Provided by and printed with permission by BioMarin

It鈥檚 not magic鈥攊t鈥檚 science in progress. Many gene therapies are under investigation and some have been approved for use for conditions other than hemophilia 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鈥檝e historically managed genetic diseases. No gene therapies for hemophilia A or B have been approved for use or determined to be safe or effective. Let鈥檚 look at an example of how the research is being conducted:


Currently undergoing clinical trials in many different conditions, including hemophilia A and B, this method of gene therapy aims
to introduce a working, or functional, gene into the body intended to produce a needed protein.

Creating a Working Gene

The gene transfer therapy begins when a working gene is created in a laboratory. The working gene is developed to contain the instructions for making a needed protein.

Scientists design working genes to meet a disease鈥檚 specific needs. For example, in patients with hemophilia A, an F8 gene is needed to code for factor VIII protein, which is essential for clotting, and in hemophilia B, an F9 gene is needed to code for factor IX protein.

Building a Therapeutic Vector

The working gene now has to be delivered into the body. To do so, a therapeutic vector is created. This therapeutic vector is created by modifying a naturally-occurring virus; the shell of the virus is created without the viral DNA, and the working gene is put inside the empty shell. No longer a virus, the therapeutic vector is designed to deliver the working gene to the cells in the body where it is needed.

Determining Eligibility

As part of gene therapy research, a healthcare provider must determine whether a patient is eligible.
Factors such as age, gender and liver health may be considered. Therapeutic vectors being used in research
are commonly made from adeno-associated viruses (AAVs). These viruses are not known to make people sick. They are found naturally around the world, so some people will have already developed immunity to them via exposure at some point in the past. Having preexisting immunity to the AAV used by a gene therapy could reduce or eliminate its effectiveness. Because of this, candidates may have to be screened with a blood test to ensure that they do not have immunity.

Delivering the Working Gene

Once the patient is determined to be eligible, the
gene therapy is ready for administration to evaluate its safety and effectiveness. A single, one-time infusion in an appropriate clinical infusion setting delivers large numbers of therapeutic vectors into the body. The therapeutic vector is designed to both protect and guide the working

Research is ongoing to determine the possible impact of the therapeutic vector delivering the working gene to the other cells in the body. Once in the body, the new gene is designed to do the work of the gene that is missing or isn鈥檛 functioning properly. The goal is to provide instructions for the body to make the protein it needs on its own, and ongoing research is evaluating the risks and impact of introducing the new gene.

Because the new, working gene is not intended to become part of your DNA, the original missing or mutated gene is left unchanged. Gene transfer is not designed to replace or edit the existing gene, which means that the mutated gene could still be passed to future generations.

Monitoring Safety and Efficacy

Regular monitoring after gene therapy is important because it allows researchers to understand any risks and what impact the gene transfer is having. Patients in clinical trials meet with their care team for blood tests, and to discuss their medication regimen and lifestyle to collect data as part of the study. As with all medications, response to gene therapy may vary. How long gene therapy might keep working is being evaluated in ongoing clinical trials with researchers aiming to create a long-lasting therapy.

As of publication, no gene therapies for hemophilia A or B have been approved for use or determined to be safe or effective.

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