This site is an educational service brought to you by BioMarin. No gene therapies for haemophilia A or B have been approved for use or determined to be safe or effective.

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:



Gene transfer therapy

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.



DNA is placed in the viral vector

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 neutralised virus.

The transport vehicle created from a neutralised virus is called a therapeutic vector. The neutralised virus is created by removing the inner viral material in a lab, leaving behind an empty protein shell.

Viruses used in gene transfer include adenovirusadeno-associated viruses (AAV) and lentiviruses. Ongoing studies are evaluating the body’s immune response to gene therapy.



A functional gene is placed inside the transport vehicle and large numbers are administered via an intravenous infusion. Once the transport vehicle has a functional gene inside, it is called a therapeutic vector. 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 tissues.



Proteins in the body

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. The original genetic material found in the chromosomes is intended to be left unchanged. This means the mutated gene would still be there and can be passed on to a person’s offspring. In some cases, the gene integrates directly into the existing DNA. Research is ongoing to better understand the rate and impact of this integration.

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 RISKS OF GENE THERAPY?”