DEFINITION OF TERMS
ADENOVIRUSVirus belonging to the family Adenoviridae of DNA viruses having a nonenveloped virion with 252 capsomeres and a diameter between 70 and 90 nm; a single linear molecule of double-stranded DNA (36 to 38 kb); at least 10 structural ether-resistant and acid-stable proteins; virions are released by cell destruction.
ADENOVIRUS-ASSOCIATED VIRUS (AAV)Human parvovirus contains a single-stranded DNA genome and depends on helper viruses (adenovirus, herpesvirus, or vaccinia-virus) for replication. Without coinfection, the wild-type virions integrate at a specific site on chromosome 19 and remain latent.
ADVENTITIOUS AGENTA foreign substitute that is introduced accidentally or inadvertently; not natural or hereditary (as in microbial, chemical, or biochemical contamination of a purified substance).
ALLOGENEICFrom an unrelated member of the same species; from the same species, but with a different genotype.
AMPHOTROPIC VIRUSA virus that infects and replicates in cells from multiple species.
ANCILLARY PRODUCTSComponents used during manufacturing that should not be present in the final product. Examples: growth factors, cytokines, monoclonal antibodies, cell separation devices, media, and media components.
ANTISENSE THERAPYThe use of antisense oligonucleotides (a complementary segment to RNA) to control or inhibit gene expression.
APHERESISProcedure of withdrawing blood from a donor, removing select components (e.g., platelets or leukocytes), and retransfusing the remainder into the donor.
AUTOLOGOUSFrom one's own body.
BASE PAIRTwo nucleotide bases on different strands of the nucleic acid molecule that bond together.
BIOASSAYMeasurement of the effectiveness of a compound by its effect on animals or cells in comparison with a standard preparation. (See also Potency.)
BIOLOGICAL PRODUCTAny virus, therapeutic serum, toxin, antitoxin, or analogous product applicable to the prevention, treatment, or cure of diseases or injuries in humans. (The term analogous product has been interpreted to include essentially all biotechnology-derived products and procedures including gene therapy, transgenics, and somatic cell therapy.)
BIOTECHNOLOGYAny technique that uses living organisms (or parts of organisms) to make or modify products, to improve plants or animals, or to develop microorganisms for specific uses. The newer definition refers to the industrial and pharmaceutical use of rDNA, cell fusion, novel bioprocessing techniques, and gene therapy.
B LYMPHOCYTES (B cells)A class of lymphocytes that produce antibodies and are derived from the bone marrow.
BONE MARROW CELLSA variety of undifferentiated cells (stem cells) and differentiated cells (lymphocytes, granulocytes, erythrocytes, and platelets) found in the internal cavities of bones or bone marrow.
BONE MARROW TRANSPLANTATIONTransplantation of bone marrow cells that are capable of maintaining the hematological functions indefinitely. Technique used in the treatment of immunological disorders (severe combined immune deficiencies such as ADA deficiency), hematological disorders (anemia), metabolic disorders (Gaucher's disease), and malignant diseases (leukemia, lymphoma, or solid tumor).
CD34Cluster of Differentiation cell-surface marker 34. CD34 is a protein that distinguishes stem and progenitor cells from more mature blood cells.
CELL LINESCells that are derived from primary culture embryos, tissue, or organs. Such cell lines may have a finite life span or be immortalized (made to replicate indefinitely).
CELL THERAPYTherapy that uses whole cells to treat a disease, condition, or injury.
CGMPCurrent good manufacturing practice. The FDA outlines CGMP in the 21 CFR and in the Federal Register and its Points to Consider.
CHONDROCYTESCells that produce the components of cartilage.
CLONALGenes, cells, or entire organisms derived from and genetically identical to a single common ancestor gene, cell, or organism.
CLONOGENIC ASSAYProcedure based on the ability to give rise to a clone of cells.
COMPLEMENTARY DNA (cDNA)DNA synthesized from an mRNA rather than a DNA template. It is used for cloning or as a DNA probe for locating specific genes.
CYTOKINEAny factor that acts on cells; usually a protein that promotes growth.
