An engineered β-glucocerebrosidase with improved stability and cross-correction for the potential treatment of Gaucher disease
Gaucher disease (GD) is caused by the lysosomal accumulation of glucosylceramide and glucosylsphingosine due to mutations in GBA1, the gene for β-glucocerebrosidase (GCase). While enzyme replacement therapies exist for treatment of Type 1 Gaucher patients there is a clear unmet need in neuronopathic GD2 and 3, as well as opportunities for improved outcomes for GD1 patients.
Using the CodeEvolver® directed evolution platform, more stable and efficacious GCase transgenes have been developed as potential next generation gene therapy treatments. In this poster we characterize the AAV capsid containing an engineered GBA1 (GCase). The improvements in the intrinsic stability, activity and expression of the engineered GCase demonstrate enhanced efficacy in the Gaucher disease mouse model when compared to wild-type GCase when delivered as an AAV gene therapy.