A plain language summary of AAV-based gene therapy: challenges and potential solutions for people with antibodies against AAV

Abstract

This is a summary of a review article about gene therapy. Review articles summarize many previously published scientific articles. The review was about how a common virus could change how one type of gene therapy works. It also discussed the importance of antibody testing for people who may receive gene therapy. The original review was published in Molecular Therapy in 2023. Gene therapy is a type of medical treatment. The goal of a specific gene therapy is to treat a specific genetic condition. A genetic condition is a health problem caused by a variation (change or mutation) in a gene or genes. Genes are instructions that tell the body how to grow and work. Some genetic conditions can cause rare diseases. A rare disease affects only a very small percentage of people. Gene therapy may help people with some rare diseases because it aims to correct the root cause of the condition instead of just treating symptoms. Gene therapies work by getting into the cells in a person's body. Many gene therapies are modeled after viruses because viruses are good at getting into the body. One of the viruses used in gene therapy is called adeno-associated virus (AAV for short). This naturally occurring virus infects many people. People can get infected without realizing it because AAV doesn't typically make a person sick. After being infected with a virus, people make antibodies to fight off that virus. These antibodies can prevent another infection. Antibodies that fight off natural AAV may prevent gene therapy based on AAV from working as it should. A common reason why people may not be able to receive gene therapy is because they have antibodies against AAV. This means that some people with some genetic conditions or rare diseases may not be able to benefit from gene therapy. Researchers are trying to understand how antibodies against AAV can prevent gene therapy from working. They are also studying what side effects they may cause. This research is important for people with a genetic condition or rare disease that may be treated with gene therapy. People who have a certain level of antibodies against AAV might not be able to take part in gene therapy clinical trials. They might not be able to receive AAV-based gene therapies that have been approved for commercial use by a regulatory agency such as the FDA (Food and Drug Administration) or EMA (European Medicines Agency). For most gene therapies, people need to be tested for antibodies against AAV. There are two different types of tests that measure if someone has antibodies against AAV. Researchers are looking at ways to lower the effects of antibodies against AAV. This research could allow more people to have gene therapy in the future.