (UTR)
A non-protein coding section of the messenger RNA that can be recognized by specific RNA-binding proteins. Untranslated regions are important for the post-transcriptional regulation of gene expression. They can be located at the 5’ end of the coding region (5' UTR) or at the 3’ end of the coding region (3’ UTR).
Urea cycle disorder (UCD)
A disorder that results from genetic mutations causing defects in the metabolism of the extra nitrogen produced by the breakdown of protein and other nitrogen-containing molecules.
An alteration in the most common DNA nucleotide sequence. The term “variant” can be used to describe an alteration that may be benign, pathogenic, or of unknown significance. The term “variant” may be used in place of the term “mutation”.
A genetically engineered carrier that delivers genetic material into target cells or tissues.
The dissemination of the vector through secretions and/or excreta of the patient.
The lipid and protein bilayer that surrounds the capsid in some viruses.
Viral genome integration
The insertion of viral DNA into the host cell.
A naturally occurring virus that has been modified to deliver genetic material into cells.
Having the capacity to or tending to destroy or inactivate viruses.
A chain of biochemical reactions that regenerate visual pigment following exposure to light.
von Gierke disease (glycogen storage disease type Ia)
An inherited disorder caused by the build-up of glycogen in the body’s cells. It is inherited in an autosomal recessive pattern and is caused by mutations in the G6PC gene.
White blood cell (leukocyte or white corpuscle)
A cellular component of the blood that lacks hemoglobin, has a nucleus, is capable of motility, and defends the body against infection and disease by ingesting foreign materials and cellular debris, by destroying infectious agents and cancer cells, or by producing antibodies. White blood cells are grouped into three major classes—lymphocytes, granulocytes (neutrophils, eosinophils, and basophils), and monocytes—each of which carries out somewhat different functions.
A genetic disorder affecting the nervous system and the adrenal glands that is characterized by the progressive loss of myelin in the nervous system (reducing the ability of the nerves to relay information to the brain) and a shortage of certain hormones caused by damage to the outer layer of the adrenal glands (which may cause weakness, weight loss, skin changes, vomiting, and coma). It is inherited in an X-linked manner and caused by mutations in the ABCD1 gene.
X-linked dominant disorder
A disorder caused by mutations in genes on the X chromosome. In females, a mutation in one of the two copies of the gene in each cell is sufficient to cause the disorder. In males, a mutation in the only copy of the gene in each cell causes the disorder. In most cases, males experience more severe symptoms of the disorder than females.
X-linked recessive disorder
A disorder caused by mutations in genes on the X chromosome. In females, a mutation would have to occur in both copies of the gene to cause the disorder. In males, one altered copy of the gene in each cell is sufficient to cause the condition. Males are affected by X-linked recessive disorders much more frequently than females.
X‐linked myotubular myopathy
An X-linked recessive condition that primarily affects skeletal muscles and occurs almost exclusively in males. It is inherited in an X-linked recessive pattern and is caused by mutations in the MTM1 gene.