New to MyHealth?
Manage Your Care From Anywhere.
Access your health information from any device with MyHealth. You can message your clinic, view lab results, schedule an appointment, and pay your bill.
ALREADY HAVE AN ACCESS CODE?
DON'T HAVE AN ACCESS CODE?
NEED MORE DETAILS?
MyHealth for Mobile
Correction of beta-thalassemia major by gene transfer in haematopoietic progenitors of pediatric patients
Correction of beta-thalassemia major by gene transfer in haematopoietic progenitors of pediatric patients EMBO MOLECULAR MEDICINE Roselli, E. A., Mezzadra, R., Frittoli, M. C., Maruggi, G., Biral, E., Mavilio, F., Mastropietro, F., Amato, A., Tonon, G., Refaldi, C., Cappellini, M. D., Andreani, M., Lucarelli, G., Roncarolo, M. G., Marktel, S., Ferrari, G. 2010; 2 (8): 315-328Abstract
Beta-thalassemia is a common monogenic disorder due to mutations in the beta-globin gene and gene therapy, based on autologous transplantation of genetically corrected haematopoietic stem cells (HSCs), holds the promise to treat patients lacking a compatible bone marrow (BM) donor. We recently showed correction of murine beta-thalassemia by gene transfer in HSCs with the GLOBE lentiviral vector (LV), expressing a transcriptionally regulated human beta-globin gene. Here, we report successful correction of thalassemia major in human cells, by studying a large cohort of pediatric patients of diverse ethnic origin, carriers of different mutations and all candidates to BM transplantation. Extensive characterization of BM-derived CD34(+) cells before and following gene transfer shows the achievement of high frequency of transduction, restoration of haemoglobin A synthesis, rescue from apoptosis and correction of ineffective erythropoiesis. The procedure does not significantly affect the differentiating potential and the relative proportion of haematopoietic progenitors. Analysis of vector integrations shows preferential targeting of transcriptionally active regions, without bias for cancer-related genes. Overall, these results provide a solid rationale for a future clinical translation.
View details for DOI 10.1002/emmm.201000083
View details for Web of Science ID 000281520500005
View details for PubMedID 20665635