Lentiviral vectors are the currently being used for gene therapy for several monogenetic diseases. We are developing novel lentiviral vectors for gene therapy for haemoglobinopathies. In collaboration with Dr. Trent Spencer, Emory University we developed two novel gene addition vectors, CSCREU1 and CSCREU2 to express beta globin and gamma globin genes. We have tested these two vectors in a sickle cell mouse model and were found to have significant expression of the transgenes resulting in phenotype correction. Additionally, we are in the process of developing a vector to express an shRNA for knocking down the expression of BCL11A for gene therapy for haemoglobinopathies. The initial studies performed in an ex-vivo erythropoiesis model showed that this vector can activate gamma globin gene significantly in the cultured erythroid cells. We are currently evaluating these vectors by transducing HSCs from patients with haemoglobinopathies with the generated lentiviruses and transplanting them in NSG/NSGW mice.
Figure: Current approaches to gene theraphy for haemoglobin disorders