Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 18 2 2019 04 01 131 142 EN Arefeh Jafarian Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran Gelareh Shokri Stem Cell Technology Research Center, Tehran, Iran Mahdieh Shokrollahi Barough Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran AND Department of Cancer Immunotherapy and Regenerative Medicine, Breast Cancer Research Center, Motamed Cancer Institute, Academic Center for Education, Culture and Research (ACECR), Tehran, Iran Mostafa Moin Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran Zahra Pourpak Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran Masoud Soleimani Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran 2018 02 12 2018 07 15 The Chronic granulomatous disease (CGD) is a primary immunodeficiency that characterized by mutations in phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, resulting in deficient antimicrobial activity of phagocytic cells and recurrent childhood infections. Hematopoietic stem cell transplantation (HSCT) is a curative option for patients with human leukocyte antigen (HLA) matched donor, when conventional cares and therapies fail. However, in many cases when the patients have not an HLA-matched donor, they need to a method to recapitulate the function of the affected gene within the patient’s own cells. Gene therapy is a promising approach for CGD. While, the success of retroviral or lentiviral vectors in gene therapy for CGD has been hampered by random integration and insertional activation of proto-oncogenes. These serious adverse events led to improvement and generations of viral vectors with increased safety characteristics. Gene therapy continues to progress and the advent of new technologies, such as engineered endonucleases that have shown a great promise for the treatment of genetic disease. This review focuses on the application of gene therapy for the CGD, the limitations encountered in current clinical trials, advantages and disadvantages of endonucleases in gene correction and modeling with CRISPR/Cas9 approach.  https://ijaai.tums.ac.ir/index.php/ijaai/article/view/1868 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/1868/1392