Young boy in electric wheel chair featuring a headrest looks off camera with alert expression

How gene therapy works

Gene Replacement Therapy

Watch the video

Gene therapy has the potential to restore function in cells by delivering genetic material to specific cells containing genetic variants. Rather than treating chronic symptoms with medications over a lifetime, these therapies aim to treat the underlying genetic cause of the disorder, with one or a few treatments over time.

What are the different types of gene therapy?

Many different approaches are used in gene
therapy, depending on the condition. Gene therapy can:

  • Replace a gene that causes a disease or disorder with a gene that doesn't
  • Add genes to help the body fight or treat disease
  • Turn off genes that cause diseases
  • Be used to modify cells inside or outside the body

Types of gene therapy

The definition of what constitutes a gene therapy has been evolving over the past 20 years. At this stage, there is broad consensus that there are 2 main types of gene therapy.

An illustration of a gene inside a vector to depict gene replacement therapy

Introduce a new gene:

A functional gene is added directly into the target cell to replace the gene variant.

The added gene can:

  • Instruct the cell to produce a needed protein
  • Help another gene produce a required protein
  • Prevent a gene from producing a dysfunctional protein

The functional gene can be inserted into a vector ("delivery vehicle") to carry DNA into the cell nucleus, but the newly inserted DNA does not change the foundational structure of genes.

Examples of therapy available
Adeno-associated virus vector delivery, gene replacement therapy

An illustration of scissors to depict gene editoring or CRISPR Cas-9

Edit a gene directly:

These technologies act like scissors, cutting the DNA at a specific spot. Then scientists can remove, add, or replace the DNA where it was cut.

Example of therapy available
CRISPR-Cas9 (clustered regularly interspersed short palindromic repeats and CRISPR-associated protein 9)

How is gene therapy delivered?

Primary ways to deliver gene therapy

Illustration of petri dish and IV infusion bag depicting ex vivo gene therapy delivery

Outside of the body (ex vivo)

A sample of the patient's cells can be removed and exposed to the vector in a laboratory setting. The cells containing the vector are then returned to the patient.

IV infusion bag illustration depicting in vivo gene therapy delivery

Within the body (in vivo)

The vector can be given intravenously (by IV) or injected directly into a specific tissue in the body, where it is taken up by individual cells.

If the treatment is successful, the new gene delivered by the vector will make a functioning protein, or the editing molecules will correct a DNA error and restore protein function.

How does ex vivo gene therapy work in the body?

Ex vivo gene therapy involves the genetic modification of cells outside of the patient's body.

One example of ex vivo therapy is CAR T cell therapy (or chimeric antigen receptor T cell therapy); it introduces a gene to a person's T cells, a type of immune cell. This gene provides instructions for making a protein that attaches to specific cells. The modified immune T cells can then recognize and attack disease-causing cells.

How does in vivo gene therapy work in the body?

When in vivo gene therapy is used to introduce a new gene, it is packaged in a carrier (also called a vector) to reach a specific cell. Viruses are commonly used as vectors because they can be engineered to target specific cell types; but they are first modified so they can't cause disease in people.

Viral vectors can add and edit genes or modulate their expression. One type of viral vector that is widely used is adeno-associated viruses (AAVs), which are natural viruses that are different from adenoviruses. AAVs are smaller and less likely to cause an immune reaction than adenoviruses.

AAV vector delivery into the body

3 steps of adeno-associated virus (AAV) therapy shown in illustration. 1) Functional gene is inserted into vector. 2) Vector travels to target location in the body. 3) Vector enters target cell and releases gene therapy. 3 steps of adeno-associated virus (AAV) therapy shown in illustration. 1) Functional gene is inserted into vector. 2) Vector travels to target location in the body. 3) Vector enters target cell and releases gene therapy.

Why AAVs are widely used

  • AAVs are modified so that they do not introduce any disease-causing material; they only serve as a vector for the delivery of the gene therapy
  • AAVs can be engineered to target specific cells or tissues in the body
  • Unlike adenoviruses (AV), AAVs are not known to cause illness or disease in humans
  • AAVs can gain access to the nucleus of target cells, which is critical for them to work properly
  • Once in the nucleus, AAVs show a low risk of inserting themselves into the cell’s DNA; instead, they remain separate

Is gene therapy safe?

Scientists have been studying gene therapies since the 1970s, and clinical trials in patients have been conducted since the 1990s. As research progresses, genetic therapies hold promise to treat many diseases, but they are still a new approach and may carry risks. Potential risks could include certain types of cancer, allergic reactions, or damage to organs. Government regulatory bodies do a thorough assessment of the benefits and risks of a gene therapy when they review a treatment for approval.

Advances continue to improve gene therapy treatments and allow for a growing number of therapies to be approved for use in the US.

History of gene therapy

Before a gene therapy can be approved for use, it must be tested to assess whether the benefits of the therapy justify any risks.

Comprehensive federal regulations and guidelines—by the US Food and Drug Administration (FDA) and National Institutes of Health (NIH)—protect people participating in clinical trials. The FDA can reject or suspend clinical trials that are suspected to be unsafe.

Companies developing gene therapies and other treatments must demonstrate that they meet the FDA's standards for safety and quality before they can conduct a clinical trial in human patients.

Gene therapy timeline. 50 years of advancements in treating genetic disease from 1972 to 2022. Gene therapy timeline. 50 years of advancements in treating genetic disease from 1972 to 2022.
  • 1972

    First time gene therapy proposed as treatment for genetic disorders

  • 1989

    First human test demonstrated safety of retroviral vector for gene therapy

  • 1990

    First patient successfully treated with gene therapy for severe combined immunodeficiency

  • 1995

    First human AAVs used in cystic fibrosis

  • 1999

    In a clinical trial, a patient developed the first fatal response to an experimental gene therapy treatment for ornithine transcarbamylase deficiency

  • 2003

    China approved world’s first commercial gene therapy for head and neck squamous cell carcinoma

  • 2012

    First European Medicines Agency (EMA) approval of recombinant AAV1-LPL to treat lipoprotein lipase deficiency

  • 2017

    FDA approval of first CAR T cell therapy to treat a form of acute lymphoblastic leukemia

  • 2017/2018

    FDA/European Union (EU) approvals of AAV2-RPE65 to treat inherited retinal dystrophy

  • 2019

    FDA approval of AAV9-SMN1 for spinal muscular atrophy (SMA)

  • 2020

    EU approval of AAV9-SMN1 for SMA

  • 2022

    FDA approval of an AAV therapy for hemophilia and a lentiviral gene therapy for β-thalassemia

How is gene therapy made?

Gene therapy manufacturing is a multistep process requiring advanced technology and facilities to produce high-quality gene therapeutics.

Gene therapy manufacturing is a much more complex process than that of traditional medicines, such as small-molecule compounds that are derived from chemicals.

Developing clinical-grade viral vectors for use in gene therapy requires a cell-based, large-scale manufacturing system that supports living cells so that the functional gene can be inserted into a viral vector.

Calendar of one month icon

A process that may take months

Strict controls to keep sterile conditions

Test tube containing a liquid icon

Ensuring quality

Safety & efficacy

Pill bottle with plus sign on front


Cells need to be maintained in controlled conditions

Icon of hand holding a test tube containing a liquid

Securing the necessary amount

A single gene therapy treatment may require hundreds of thousands or millions of cells depending on the target in the body

Significant progress has been made in manufacturing safe, efficient, and economical delivery systems for therapeutic genetic material and viral vectors. Researchers continue to develop novel approaches to improve the capacity and capabilities of the technology.

Learn more