Signal Peptide Engineering and Codon Optimization to Enhance α-Gal A Activity for rAAV Gene Therapy of Fabry Disease - PubMed
12 hours ago
- #Fabry disease
- #gene therapy
- #signal peptide
- Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the GLA gene, leading to deficient α-Gal A activity.
- Signal peptide engineering identified sp21, which increased α-Gal A enzyme activity by 2.3 times in conditioned media.
- Codon optimization of the human GLA gene (hGLAco) resulted in a 4-fold increase in secreted α-Gal A activity in vitro.
- rAAV8 vectors with hGLAco and sp21 driven by a liver-specific promoter showed a 6.9-fold increase in α-Gal A activity in Fabry mice.
- The engineered GLA gene effectively cleared toxic Lyso-Gb3 accumulation in plasma and key tissues.