Understanding Cell and Gene Medicine - Guidance - Healing Genes
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A Guide to Understanding Cell and Gene Medicine

Ethnic young adult female cancer patient hugged by her mother

Introduction to Cell & Gene Medicine

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.

Talking to the General Public about Cell and Gene 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.

Understanding Genes and Defective Genes

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.

  • DNA is the name of a molecule.
  • Each DNA molecule is made up of a sequence of building blocks called nucleotides and there are only 4, known by the letters A G C and T.
  • On the rungs of the famous double helix, the DNA molecules are paired, A with T and G with C
  • A gene is a specific sequence of DNA molecules that act as the instructions for making protein. The Specific sequence of the DNA is called the Genetic Sequence .
  • The genetic sequence is written out as letters like TGCATTG, or GATTACA.

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:

  • inherited mutations pass from parents to babies
  • when 2 recessive disease causing genes are received from 2 parents
  • when one dominant disease-causing gene is received from one parent in eggs or sperm
  • a gene mutation occurs as the cells are replicating
  • a gene mutation occurs as the chromosomes are dividing in half during the creation of eggs or sperm
  • age causes mutations (changes) over time
  • the genes are damaged by chemicals and radiation, or other environmental toxins. For example, Skin cancer is one disease caused by long-term changes to cells after too much exposure to sunlight’s ultraviolet radiation.
  • Other gene mutations can occur when a piece of genetic code is missing, defective, or duplicated in error during pregnancy. Larger mutations can affect many genes on one chromosome. Defective genes can result in a disease or medical disorder.

Introduction to Cell and Gene Medicine

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.



Cystic Fibrosis

 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

Huntington Disease

 A gene therapy is in clinical trial

Fragile X Syndrome



FAQ: What is the difference between traditional prescription drug therapy and gene and cell therapy?

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 Therapies or Cellular Therapies

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:

  • Embryonic stem cells, pluripotent stem cells derived from embryos not needed after In Vitro Fertilization (IVF)
  • Induced pluripotent stem cells (iPSC), derived from skin or blood cells that have been reprogrammed so they become stem cells.  The cells can be guided to develop into specific human cells needed for therapeutic purposes.
  • Hematopoietic stem cells (HSCs),  stem cells responsible for refreshing our supply of healthy blood cells; they can produce billions of new blood cells each day.
  • Cord blood cells.  Cord blood is the blood left over in the umbilical cord and placenta after a baby is born.  It can be collected and stored for future use.  The primary source of stem cells in cord blood are hematopoietic stem cells (HSCs).  These cells are the building blocks of our blood and immune system. They can be used in the treatment of blood cancers such as leukemias and lymphomas, and disorders such as sickle cell disease and Wiskott-Aldrich syndrome. Additional uses for umbilical cord blood and tissue are currently under investigation.  The therapeutic use of cord blood in the United States is regulated by the FDA. Cord blood is not a cure-all.  You can learn more here.
  • Mesenchymal stromal cells – sometimes called mesenchymal ‘stem cells,’ or MSCs, these are cells that differentiate into the body’s connective tissues, blood, lymphatic system, bone, and cartilage.
  • Immunotherapy cells
    • Natural Killer (NK) cells
    • Lymphocytes
    • Dendritic cells
    • CAR-T cells, Autologous cells (cells from the patient) that are specially treated and reinfused to eradicate a patient’s cancer.  Two approved CAR-T therapies are available in the US Yescarta and Kymriah.
    • Lymphocytes are white blood cells that launch the body’s initial immune response. They are found in the circulation system, lymph nodes, tonsils, and spleen.
    • Dendritic cells:  Cells responsible for the initiation of adaptive immune responses that allow the body’s immune system to fight against damage.
  • Other types of cells
    • Epithelial stem cells:  Cells that form the surfaces and linings of the body
    • Retinal Progenitor Epithelial cells are stem cells for the retina.  Transplant of RPE is being tested as a cure for blinding retinal disease.
    • Neural progenitor cells are the cells that give rise to the various cells of the central nervous system, comprised of the brain and the spinal cord  They are being tested for repair of trauma to the spinal cord or peripheral nerves.
    • Pancreatic islet cells are clusters of cells inside the pancreas that produce insulin, the hormone required to move glucose (sugar) into cells for energy.  Islet cells in a well-functioning pancreas contain cells that produce the hormones necessary for metabolic regulation. Transplant of islets is a proven therapy for Diabetes Type 1, unfortunately, their effect when transplanted is not forever, and the supply of islets is limited.
    • Skeletal muscle stem cells. Muscle stem cells are adult stem cells in skeletal muscle tissue which can self-renew and are create new skeletal muscle cells. In healthy bodies, these stem cells are activated in response to muscle injury to regenerate damaged muscle tissue.

How to Learn More

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.

