The NADPH oxidase system is an enzymatic complex that generates superoxide. It is formed by membrane components, gp91-phox and p22-phox subunits (flavocytochrome b558), and cytoplasmic components (p47-phox, p67-phox and p40-phox). Defects in the expression of these components lead to Chronic Granulomatous Disease (CGD), a severe primary immunodeficiency characterized by the early onset of severe and recurrent infections. To date, allogeneic transplantation of hematopoietic stem cells has been the treatment of choice for patients affected by this disease, however, it is only available to a third of the patients due to HLA (human leukocyte antigen) compatibility issues. Gene therapy can fill this treatment gap once primary patient cells can be genetically corrected and transplanted back to the same donor, with the possibility of cure. Gene therapy protocols for CGD based on gamma-retroviral vectors have not shown good results. In this context, pre-clinical trials have shown effectiveness in correcting the expression of NADPH oxidase components by the substitution of gamma-retroviral vectors by lentiviral vectors. Considering the importance of developing an effective gene therapy for patients with CGD and the promising results found in the literature through the use of lentiviral vectors, this postdoctoral project aims the development of an efficient lentiviral vector for correcting the expression of the NADPH oxidase p47-phox component based on the chimeric vector pCCLchim, well characterized by Santilli and colleagues (2011).
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