As patient advocates, your message continuity is important. Cell and gene medicine incorporates a complex lexicon that can be confusing. Within our communities, including patients, caregivers, health care providers, medical researchers and scientists, policy makers, the public and the media, there is a wide gap in knowledge and awareness about cell and gene medicine.
The ARM Foundation slide show, Understanding Cell & Gene Medicine, can be used to help different stakeholders understand the fundamentals of cell and gene medicine, including gene therapy, gene editing, cellular therapy, and regenerative medicine.
Sometimes, a disease or debilitating health condition is caused by one or more genetic changes in the body. Many diseases or conditions caused by defective genetic code have few treatment options. Conventional medicine often treats the unwanted symptoms of the disease or slows down the disease. Doctors use cell and gene medicine to try to resolve the underlying genetic defect that is causing an incurable disease or health condition.
Cell and gene medicine are part of Regenerative Medicine, which draws on insights of late 20th century cell biology, molecular biology, chemistry, computer science, bioengineering, genetics, medicine, robotics, and other fields to understand and harness the body’s repair and development mechanisms. Regenerative medicine addresses many of the most challenging health issues in medicine. Treating the genes themselves, that are the root causes of gene-based diseases and disorders, is the aim of Gene Medicine. In Cell Therapy, cells themselves are used as agents of repair or restoration of function.
Genes are regions of DNA that direct the production of proteins and direct biologically important functions throughout the body. Genes are inherited from our biological parents.
People have around 25,000 genes. We typically get two copies of each gene, one from each of our parents. These genes influence everything from the color of our hair to the power of our immune system, but genes aren’t always assembled correctly. Mutations, or errors, in genes can cause disease by failing to produce sufficient levels of a functional protein. A mutation is a change in the genetic sequence. Not all mutations have bad effects.
Genes can operate incorrectly when:
Today, technologies show promise for combatting gene-based diseases and resolving other conditions that may be reduced or reversed by cell and gene medicine. Single-gene disorders are at present thought to be more amenable to gene therapy than chromosomal or complex disorders.
Gene therapies are in development
Sickle Cell Disease
Gene Editing approaches are in Clinical Trials
Spinal Muscular Atrophy
Zolgensma & Spinraza are approved gene therapy products
A gene therapy is in clinical trial
Fragile X Syndrome
Prescription pharmaceutical medications are typically used to manage diseases, mitigate symptoms and relieve pain. The concept behind gene and cell therapy is to target the genetic cause of the disease. The goal is to rid the person of recurring symptoms, ideally after a single treatment. Gene therapy adds working genes within specific cells.
Currently, the therapies cannot be delivered as a standard type of drug available at a pharmacy. Instead, you find approved gene therapies at designated treatment centers. Gene therapies aim to treat diseases that currently have no treatments, where treatment options do not work well, or are high risk without the possibility of a cure. Gene therapy offers promise to treat rare inherited disorders. Of the 7,000 rare diseases that exist, 95 percent have no approved current treatment.
It is worth noting that gene therapy targets somatic cells, the vast majority of cells in the body. Gene Therapy does not target our reproductive or “germline” cells, our sperm or our eggs. This means that the treatment is corrective to the patient only and is not passed to the next generation.
Many diseases and health conditions may be improved by cell and gene medicine. A list of Approved Therapies is found at the end of this page.
Cell Therapy is the transfer of whole cells into a patient to replace or repair damaged tissue or cells. Cell therapy transfers healthy cells into a patient’s body to grow, replace, or repair damaged tissue for the treatment of a disease or trauma. The cells used in cell therapies may originate from the patient (autologous cells) or a donor (allogeneic cells). There are autologous therapies that have been approved for use. Kymriah, Provenge, and Yescarta for cancers.
The most common type of allogeneic cell therapy is blood transfusion, in which red blood cells, white blood cells, and pieces of cells called platelets are transferred from a donor to a patient.
If you collected your own blood and gave it back to yourself, that would be an autologous cell therapy. Sometimes before major surgery the patient is asked to ‘donate’ blood that would be used if she needed blood during the surgery.