Closer Look at Stem Cells (Website)

A Patient Handbook on stem cell therapies – in six languages

Brochure (6 pages)

Gene Medicine or Gene Therapy

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:

  • Replacing a mutated (defective) gene with a healthy copy
  • Introducing a new gene to the body
  • Inactivating or “silencing” a gene that doesn’t function properly

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:

  • Replacing a disease-causing gene with a healthy copy of the gene.
  • Inactivating a disease-causing gene that is not functioning properly.
  • Introducing a new or modified gene into the body to help treat a disease

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:

  • Lentiviral vectors: A Lenti- vector can integrate its genome into both dividing and non-dividing cells in the body, leading to new gene expression that is designed to be stable and durable. Lentivectors can carry genetic information into the nucleus of cells, potentially allowing for stable and durable expression of the genetic information that it integrated into the cells.
  • Adeno-associated virus (AAV): These viruses are small single-stranded DNA viruses grouped with parvoviruses. One parvovirus causes a rash in children known as “fifth disease.”  Nevertheless, AAVs are a different class of parvoviruses and they are dependent on a helper virus co-infection to replicate. Viruses that have difficulty replicating make them better candidates to use to create vectors.
  • Adenoviruses: Adenoviruses is a group of common viruses that can infect the lining of your eyes, airways and lungs, intestines, urinary tract, and nervous system. They are common causes of fever, coughs, sore throats, diarrhea, and pink eye.
  • Retroviruses: Retrovirsuses have genes that are encoded in RNA instead of DNA. They are widely used and well-known in laboratory biology. Because they enable persistent gene expression they might be a good approach for several monogenic diseases. Immunogenicity and insertional mutagenesis are obstacles to a wider clinical use of these vectors.
  • Herpes simplex virus can be used to create vectors that can carry a large amount of genetic material, for example, for delivery to neural cells.

Gene Modified Cell Therapy

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:

  • Chimeric antigen receptor (CAR T-cell) therapies: This a way of modifying the patient’s immune cells (T cells) to recognize structures (antigens) on the surface of cancer cells. Once the T-cell receptor binds to a tumor antigen, the T cell is stimulated to attack the cancer cell.
  • T-cell receptor (TCR) therapies: T cell Receptors (TCRs) can recognize tumor-specific proteins on the inside of cells.
  • Tumor infiltrating lymphocytes (TILs): TILs infiltrate solid tumors. The therapy removes T cells from a patient and treats them to the T-cells are primed to recognize tumors. The TILs are reintroduced into the patient, generally after the patient has a low white blood cell count due to treatment with chemotherapy. TILs have been demonstrated to be effective in some forms of cancer.
  • Natural killer (NK) cell therapies: NK cells in the body can naturally recognize mutated or infected cells and eliminate them. NK cells can escape some immune attacks that might prevent them from being effective against diseased cells. They release signaling proteins that recruit and activate the body’s immune system.  NK cells derived from stem cells are being tested at present.
  • Marrow derived lymphocytes (MILs): MILS are bone marrow-derived cells that house a reservoir of T-cells. The T-cells  can be prepared to fight disease.
  • Dendritic cell vaccine: Dendritic cell vaccines, made from dendritic cells, promotes antitumor immune responses. Dendritic cells are rare cells found in the circulation system and in tissues. These specialized immune cells play a critical role in promoting an immune response, including an ability to regulate and control T-cell responses.

How to Learn More:

Gene Therapy: Your Questions Answered – This video is presented by NORD’s RareEDU™ to address a vital topic to today’s rare disease community.

Gene Editing

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. 

This illustration is meant to give the message that CRISPR-Cas9 is a gene editing tool for certain purposes, just like a socket wrench performs a specific function.

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:

  • Nucleases such as Cas9 and Cas 12a that derive from Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR/Cas)
  • Meganucleases
  • Zinc finger nucleases (ZFNs)
  • Transcription activator-like effector-based nucleases (TALEN)

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.

Gene Silencing

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. 

  • To make RNAi into medicine, developers need to deliver delicate molecules of RNA safely to their target organs. They need to shield the RNA from degradation in the bloodstream, prevent it from being filtered out by the kidneys, and let it exit blood vessels and spread through tissues.
  • Antisense oligonucleotides (ASOs), are short, synthetic DNA fragments that bind RNA through base pairing and modulate its function to silence the effect of the gene.

Tissue Engineering

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.

How to Learn More

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” 

Sangeeta Bhatia Part 1: Engineering Tissue Replacements

Regenerative Medicine

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.

Approved Cell and Gene Therapies

Several cell and gene medicines have been approved in the United States and in Europe.







Heart Abnormality

Tissue Engineered Medical Product Bio-scaffold material

Intracardiac Patch



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)

axicabtagene ciloleucel


Kite Pharma, Incorporated

USA, Europe, Canada

Retinal dystrophy

Gene therapy (Adeno-associated virus vector-based gene therapy)

voretigene neparvovecrzyl


Spark Therapeutics, Inc.

USA, Europe

Cartilage defects in the knee

Tissue engineered medical product — Autologous cellularized scaffold product

Autologous Cultured Chondrocytes on a Porcine Collagen Membrane


Vericel Corporation


Severe burns

Tissue Engineered medical product — autologous keratinocytes

Cultured Epidermal Autografts




Cancer – Prostate cancer

Autologous cellular immunotherapy

Autologous Cellular Immunotherapy


Dendreon Corp


Cancer – melanoma

Gene therapy directed at the tumor itself

Talimogene laherparepvec





Spinal Muscular Atrophy






Oral soft tissue

Tissue engineered medical product – Allogeneic cellular sheet with other factors





Spinal Muscular Atrophy






Facial Wrinkles

Autologous cellular product



Fibrocell Technologies, Inc.


Diabetic Foot ulcers

tissue engineered medical product — Bilayer dermal regeneration matrix

bilayer matrix for dermal regeneration




Making Informed Decisions

Patient-oriented organizations:

Global Genes

ELF, the Every Life Foundation

Genetic Alliance

NORD, the National Organization for Rare Disorders

The Alliance for Cancer Gene Therapy


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:

Alliance for Regenerative Medicine