XXVI Congress

59 days

6 hours

12 mins

What is gene and cell therapy?

Gene and cell therapy is the use of genes and cells to treat disease. A gene is the unit of DNA that contains hereditary information that is passed down from generation to generation. All genes together are called the genome. Genes may contain information about visible traits, such as height or eye colour. Many genes contain the instructions for RNA or protein molecules that are not visible from the outside, but perform important functions in the body's cells. Cells are the building blocks of plants and animals (including humans). They are small functional units that work together to form organs and tissues.

Genetic diseases are caused by errors, or mutations, in genes that result in a loss or change of function of  RNA or protein molecules. These mutations can be passed down from parents to children or can happen spontaneously. Humans have two copies of each gene, one inherited from their mother and one inherited from their father. Dominant mutations cause disease when only one of the copies has the mutation, while recessive mutations only cause disease if both copies are affected by the mutation. As long as an individual has one healthy copy (scientists call this wild type) of a recessive gene, they will be healthy. We call these individuals carriers. This explains why in some families some children (those with two copies of the mutation) are ill, while others (those with one wild type and one mutated copy) are healthy carriers.

Video from the US Food and Drug Administration (FDA)

Gene therapy is the use of genetic material to treat genetic diseases. This may involve adding a wild type copy of the gene (gene addition) or altering a gene with mutation to the wild type gene (gene editing). The treatment may take place outside of the body (ex vivo) or inside the body (in vivo). To get the gene into the genome inside the cells, modified viruses or other vectors are used.

Cell therapy is the use of cells that are taken either from the patient themselves or a donor to treat diseases. Cells used for cell therapy are often stem cells, cells that can mature into different types of specialised cells. Cells used for cell therapy may or may not be genetically altered. It is sometimes easier to remove cells from the body, treat them with gene therapy and then place them back than treating the cells inside the body. This is the case for gene therapy for blood disorders. Gene and cell therapy therefore often go together, which is reflected in the name of our society.

For more information on stem cells, please see the EuroStemCell website. Further informative videos about gene therapy include those by gene therapy companies AGCT and bluebird bio.

Current developments in gene and cell therapy

All medicines and treatments go through stringent testing in the lab (pre-clinical research) and in small groups of patients (clinical research). Enormous progress has been made in gene and cell therapy research since the the 1970s and 1980s. The first clinical successes in patients were in the 1990s and the first treatments were approved for general use in the past decade. Gene and cell therapy products approved for use in patients now include: Glybera, Strimvelis, Yescarta, Kymriah.

Gene and cell therapy technology is evolving rapidly and we are now closer than ever to gene and cell therapies for many different diseases. However, gene and cell therapies remain experimental medicines and much more research is needed before many of these therapies are available to all patients everywhere.

Some developments that have been crucial for gene and cell therapies are gene editing (particularly CRISPR, which is more efficient and more precise than zinc finger nucleases and TALENs), induced pluripotent (iPS) cells and safer viral vectors for gene delivery.

For more information on gene editing, please see this video from the Royal Society. More information on iPS cells is available on the EuroStemCell website.

Clinical trials

Clinical trials are an extremely important part of research. In taking part in a clinical trial a patient is informing future treatment of the disease they suffer from and may gain early access to potential treatments. However, the treatments are not guaranteed to work and there may be risks involved in taking part in a clinical trial. We recommend that you discuss the potential risks and benefits with a trusted qualified physician before enrolling in a clinical trial.

For more information on regulation of medicines, please see the EMA website (EU) and the FDA website (USA). Current clinical trials are listed on the EU Clinical Trials Register and ClinicalTrials.gov (USA).

Patient perspective

In 2017 we celebrated our 25th anniversary as a society. To illustrate the progress that gene and cell therapy has made since ESGCT was founded in 1992, we made made an overview of patients who have been treated with these therapies and the effect this had on their lives.

Our members and others all over the world work hard everyday to change many more lives over the next 25 years and beyond. Many disorders for which gene therapies are being developed have patient organisations. Patient organisations are often involved in patient advocacy and providing information and peer support. They may also be involved in research or fundraising for research. Most patient organisations can be easily found through their websites and social media presence and some can be found on our Gene and Cell Therapy Community Heatmap.

