AAV8 SaCas9 vector with Hadhb repair template

AAV8 SaCas9 vector with Hadhb repair template is an experimental CRISPR-based gene therapy designed to treat mitochondrial trifunctional protein deficiency (TFP-D). The therapy utilizes an adeno-associated virus serotype 8 (AAV8) vector to deliver the Staphylococcus aureus Cas9 (SaCas9) nuclease along with a 400 bp wild-type Hadhb repair template. This system is engineered to correct the pathogenic p.M404K variant in the Hadhb gene through homology-directed repair (HDR). By converting the mutant allele to the wild-type sequence, the therapy aims to restore the stability and function of the mitochondrial trifunctional protein complex, which is essential for long-chain fatty acid beta-oxidation. Preclinical data in mouse models have demonstrated that this genome editing approach can significantly improve metabolic markers and reduce elevated long-chain acylcarnitines, addressing the dominant-negative effect of the Hadhb mutation.