Krabbe disease is a lysosomal storage disorder caused by GALC (galactocerebrosidase) mutation. According to the onset time and severity, it can be divided into the infantile type, juveniletype and adult type. Patients showed progressive demyelination, severe gliosis, the presence of globoid cells, and destruction of brain cells. Hematopoietic stem cell transplantation has been proved to relieve the development of the symptoms and benefit the patients. To further improve the therapeutic approach for Krabbe disease and other lysosomal storage disorders, our lab is developing new strategy by using lentivirus mediated gene therapy with hematopoietic stem cells (HSC). Galc gene under myeloid specific promoter was introduced into HSC by lentiviral vector. After transplantation, myeloids differentiated by engineered HSC will overexpress and secrete functional Galc protein constantly to benefit the patient. While in HSC, Galc construct will maintain silent to maintain normal HSC function.
Generating an inducible non-integrated lentiviral packaging cell line. The availability of a lentivirus packaging cell line would facilitate the stable production of high-titer lentivirus vectors for gene therapy.