Lentiviral gene therapy for X-linked chronic granulomatous disease

UMMS Affiliation

Department of Pediatrics

Publication Date


Document Type



Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Hematology | Hemic and Lymphatic Diseases | Pediatrics


Chronic granulomatous disease (CGD) is a rare inherited disorder of phagocytic cells(1,2). 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 12 months. 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 3 months of treatment from pre-existing comorbidities. At 12 months, 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 12 months follow-up, suggesting that autologous gene therapy is a promising approach for CGD patients.

DOI of Published Version



Nat Med. 2020 Feb;26(2):200-206. doi: 10.1038/s41591-019-0735-5. Epub 2020 Jan27. Link to article on publisher's site

Journal/Book/Conference Title

Nature medicine


Full list of authors omitted for brevity. For full list see article.

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