美国加州大学旧金山分校Donald B. Kohn、英国大奥蒙德街儿童医院Adrian J. Thrasher等研究人员合作利用慢病毒基因疗法治疗了X基因连锁的慢性肉芽肿性疾病。该研究于2020年1月27日在线发表于国际一流学术期刊《自然—医学》上。

Title: Lentiviral gene therapy for X-linked chronic granulomatous disease

Author: Donald B. Kohn, Claire Booth, Elizabeth M. Kang, Sung-Yun Pai, Kit L. Shaw, Giorgia Santilli, Myriam Armant, Karen F. Buckland, Uimook Choi, Suk See De Ravin, Morna J. Dorsey, Caroline Y. Kuo, Diego Leon-Rico, Christine Rivat, Natalia Izotova, Kimberly Gilmour, Katie Snell, Jinhua Xu-Bayford Dip, Jinan Darwish, Emma C. Morris, Dayna Terrazas, Leo D. Wang, Christopher A. Bauser, Tobias Paprotka, Douglas B. Kuhns, John Gregg, Hayley E. Raymond, John K. Everett, Geraldine Honnet, Luca Biasco, Peter E. Newburger, Frederic D. Bushman, Manuel Grez, H. Bobby Gaspar, David A. Williams, Harry L. Malech, Anne Galy, Adrian J. Thrasher

Issue&Volume: 2020-01-27

Abstract: Chronic granulomatous disease (CGD) is a rare inherited disorder of phagocytic cells1,2. We report the initial results of nine severely affected X-linked CGD (X-CGD) patients who received ex vivo autologous CD34+ hematopoietic stem and progenitor cell-based lentiviral gene therapy following myeloablative conditioning in first-in-human studies (trial registry nos. NCT02234934 and NCT01855685). The primary objectives were to assess the safety and evaluate the efficacy and stability of biochemical and functional reconstitution in the progeny of engrafted cells at 12months. The secondary objectives included the evaluation of augmented immunity against bacterial and fungal infection, as well as assessment of hematopoietic stem cell transduction and engraftment. Two enrolled patients died within 3months of treatment from pre-existing comorbidities. At 12months, six of the seven surviving patients demonstrated stable vector copy numbers (0.4–1.8 copies per neutrophil) and the persistence of 16–46% oxidase-positive neutrophils. There was no molecular evidence of either clonal dysregulation or transgene silencing. Surviving patients have had no new CGD-related infections, and six have been able to discontinue CGD-related antibiotic prophylaxis. The primary objective was met in six of the nine patients at 12months follow-up, suggesting that autologous gene therapy is a promising approach for CGD patients.

DOI: 10.1038/s41591-019-0735-5

Source: https://www.nature.com/articles/s41591-019-0735-5