• About genetic disease
  • What is gene therapy?
  • What is gene therapy meant to do?
  • What is the potential of gene therapy?
  • About genetic disease

    Understanding genetic disease

    The human body is composed of trillions of cells. Cells are the basic building blocks of all living things. The command center of each cell is called the nucleus, and it contains chromosomes. Chromosomes are made up of DNA (deoxyribonucleic acid)—the body’s hereditary material.

    Genes are segments (pieces) of DNA. They contain instructions for making proteins. Genes are inherited (passed down) from parent to child, half from the mother and half from the father.

    DNA has its own alphabet: A, C, G, T. The letters stand for the 4 nucleotides, which are the building blocks of DNA. Unique combinations of adenine (A), cytosine (C), guanine (G), and thymine (T) make up all of the genes in the body.

    Original DNA sequence

    A gene mutation is a change in the sequence of DNA that makes up a gene. There are different types of gene mutations including:

    Gene deletion mutation

    Deletion: A segment of DNA is deleted or lost

    Gene substitution mutation

    Substitution: A segment of DNA is replaced with a different segment

    Gene duplication mutation

    Duplication: A segment of DNA is repeated, resulting in multiple copies of that genetic information

    Mutations can be passed from parent to child or be acquired (occurring randomly or caused by exposure to something in the environment). Some gene mutations are harmless, but others can result in a genetic disease.

    What is gene therapy?

    Introduction to gene therapy research

    Gene therapy is a potential approach to treating or preventing genetic diseases. The goal of gene therapy is to address a genetic disease at its source—the gene. This can be done by modifying (changing) genes or creating new genes in a laboratory and delivering them to specific cells in the body.

    What is gene therapy meant to do?

    Modified virus carrying a healthy gene into a targeted cell

    Gene therapy step by step

    First, a healthy replacement gene is placed in a delivery vehicle, called a vector. This step occurs outside of the body. Then, the vector is inserted into the body and carries the healthy gene into specific target cells where it is needed.

    Viruses are commonly used as vectors because of their natural ability to enter specific cells in the body. Viruses used as vectors, or viral vectors, are modified (changed) before use in gene therapy. Once the virus is modified to be used as a vector, it is intended to transport the replacement gene to target cells without causing disease.

    The viral vector can then carry and deliver the healthy gene into targeted cells. When the healthy gene is delivered to the cell, it is released from the viral vector with the goal of replacing a mutated gene, introducing a new gene, or knocking out a mutated gene.

    If transferred successfully, the healthy gene is intended to:

    • Provide the correct instructions for the cell to make a functioning protein or stop producing a harmful protein
    • Reduce the harmful effects of a genetic disease or even make it go away altogether

    What is the potential of gene therapy?

    Genetic diseases that may be treated using a gene therapy approach

    Gene therapy has the potential to treat many diseases, including some that are caused in part or in full by gene mutations. Some of these diseases include:

    Blood-clotting diseases such as hemophilia

    Blood-clotting diseases, such as hemophilia

    Cardiovascular diseases

    Cardiovascular diseases

    Infectious diseases

    Infectious diseases

    Neurodegenerative diseases

    Neurodegenerative diseases

    Vision disorders

    Vision disorders

    Gene therapy research for hemophilia

    Gene therapy research for hemophilia seeks to replace the mutated gene that is causing a clotting factor deficiency with a new, healthy gene. The healthy gene would be delivered to liver cells, allowing the body to begin making the clotting factor.

    There are two forms of gene therapy currently being investigated for hemophilia:

    • Gene transfer with vector AAV, or adeno-associated virus, to deliver a healthy and functioning new gene
    • Genome editing to change, remove, or add new DNA to the cell’s native (original) DNA

    The pioneering research of gene therapy for hemophilia began in the late 1990s. To date, more than 20 clinical studies of gene therapy to treat hemophilia have been conducted, are underway, or are planned. Recently, results of investigational gene therapy trials for hemophilia A and B were published.

    If you’re interested in learning more about gene therapy clinical trials for hemophilia, visit ClinicalTrials.gov.