@article{Hu2025, 
author = {Mingfeng Hu and Qiling Xu and Fang Zhang and Karen F. Buckland and Yelei Gao and Weixia Du and Yuan Ding and Lina Zhou and Xiulian Sun and Lijia Ma and Zhiyong Zhang and Xuemei Tang and Xiaodong Zhao and Adrian J. Thrasher and Yunfei An},
title = {Preclinical ex vivo IL2RG gene therapy using autologous hematopoietic stem cells as an effective and safe treatment for X-linked severe combined immunodeficiency disease},
year = {2025},
journal = {Genes & Diseases},
volume = {12},
number = {3},
pages = {101445},
keywords = {Atypicaldiverse phenotype, Gene therapy, IL2RG, Self-inactivating lentiviral vector, X-linked severe combined immunodeficiency disease},
url = {https://www.sciopen.com/article/10.1016/j.gendis.2024.101445},
doi = {10.1016/j.gendis.2024.101445},
abstract = {X-linked severe combined immunodeficiency disease (X-SCID) is a rare inherited disease caused by mutations in the interleukin 2 receptor subunit gamma gene (IL2RG), which encodes the common γ chain protein, a subunit of the receptor for lymphocytes. X-SCID is characterized by profound defects in T-cell, B-cell, and natural killer cell function. Here, we report a Chinese cohort of nine X-SCID patients with six novel IL2RG mutations. Among those, the two adolescent patients with an atypical immunotype were confirmed by further analyzing IL-2-JAK-STAT5 signaling, T cell proliferation, and T cell receptor excision circles (Trecs). Interestingly, Bacillus Calmette-Guérin (BCG) disease occurred commonly in this cohort. Although allogeneic hematopoietic stem-cell transplantation is curative for the disease, it is not available to all patients due to the lack of suitable matched donors. Autologous gene therapy using a self-inactivating lentiviral vector (SIN-LV) technology has provided an alternative therapy for such mono-genetic diseases. Here, we performed the pre-clinical studies to assess our SIN-LV carrying IL2RG on human ED7R cells deficient in IL2RG and CD34+ stem cells derived from the bone marrow of a healthy donor and a patient with X-SCID. This work is done complied with the established “Good Manufacturing Practice” (GMP) used in the clinical trials. In addition, a safety study is performed using the transduced CD34+ cells implanted into the axilla of nude mice in vivo. Overall, our studies have demonstrated the efficiency and safety of SIN-IL2RG-LV, which paves the way for conducting X-SCID gene therapy clinical trials in China in the near future.}
}