Gene and cell therapy glossary

Allele - A variant form of a gene at a particular Locus on a chromosome. Different alleles produce variations in inherited characteristics.

Autologous transplant—Transplanted tissue or cells derived from the intended recipient of the transplant themselves. Such a transplant helps to avoid the body attacking the transplanted tissue or cells (immune rejection). For example, blood stem cells that are isolated from a patient and then placed back with or without a genetic change.

Cas9 (CRISPR Associated Protein 9) - A specialised enzyme known as a nuclease that has the ability to cut DNA sequences. Cas9 makes up part of the “toolkit” for the CRISPR/Cas9 method of gene editing.

Cell - The basic building block of all living things.

Cell therapy - The use of (stem) cells in regenerative medicine to replace defective, damaged, or missing tissue.

Chromatin - The complex of DNA and proteins that forms chromosomes. Some of the proteins are structural, helping to organise and protect the DNA, while others are regulatory, acting to control whether genes are active or not, and to promote DNA replication or repair.

Chromosome - A thread-like structure that contains a single length of DNA, usually carrying many hundreds of genes. This is packaged with proteins to form chromatin. The DNA within the complete cellular set of chromosomes (23 pairs in humans) comprises two copies of the genome, one from each parent. The chromosomes usually reside in the nucleus of a cell, except during cell division when the nuclear membrane breaks down and the chromosomes become condensed and can be visualised as discrete entities.

Clinical application - The use of a biomedical reagent, procedure, or device to treat a clinical condition.

Clinical trial - A supervised and monitored experimental test in patients of a newly developed clinical application to ensure minimisation of risk and optimisation of efficacy. Clinical trials are required before a treatment is approved for general use.

CRISPR (Clustered Regularly-Interspaced Short Palindromic Repeats) - A naturally occurring mechanism found in bacteria that involves the retention of fragments of foreign DNA, providing the bacteria with some immunity to viruses. The system is sometimes referred to as CRISPR/Cas9 to denote the entire gene-editing platform in which RNA homologous with the targeted gene is combined with Cas9 (CRISPR Associated Protein 9), which is a DNA-cutting enzyme (nuclease) to form the “toolkit” for the CRISPR/Cas9 method of gene editing.

Cultured cell - A cell maintained in a tissue culture allowing expansion of its numbers.

Deoxyribonucleic acid (DNA) - A two-stranded molecule, arranged as a double helix, that contains the genetic instructions used in the development, functioning, and reproduction of all known living organisms.

Differentiation - The process whereby an unspecialised stem or progenitor cell acquires the features of a specialised cell, such as a heart, liver, or muscle cell.

Diploid - Cells that contain a full set of DNA—half from each parent. In humans, all cells apart from germline cells are diploid and they contain 46 chromosomes (in 23 pairs).

Dominant - A pattern of inheritance of a gene or trait in which a single copy of a particular allele (gene variant) confers a function independent of the nature of the second copy of the gene in a diploid cell of an organism.

Double-strand break (DSB) - A break in the DNA double helix in which both strands are cut, as distinct from a single-strand break or “nick.”

Endogenous - Originating from within a cell or an organism.

Enzyme - A protein that acts as a biological catalyst, speeding up chemical reactions.

Ex vivo - Latin: “out of the living”; outside an organism.

Exogenous - Introduced or originating from outside a cell or an organism.

Gain of function - A type of mutation that results in an altered gene product that possesses a new molecular function or a new pattern of gene expression.

Gene - A functional unit of heredity that is a segment of DNA in a specific site or Locus on a chromosome. A gene typically directs the formation of a protein or RNA molecule.

Gene editing - The process of altering the DNA by inserting, deleting, or modifying a gene. Sometimes referred to as genome editing or genome engineering.

Gene expression - The process by which RNA and proteins are made from the instructions encoded in genes. Gene expression is controlled by proteins and RNA molecules that bind to DNA or RNA and regulate the levels of production of their products. Alterations in gene expression change the functions of cells, tissues, organs, or whole organisms.

