GENE-TRANSFER THERAPY OF GAUCHER DISEASE

Gaucher disease is a hereditary disorder of glycosphingolipid metaboli sm caused by deficiency of lysosomal glucocerebrosidase (GBA) and char acterized by accumulation of glucocerebroside in macrophages of the mo nonuclear phagocyte system (MPS; also called the reticuloendothelial s ystem). Enzyme replacement treatment of the disease is highly effectiv e; however, it is extremely expensive and inconvenient. Attempts at ge netic correction by gene transfer therapy in patients with Gaucher dis ease are currently under investigation. All recently approved clinical trial protocols involve ex vivo transduction of hematopoietic stem ce lls by murine retrovirus vectors containing human GBA cDNA. We are cur rently exploring the potential efficacy of in vivo gene transfer strat egies for correction of the defect in Gaucher disease, using GBA incor porated into cationic liposomes and infused intravenously in mice.