CYTOPLASMCellular material that is within the cell membrane and surrounds the nucleus.
CYTOTOXICAble to cause cell death.
DENDRITIC CELLCells that sensitize T cells to antigens.
DIFFERENTIATIONA process of biochemical and structural changes by which cells become specialized in form and function.
DIPLOID CELLA cell with two complete sets of chromosomes (see Haploid Cell).
ECOTROPIC VIRUSA virus that infects and replicates in cells from only the original host species.
ELECTROPORATIONPhysical means of gene transfer (using a brief electrical field), involving creation of temporary pores in cell membrane to introduce DNA.
ELISAEnzyme-linked immunosorbent assay. An immunoassay that utilizes an enzyme-labeled antigen or antibody to detect the binding of a molecule to a solid matrix.
ENDOTHELIAL CELLS Epithelial cells of mesodermal origin that line the internal cavities of the body, such as heart and blood and lymph vessels.
ENGRAFTMENTProcess whereby cells, tissues, or organs are implanted or transplanted into another organism. Refers both to the mechanical and the biological processes necessary to have a fully functional graft.
ENVELOPED VIRUSESViruses containing a lipoprotein bilayer surrounding the capsid and acquired by budding through the cell membrane of the host cells.
EPIDERMALPertaining to the outermost and nonvascular layer of the skin derived from embryonic ectoderm.
EPISOMALPertaining to any accessory extrachromosomal genetic material.
EPITHELIAL CELLSCells from the linings of various organs. Examples: respiratory, intestinal, or vascular epithelial cells.
EXTRACORPOREALSituated or performed outside of the body.
EX VIVOProcedure performed outside of the living organism.
FIBROBLASTSConnective tissue cells that have the capacity to produce collagen.
FLUORESCENCE-ACTIVATED CELL SORTER (FACS)A machine that sorts cells based on fluorescent markers attached to them.
FORMULATEDPrepared in accordance with a prescribed method or conditions.
FUSIONJoining of the membrane of two cells, creating a daughter that contains some of the same properties from each parent cell. It is used in making hybridoma cells in which antibody-producing cells are fused to mouse myeloma cells.
G-418The antibiotic used to select and isolate cells that contain neomycin-resistance gene.
GENE CONSTRUCTExpression vector that contains the coding sequence of the protein and the necessary elements for its expression.
GENE THERAPYTherapy that uses DNA to treat a disease or condition. FDA defines gene therapy products as products containing genetic material administered to modify or manipulate the expression of genetic material to alter the biological properties of living cells.
GENOMETotal hereditary material of a cell.
GERM CELLReproductive cell (sperm or egg), gamete, or sex cell.
GRAFT VERSUS HOST DISEASE (GVHD)Rejection of the transplanted tissue by the host. It is the leading cause of patient death when mismatched allogeneic tissue is used.
GRAFT VERSUS LEUKEMIA (GVL)Rejection of host leukemia cells by donor T cells.
GRANULOCYTEOne of three types of white blood cells. These cells digest bacteria and other parasites.
GRANULOCYTEMACROPHAGE COLONY-STIMULATING FACTOR (GM-CSF)A natural hormone that stimulates white blood cell production, particularly that of granulocytes and monocytes.
GROWTH FACTORSFactors responsible for regulatory cell proliferation, function, and differentiation.
HAPLOIDA cell with half the usual number of chromosomes or only one chromosome set. Germ cells are haploid.
HELPER VIRUSAids the development of a defective virus by supplying or restoring the activity of a viral gene or by enabling the defective virus to form a functional envelope.
HEMACYTOMETERA device used to manually count cells.
HEMATOPOIETICPertaining to or affecting the formation of blood cells.
HEPATOCYTESThe predominant cell type in the liver that has an important role in metabolism and is a source of serum proteins. These cells are generally not dividing, but when injured they can divide and regenerate until the injured cells are replaced.
HERPES SIMPLEX VIRUS (HSV)A DNA virus that is a member of the family Herpesviridae. It can infect both warm- and cold-blooded vertebrates by contact between moist mucosal surfaces.
