AAV-FTO-3KR

AAV-FTO-3KR is an investigational gene therapy constructed by packaging a mutant form of the fat mass and obesity-associated (FTO) gene (specifically, the FTO-K216/357/365R mutant, abbreviated as 3KR) into an adeno-associated virus (AAV) vector. The therapy is being evaluated for its effects on bone loss associated with inflammatory bowel disease (IBD). Mechanistically, AAV-FTO-3KR modulates the SUMOylation status of FTO in bone marrow mesenchymal stromal cells (BMSCs), thereby restoring osteogenic differentiation and mitigating IBD-induced bone loss. Preclinical studies in IBD mouse models demonstrated that AAV-FTO-3KR, alone or in combination with the IL-6R monoclonal antibody tocilizumab, promotes bone formation and blocks the adipogenic shift of BMSCs. This candidate represents a gene therapy approach targeting m^6A epitranscriptomic modifications through modulation of FTO SUMOylation.