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How is gene therapy designed to work?

It’s not magic – it’s science in progress

Many gene therapies are under investigation and some have been approved for use for conditions other than haemophilia A or B. The risks and benefits of each gene therapy are evaluated independently and if a clinical trial for a particular gene therapy is successful, it has the potential to offer a remarkably different approach to the way we’ve historically managed genetic disease. Let’s look at an example:


Currently undergoing clinical trials in many different conditions, including haemophilia A and B, this method of gene therapy aims to introduce a functioning gene that can instruct the body to produce the needed protein.


The gene transfer process begins when a functional copy of a mutated gene is created in a laboratory. The functional gene is developed to contain the instructions for making a needed protein.


The functional gene now has to be delivered into the body. To protect the gene and allow it to be introduced into the body, a transport vehicle is created from a viral shell.

This viral shell is created with no viral genes inside. The combination of a functional gene within the transport vehicle is called a therapeutic vector.

Viruses used in gene transfer include adenovirus, adeno-associated viruses (AAV) and lentiviruses. For some AAV-based gene therapies, prospective patients may need to take a simple blood test to determine eligibility. The test will screen for the presence of AAV antibodies, which have the potential to reduce treatment efficacy.

Ongoing studies are also evaluating the body’s immune response to gene therapy.


The therapeutic vector is designed to target the functional gene toward a preferred tissue. In haemophilia A and B, the liver is the target because it can make the proteins required for blood to clot. In other diseases, such as Huntington disease, the brain is the target.

When the functional gene is placed inside the AAV, additional DNA is included that is intended to allow it to work and promote production of the protein only within the targeted cells. Research is ongoing to understand to what extent the AAV may deliver the functional gene to the body’s other tissue

Making Proteins

Once introduced in the body, the new gene is designed to work in place of the gene that isn’t functioning properly. If successful, the goal for this new gene is to provide instructions for the body to make the protein it needs. In the case of haemophilia, the liver is targeted to make the proteins.

The new, functional gene enters the nucleus of the targeted cells. There, it is generally expected to reside as an episome, or circular piece of DNA, outside the chromosomes. Gene transfer is not designed to replace or edit the existing gene. Therefore, the mutated gene could still be passed on to future generations. In some cases, the gene integrates directly into the existing DNA. Research is ongoing to better understand the rate and impact of this integration.


To optimise response to gene therapy and evaluate safety, it may be important to monitor the prospective patient after treatment with gene therapy.

Ongoing clinical trials are being conducted to understand how gene therapy will affect the human body. Please be sure to read through the section “WHAT ARE THE POSSIBLE RISKS OF GENE THERAPY?”