About in vivo Genome Editing
Gene therapy is a treatment approach that attempts to treat a genetic problem at its source. When a mutated gene occurs in your body, it can affect how your cells create proteins and how those proteins behave, leading to disease. Gene therapy attempts to add a working copy of a defective gene to the patient’s cells, helping the cells function normally. This is different from a traditional drug-based approach, which may treat symptoms but not the actual genetic problems.
Since genes can’t be delivered into cells on their own, they need to have a helper, called a vector. Viruses are often used as vectors because they can easily penetrate the cell. Once inside, the information in the gene is used by the cell to build RNA and proteins. The proteins can then carry out their job in the cells. SB-FIX, the investigational drug in this study, is a type of gene therapy known as in vivo genome editing.
For hemophilia B, the goal is to deliver a normal gene into liver cells so they can produce the right amount of the clotting Factor IX (FIX) for adequate clotting. SB-FIX (the investigational therapy) consists of three vectors, each carrying a different payload. Two of these vectors carry genes for proteins that work like targeted genetic scissors to cut at a specific genomic site in your liver cells. The third vector, carrying the therapeutic Factor IX gene, can then be inserted into the endogenous DNA in your liver cells. This process is known as in vivo genome editing.
The vectors to be used in this study are adeno-associated viruses (AAV) that have been modified so they can carry genes that are potentially therapeutic. AAV is used to penetrate into liver cells but does not cause any known disease. This AAV has been changed in the laboratory so it can no longer grow or reproduce in the human body.
AAV is introduced following a single infusion of SB-FIX into a vein in your arm. SB-FIX uses zinc finger nucleases (ZFNs) to place a therapeutic Factor 9 gene into the genome of liver cells to drive constitutive expression of therapeutic Factor IX protein. See the tab “A Little More Science” for details.
Because the Factor 9 gene is permanently inserted into the patient’s liver cells via genome editing, SB-FIX may provide lifelong expression and therapeutic benefit for hemophilia B subjects. This is something that will be evaluated in this study.
Right now the FIXtendz study is testing SB-FIX for severe hemophilia B. See if you qualify, to be referred to a doctor participating in the study.