A bone marrow transplant is a stem cell therapy. Blood forming stem cells from bone marrow are transfused from one person to another. The new blood forming stem cells divide and create all the cells in the blood – white blood cells, red blood cells, and many other types.
One goal of allogeneic cell therapy is so-called “off-the-shelf” cell therapy. The cells would be derived from a donor or donors, and prepared or manufactured in large quantities, ideally to create a treatment that could serve many patients. Allogeneic cell therapies, once demonstrated to be effective, would be manufactured and readily available to a patient.
Different types of cells can be used to create cell therapy using complex tools:
WHAT ARE STEM CELLS, A TED-EX TALK BY CRAIG A. KOHN (2013) – This is a video that gives a reasonable overview of stem cells, despite the many scientific discoveries since 2013. The video says, “using stem cells to replace bodily tissue is called Regenerative Medicine” (1:45). Regenerative Medicine encompasses other scientific tools in addition to stem cells.
In gene therapy, doctors modify a person’s genes to treat or cure disease. Human gene therapy seeks to modify or manipulate the expression of a gene or to alter the biological properties of living cells to prevent disease, reduce further damage and pain, or potentially cure the patient. Gene therapies can work by several mechanisms.Gene therapy can be done by:
If a mutated gene is causing an important protein to function poorly, gene therapy seeks to restore the function of the protein and therefore restore certain functions of the patient.
If a mutated gene causes an important cell-building protein to function poorly, gene therapy may be able to restore the function of the protein by:
Researchers select the right approach based on the best current understanding of the CAUSE of the disease. This is an important point.
Gene therapy may be performed in vivo, in which a gene is transferred to cells inside the patient’s body, or ex vivo, in which a gene is delivered to cells in a laboratory setting and the treated cells are then transferred back into the body.
Currently, gene therapy developers develop medicines to introduce new or corrected genes into patient cells using vectors. Vectors are delivery vehicles, or carriers, that encapsulate therapeutic genes for delivery to cells. Currently used vectors include disabled viruses and nonviral vectors, such as lipid particles.
Deactivated or disabled viruses cannot make patients sick, even though they rely on the biology of viruses to operate. Viral vectors are made from parts of virus and act as the vehicle to transfer new genetic material into the cell where it is incorporated into the chromosomes in the nucleus.
Deactivated viruses that have been used for human gene therapy vectors include:
In Gene-modified cell therapy, specific cells are genetically modified outside the body in order to help the patient fight a disease. After removing specific cells from the body, the cells are transferred to a laboratory where a new gene can be introduced or a faulty gene can be corrected in the cells. Therapies created this way can also be called Ex Vivo gene therapies. The modified cells then returned to the patient in order to help the patient fight a disease, for example, in Chimeric antigen receptor T-cell (CAR T-cell) therapy for cancers.
Gene-modified cell therapy includes:
Gene Editing (also called genome editing) makes targeted changes to existing DNA in genes located on the chromosomes. With gene editing, researchers can enable or disable targeted genes, correct harmful mutations, and change the activity of specific genes. Gene editing is a set of techniques that enable researchers and clinicians to rewrite the instruction encoded in the DNA of genes. These molecular-biology techniques can enable or disable targeted genes, correct harmful mutations, modify expression of genes or change activity of a specific cell, with the goal of restoring normal function. CRISPR is an example of a gene editing technique that has entered clinical trials.
DNA may be inserted, replaced, removed, or modified at particular locations in a genetic sequence for therapeutic benefit in order to treat cancer, rare inherited disorders, HIV, or other diseases. Several approaches rely on the use of molecular scissors, often an engineered enzyme, to make precise cuts at a specific location in the genome. The gap that results is then repaired, using healthy genetic material, to create a corrected gene.
Genome editing enzymes that are currently used in genome editing include:
Alternatively, genome editing can also be performed by homologous recombination of adeno-associated virus (AAV)-derived sequences into the patient’s DNA.