HUMAN LEUKOCYTE ANTIGEN (HLA)Proteins controlled by the major histocompatibility complex. These proteins play a key role in determining transplant compatibility.
HUMORALPertaining to elements found in body fluids (for example, humoral immunity and neutralizing antibodies).
HYBRIDIZATION DOT BLOT (DNA or RNA)A technique for detecting, analyzing, and identifying protein; similar to the Western blot but without electrophoretic separation of proteins.
IMMUNOASSAYTechnique for identifying substances based on the use of antibodies.
IMMUNOFLUORESENCETechnique for identifying a fluorescent label.
IMMUNOGENSubstance capable of inducing an immune response; a form of antigen that induces immune response, as opposed to a tolerogen that induces tolerance.
IMPLANTATION VS TRANSPLANTATIONImplantation is the insertion or grafting of a biological, living, inert, or radioactive material into the body. Transplantation is the grafting of tissues from the patient's own body or from another person's body.
INSERTIONAL MUTAGENESISA type of mutation that is caused by the insertion of a foreign gene into a host-cell chromosome. There are multiple negative consequences of such an event, including death of a cell if an essential gene is inactivated or predisposition to cancer if a tumor suppressor gene is inactivated.
INTEGRATIONAssimilation of genetic material (DNA) into the chromosome of a recipient cell.
INTERLEUKIN (IL)Lymphokine that regulates the growth and development of white blood cells. More than 12 have been identified.
INTRABODIESIntracellular antibodies that are not secreted and that are designed to bind and inactivate target molecules inside cells.
IN VIVOProcedure performed in the living organism.
IN VITROProcedure performed outside of the living organism. It may involve cells or tissues derived from the organisms.
-islet cells of the pancreas that secrete insulin.
ISOGENICOf the same genotype.
KERATINOCYTESDifferentiated epidermal cells that constitute the top layer of cells in the skin.
LEUKEMIAMalignant neoplasm of the blood-forming tissues.
LINEAGE (COMMITTED PROGENITOR CELLS, DIFFERENTIATED CELLS)Specific path of cell differentiation that can be traced to a single cell of origin.
LIPOPLEXA formulation of lipids and polymers and/or proteins.
LIPOSOMEA spherical lipid bilayer enclosing an aqueous compartment.
LYMPHOKINEClass of soluble proteins produced by white blood cells that play a role in the immune response.
LYMPHOMAForm of cancer that affects the lymphatic tissue.
MICROINJECTIONPhysical means of gene transfer involving a direct injection of the cell with a syringe and a needle.
MACROPHAGEAny of many forms of mononuclear phagocytes that are found in tissues and arise from hematopoietic stem cells in the bone marrow.
MOCK RUNA test run that deliberately omits some critical reagents.
MONOCLONAL ANTIBODIESAntibodies that are derived from a single cell clone.
MONOCYTESOne of the three types of white blood cells. They are precursors to macrophages.
MYELOSUPPRESSIONInhibition of bone marrow activity resulting in depletion of red cells, white cells, and platelets.
MYOCYTESFundamental cell units in the muscle. Target cells for insertion of genes that encode secretory proteins.
NEOMYCINAntibiotic derived from Streptomyces fradiae.
NAKED DNAIsolated, purified, and uncomplexed DNA (no protein or lipid).
OLIGONUCLEOTIDEA polymer consisting of a small number of nucleotides, usually 5 to 30.
ONCOGENESGenes associated with neoplastic proliferation (cancer) following a mutation or perturbation in their expressions.
OSTEOGENIC CELLSDerived from or involved in the growth or repair of bone.
PACKAGING CELL LINECell line that produces all of the proteins required for packaging and production of viral vectors in an active form, but does not produce replication-competent virus.
p53 GENEGene whose mutation is the most common alteration observed in human cancers. It is not required for normal development, but the lack of this gene highly increases the potential risk of cancer.
PARVOVIRUSDNA viruses of the family Parvoviridae. Host range includes many vertebrate species.
PERCUTANEOUSPerformed through the skin. An example of a percutaneous procedure is the injection of an agent or removal of a tissue (sample for biopsy) with a needle.