Gene therapy - Introduction of exogenous genes into cells with the goal of curing or improving a disease condition.

Gene transfer - Any process often used to describe the transfer of genes into cells—as used in gene therapy.

Genome - The complete set of DNA that makes up an organism. In humans, the genome is organised into 23 pairs of homologous chromosomes.

Genome editing - The process by which the genome sequence is changed through the intervention of a DNA break or other DNA modification.

Genotype - Genetic constitution of an individual.

Germline cell (or germ cell) - A cell that will give rise to sperm or eggs. Modifications in the germline continue into the next generation, as opposed to modifications in somatic cells.

Guide RNA (gRNA) - Short segments of RNA used to direct the DNA-cutting enzyme to the target location in the genome. gRNA segments contain the region of homology to the target sequence (usually 20 bases), and a sequence that interacts with the nuclease (e.g., Cas9). gRNAs used in genome editing are synthetic and do not occur in nature.

Heterozygous - Having two different variants (alleles) of a specific gene on the two homologous chromosomes of a cell or an organism.

Homologous recombination - Recombining of two like DNA molecules, including a process by which gene targeting produces an alteration in a specific gene.

Homology-directed repair (HDR) - A natural repair process used to repair broken DNA, which relies on a DNA “template” with homology to the broken stretch of DNA. This usually occurs during or after DNA synthesis, which provides this template. In gene editing via HDR, the DNA template is synthesised or made by recombinant DNA techniques, and usually contains regions of exact homology to the target Locus at each end, with the desired alteration contained within the middle.

Homozygous - Having the same variant (allele) of a specific gene on both homologous chromosomes of a cell or an organism.

In vitro - Latin: “in glass”; in an artificial environment, such as a laboratory dish or test tube.

In vivo - Latin: “in the living”; in a natural environment, usually in the body.

Indel - An insertion or deletion of DNA. Small indels (e.g., one to four nucleotides) are often associated with non-homologous end joining. These often result in the disruption of a gene by shifting the open reading frame and/or creating premature stop codons.

Insertional mutagenesis - The alteration of the sequence of a gene by the insertion of exogenous sequence such as by integration of viral sequences.

Locus - An area of location on a chromosome.

Loss of function - A type of mutation in which the altered gene product (RNA or protein) lacks the molecular function of the wild-type gene.

Mitochondrial transfer (or mitochondrial replacement) - Novel procedures designed to prevent the maternal transmission of mitochondrial DNA (mtDNA) diseases.

Mitochondrion (plural, Mitochondria) - A cellular structure in the cytoplasm that provides energy to the cell. Each cell contains many mitochondria. In humans, a single mitochondrion contains 37 genes on a circular mitochondrial DNA, compared with about 35,000 genes contained in the nuclear DNA.

Mutation - A change in a DNA sequence. Mutations can occur spontaneously during cell division or can be triggered by environmental stresses, such as sunlight, radiation, and chemicals.

Nonhomologous end joining (NHEJ) - A natural repair process used to join the two ends of a broken DNA strand back together. This is prone to errors where short indels (usually of two to four base pairs of DNA) are introduced.

Nuclease - An enzyme that can cut through DNA or RNA strands.

Nucleotide - Building block of DNA and RNA. Can be one of four, adenine (A), cytosine (C), guanine (G), thymine (T). In RNA, uracil (U) is the equivalent of thymine. Also known as "base", which form "base pairs" in which A binds to T and C binds to G to form one rung on the DNA double helix.

Off-target effect - A direct or indirect, unintended, short- or long-term consequence of an intervention on an organism other than the intended effect on that organism.

Organism - A living being, such as a microbe, plant or animal (including humans).

Phenotype - Observable properties of an organism that are influenced by both its genotype and its environment.

Plasmid - A self-replicating circular DNA molecule. A plasmid can be engineered to carry and express genes of interest in target cells.

Preclinical research - Research conducted to investigate potential clinical applications but not involving humans. For example, research on molecules, cells, tissues, or animals.

Precursor cell or progenitor cell - In foetal or adult tissues, it is a partially committed but not fully differentiated cell that divides and gives rise to specialised, differentiated cells.

Protein - A large complex molecule made up of one or more chains of amino acids. Proteins perform a wide variety of activities in the cell.

Recessive - A recessive allele of a gene is one whose effects are masked by the second allele present in a diploid cell or organism, which is referred to as dominant.

Regenerative medicine - Medical treatments that seek to replace defective, damaged, or missing tissue by engineered cells, tissues, or implants, often involving stem cells.

RNA (ribonucleic acid) - A chemical that is similar in structure to DNA. One of its main functions is to be the intermediate molecule in the translation of the genetic code of DNA into structural proteins.

Somatic cell - Latin: soma = body; Any cell of a plant or animal other than a reproductive cell or reproductive cell precursor.

Stem cell - An undifferentiated, nonspecialised cell that can renew itself indefinitely and can differentiate to yield more mature cells with specialised functions.

  • Adult stem cells - undifferentiated cells found in a differentiated tissue in an adult organism that can renew itself and can differentiate to yield specialised cell types of the tissue in which it is found
  • Embryonic stem (ES) cells - primitive (undifferentiated) cell from the embryo that has the potential to become a wide variety of specialized cell types (pluripotent). An embryonic stem cell is not an embryo; by itself, it cannot produce the all necessary cell types to give rise to a complete organism
  • Induced (iPS) cells - cells that have acquired stem cell-like properties by the introduction or activation of genes. This is useful in regenerative medicine because the iPS cells can be introduced back into the donor of the original cells with much less risk of transplant rejection.

T cells - Types of white blood cells that are of crucial importance in the immune system. They cooperate with other immune cells in killing infected or cancerous cells but can also participate in inflammation or in autoimmunity when they become activated against an organism's own cells or tissues.

Transcription - Making an RNA copy from a gene or other DNA sequence. Transcription is the first step in gene expression.

Transcription Activator-Like Effector Nuclease (TALEN) - A class of engineered restriction enzymes generated by the fusion of a transcription activator-like effector DNA-binding domain (that binds to a specific DNA sequence) to a DNA-cleavage domain (nuclease) to be used as a gene-editing tool (adapted from NASEM, 2016a, p. 186). TALENs followed zinc finger nucleases and preceded CRISPR/Cas9 as gene-editing tools.

Transcription factor - A protein that binds to control regions of genes to activate or repress their transcription (or expression).

Transfection - A method by which experimental DNA may be introduced into a cell.

Transgene - A gene that has been introduced into a cell or organism. Transgenes can be integrated at random, or targeted to a specific site by homologous recombination or by gene editing using methods of homology-directed repair.

Translation - The process of forming a protein molecule from information contained in a messenger RNA —a step in gene expression following transcription (copying of RNA from DNA).

Variant - Genes have many variants in a population that can differ somewhat in function, some being advantageous and some being deleterious or non-functional. The differences in the gene may be as small as a single nucelotide. These single nucleotide variants are also known as SNPs (single nucleotide polymorphisms).

Vector - A vehicle that transfers a gene into a new site. Vectors used in molecular cell biology, gene editing and gene therapy include plasmids and modified viruses engineered to carry and express genes of interest in target cells. The most clinically relevant viral vectors for gene transfer include retroviral, lentiviral, adenoviral, and adeno-associated viral vectors.

Wild type (noun); Wild-type (adjective) - The “normal” type of an organism or a gene.

Zinc finger - A small protein structure based on naturally occurring transcription factors that bind to defined DNA sequences to control the activity of nearby genes. Zinc fingers can be custom engineered to target a specific section of the DNA sequence for use in genome engineering.

Zinc finger nuclease (ZFN) - A class of engineered enzymes generated by the fusion of zinc finger DNA-binding domains to an enzyme that cuts DNA that can be used as a gene-editing tool.

Gene and cell therapy glossary dapted from Human Genome Editing: Science, Ethics, and Governance, doi: 10.17226/24623