Homologous recombination is a type of genetic recombination that occurs during meiosis (the formation of egg and sperm cells). Paired chromosomes from the male and female parent align so that similar DNA sequences from the paired chromosomes cross over each other. Crossing over results in a shuffling of genetic material and is one reason for the genetic variation and yet similarities we see in children.
Zinc finger and CRISPR-Cas9 gene editing are also used to silence genes. Gene silencing might be used if a gene mutation is causing overproduction of a protein.
Another method to ‘turn off’ a gene is RNA interference (RNAi). Specific genes are prevented from producing protein by prevent messenger RNA (mRNA) from creating the disease-causing proteins.
Doctors use a combination of cells and bioengineered materials to restore, maintain, improve, or replace damaged tissue. Called tissue engineering, this process of restoring, maintaining, improving, and/or replacing damaged tissues and organs looks to create functional human tissues or organs in a laboratory before they are placed back into the human body.
Tissue engineering uses a combination of three key components: scaffolds, cells, and biomedical materials.
Tissue engineering often begins with a scaffold, which may utilize any of a number of potential materials from naturally occurring proteins to biocompatible synthetic polymers, to provide the structural support for cell attachment and subsequent tissue growth.
Certain tissue engineering therapies may use an existing scaffold by removing cells from a donor organ, a process called decellularization, until only the pre-existing protein-based scaffold or extracellular matrix (ECM) remains. Cells —and in some cases, additional growth factors to encourage the cells to take root— are added, allowing a tissue or organ to develop and grow ex-vivo.
Biomaterials, which include any substance engineered to interact with a patient’s living biological system for a medical purpose, often provide support as the physical structure for engineered tissues.
Researchers have successfully engineered bladders, small arteries, skin grafts, cartilage and a full trachea.
60 Seconds of Science: What is Tissue Engineering? (2016) – NIBIB Video. “Tissue Engineering, also called Regenerative Medicine, refers to the attempt to create functional human tissue from cells in a laboratory”
Regenerative medicine includes cell therapies, gene therapies, and tissue-engineered products intended to augment, repair, replace or regenerate organs, tissues, cells, genes, and metabolic processes in the body to restore or establish normal function.
Several cell and gene medicines have been approved in the United States and in Europe.
NAME OF CONDITION
LOCATION OF APPROVED USE
Tissue Engineered Medical Product Bio-scaffold material
USA, Europe, Canada, Singapore
Cancer – leukemia
CAR -T cell therapy (CD19-directed genetically modified autologous T-cell immunotherapy)
Novartis Pharmaceuticals Corporation
USA, Europe, Canada, Japan
Cancer – B Cell Malignancies
CAR -T cell therapy (CD19-directed genetically modified autologous T-cell immunotherapy)
Kite Pharma, Incorporated
USA, Europe, Canada
Gene therapy (Adeno-associated virus vector-based gene therapy)
Spark Therapeutics, Inc.
Cartilage defects in the knee
Tissue engineered medical product — Autologous cellularized scaffold product
Autologous Cultured Chondrocytes on a Porcine Collagen Membrane
Tissue Engineered medical product — autologous keratinocytes
Cultured Epidermal Autografts
Cancer – Prostate cancer
Autologous cellular immunotherapy
Autologous Cellular Immunotherapy
Cancer – melanoma
Gene therapy directed at the tumor itself
Spinal Muscular Atrophy
Oral soft tissue
Tissue engineered medical product – Allogeneic cellular sheet with other factors
Spinal Muscular Atrophy
Autologous cellular product
Fibrocell Technologies, Inc.
Diabetic Foot ulcers
tissue engineered medical product — Bilayer dermal regeneration matrix
bilayer matrix for dermal regeneration
ELF, the Every Life Foundation
NORD, the National Organization for Rare Disorders
Academic and research societies:
ASGCT, American Society of Gene & Cell Therapy
ISCT, International Society for Cell & Gene Therapy
Information for people considering clinical trials
CISCRP, Center for Information and Study on Clinical Research Participation
Industry and policy: