The goal of gene therapy is to introduce DNA instructions or transgenes to cells in the body to treat a disease. While there are many types of transgenes that can be used, one common feature is that transgenes require a vector for transportation into different tissues and cells throughout the body. One such vector is Adeno-associated virus or AAV, which has many properties that make it well suited for use in gene therapy. AAV is a naturally occurring virus, not known to cause disease in humans, that has the ability to reach many tissues in the body.
There are multiple types of AAV, which are referred to as serotypes. You may be familiar with some of these, such as AAV8, AAV9, or AAVrh74. Each one of these serotypes has a different tropism, which means they have an affinity for targeting certain tissues in the body, though the AAV will transport the transgene into other tissues as well. Duchenne gene therapies use serotypes that target muscle and heart tissues. Researchers are also developing new versions of AAVs that aren’t found in nature, but may have properties that allow for better delivery of the transgene to cells in the body.
AAV is a small virus so the amount of DNA that can be packaged inside it is limited. This means there is a restriction on the size of transgene that AAV can carry and transport into cells. Researchers have to try to optimize the genetic information in a transgene, such as creating a much smaller micro-dystrophin transgene rather than packaging the entire dystrophin gene.
Gene therapy is a therapeutic strategy to treat disease at the genetic level in an individual as opposed to traditional medicines that deliver compounds into the body to induce change.
This is done through a number of approaches, including:
You may hear terms like gene addition, gene replacement, or gene editing, all of which refer to the overall strategy of gene therapy.
In these instances genetic material, referred to as the transgene, is delivered to cells for a specific purpose. Transgenes are carried into cells using vectors. In the case of current Duchenne gene therapy programs, a virus called Adeno-associated virus (AAV) is used to deliver the transgene into the cells.
AAV is a small virus, so this does place a limit on how large of a transgene can be used for gene therapy currently.
There are strategies being explored to use multiple viruses or using non-viral vectors, but those strategies are not yet in clinical trials or available to people with Duchenne.
