Understanding how ADAR1 mutations cause Aicardi-Goutières’s Syndrome

Mutations in ADAR1 are one cause of Aicardi-Goutières’s Syndrome (AGS). AGS is a rare inherited disease that affects the brain and is a form of type I interferonopathy. Currently there are no effective treatments for AGS. Editing by ADAR1 is essential that cells can tell the difference between RNAs that are made by the cell and so not a threat compared to nucleic acids derived from pathogens such as viruses that invade the cell. We will use models of the most common human ADAR1 mutations reported in AGS to understand how these cause disease and to try to develop targeted interventions that can prevent disease progression. We will use genetics, in vivo models and transcriptomics to understand how mutant ADAR1 causes disease.