AAV-PR-ABE

AAV-PR-ABE is an experimental gene therapy designed to treat Multisystemic Smooth Muscle Dysfunction Syndrome (MSMDS), a rare genetic disorder caused by mutations in the *ACTA2* gene, most commonly the p.R179H variant. The therapy utilizes a novel smooth muscle cell (SMC)-tropic adeno-associated virus (AAV-PR) to deliver a bespoke CRISPR-Cas9 adenine base editor (ABE) and a specific guide RNA. This system performs precise A-to-G base editing to correct the pathogenic mutation in smooth muscle cells throughout the body, including the gastrointestinal tract, vasculature, and eyes. Preclinical studies in mouse models have demonstrated that AAV-PR-ABE can restore actin organization, improve smooth muscle contractility, and rescue phenotypes such as gut dysmotility, retinal vasculopathy, and pupillary mydriasis. The therapy is typically delivered using a dual-AAV strategy due to the large size of the base editing machinery.