PERITONEAL MESOTHELIUMLining of the peritoneal cavity consisting of a single sheet of cells covering a broad surface. It has abundant lymphatic drainage and permits diffusion of macromolecules.
PLASMIDA small circular form of DNA that carries certain genes and is capable of replicating independently in a host cell.
POLYCLONALDerived from a population of cells consisting of many clonal types.
PROCESS VALIDATIONMeans for providing documentation that the manufacturing process is controlled, reproducible, and capable of consistently producing a product that meets predetermined specifications.
PRODUCER CELL LINEAn established cell line used to produce virus vectors, often at a large scale.
POLYMERASE CHAIN REACTION (PCR)Technique to amplify a target DNA or RNA sequence of nucleotides by several hundred thousand-fold.
POTENCYA quantitative measure of biological activity based on the attribute of the product linked to the relevant biological properties.
PROGENITOR CELLParent or ancestral cell, usually one that is already committed to differentiate into a specific type or lineage of cells.
PROMOTERDNA sequence that is located at the front of a gene and controls gene expression. It is required for binding of RNA polymerase to initiate transcription.
RADIOIMMUNOASSAY (RIA)Technique for quantifying a substance by measuring the reactivity of radioactively labeled forms of the substance.
RECOMBINANT-DNADNA produced by joining fragments of DNA from different sources by in vitro manipulations.
REPLICATION-COMPETENT VIRUSA virus that can complete an entire replication cycle without a need for a helper virus; an autonomously replicating virus.
RESTRICTION ENDONUCLEASEAn endonuclease that recognizes a specific sequence of bases within double-stranded DNA.
RETROVIRUSA virus that contains the reverse transcriptase, which converts viral RNA into DNA that then integrates into the host cell in a form called a provirus.
SERUM-FREERefers to cell growth medium that lacks a serum component.
SOMATIC CELLSCells other than the germ cells.
S PHASEPart of the cell cycle during which DNA replication occurs.
STEM CELLImmortal cell that is capable of proliferating and differentiating into different types of specialized cells. Each major tissue system is thought to have its own putative stem cell.
STROMALRefers to cellular support elements that contain essential nutrients or growth factors.
SUPRAVITAL DYEA dye that stains only living cells.
SUSPENSION CULTURECells capable of growth in suspension, not requiring substrate (attachment) on which to grow.
T CELLSLymphocytes that acquire functional repertoires and the concept of self in the thymus and are responsible for cell-mediated immunity. There are several subsets of T cells (helper T cells, suppressor T cells, and cytotoxic T cells).
TCID 50 ASSAYTissue Culture Infectious Dose, 50% Assay. An assay measuring the amount of product at which 50% of culture cells in the assay are killed (cytopathic effect) or are expressing a vector protein.
TRANSDUCTIONTransfer and expression of genetic material into a cell by means of a virus or phage vector.
TRANSFECTIONTransfer of DNA into cells by physical means such as by calcium phosphate coprecipitation.
TRANSGENERefers to the foreign or therapeutic DNA that is part of a vector construct.
TUMORGENICITYHaving the properties of inducing a malignant neoplasm.
VECTORThe agent (plasmid, virus, or liposomeprotein or DNAprotein complex) used to introduce DNA into a cell.
VIABILITYState of being alive and functional.
VIRIONAn elementary viral particle consisting of genetic material (nucleocapsid) and a protein covering.
VIRUSSubmicroscopic organism that contains genetic information necessary for reproduction. It is an obligate intracellular parasite.
WESTERN BLOTAn electroblotting method in which proteins are transferred from a gel to a thin, rigid support (e.g., nitrocellulose membrane) and detected by binding radioactively labeled antibody or antibody coupled to an enzyme, allowing use of a precipitating chromogenic or chemiluminescent substrate.
XENOGENEICFrom a different species.
XENOTRANSPLANTATIONTransplantation of organs from one species to another (e.g., from pigs to humans).
ZOONOSISThe disease of animals transmitted to humans via routine exposure to or consumption of the source material.