AAV9-SBF1 split-intein gene therapy

AAV9-SBF1 split-intein gene therapy is a preclinical dual-vector adeno-associated virus serotype 9 gene-replacement approach for Charcot-Marie-Tooth disease type 4B3. It delivers complementary 5-prime and 3-prime portions of the large SBF1 coding sequence, each fused to a split intein, because the full SBF1 coding sequence exceeds the payload capacity of a single AAV vector. Following co-transduction, split-intein-mediated protein trans-splicing reconstitutes full-length SBF1 protein in target tissues. In reported neonatal mouse studies, Npu split-intein vector pairs produced the strongest reconstitution, with SBF1 expression detected in peripheral nerves, spinal cord, and skeletal muscle after systemic AAV9 administration. This program is being developed as a potential disease-modifying treatment for CMT4B3 and remains preclinical.