AAV9-Split-ABE

AAV9-Split-ABE is an experimental gene therapy candidate being investigated for the treatment of infantile-onset Pompe disease (IOPD). The therapy employs an adenine base editor (ABE) to correct pathogenic transition mutations in the *GAA* gene, which encodes the lysosomal enzyme acid α-glucosidase. Due to the large size of the ABE cassette, which exceeds the packaging capacity of a single adeno-associated virus (AAV) vector, the system uses a split-intein approach. This involves dividing the ABE into N-terminal and C-terminal halves, each packaged into a separate AAV9 vector. Upon co-transduction of target tissues like cardiac and skeletal muscle, the halves are expressed and reconstituted into a functional editor via protein trans-splicing. The reconstituted ABE then mediates precise A-to-G base conversion to restore GAA enzyme function and reduce toxic glycogen accumulation.