AAV-mini-GDE

AAV-mini-GDE is an experimental gene therapy construct designed for the treatment of Glycogen Storage Disease Type III (GSD III), also known as Cori or Forbes disease. GSD III is an autosomal recessive metabolic disorder caused by a deficiency in the glycogen debranching enzyme (GDE), which is encoded by the AGL gene. This deficiency leads to the accumulation of limit dextrin (abnormally structured glycogen) in the liver and muscles, resulting in hepatomegaly, growth retardation, and progressive muscle weakness. The full-length human AGL cDNA is approximately 4.5 kb, which, when combined with standard promoters and regulatory elements, exceeds the optimal packaging capacity of adeno-associated virus (AAV) vectors (roughly 4.7 kb). To address this, researchers engineered a 'mini-GDE' by removing non-essential domains while preserving the enzyme's dual catalytic functions: 4-alpha-glucanotransferase and amylo-1,6-glucosidase. Delivered via an AAV vector (typically AAV8 or AAV9), AAV-mini-GDE aims to restore enzymatic activity in target tissues, facilitate the breakdown of accumulated glycogen, and alleviate the clinical manifestations of the disease.

Other names

AAV-mini-hGDEmini-GDE gene therapyAAV-truncated-GDE