Preclinical safety and efficacy of lentiviral-mediated gene therapy for leukocyte adhesion deficiency type I.

ABSTRACT: Leukocyte adhesion deficiency type I (LAD-I) is a primary immunodeficiency caused by mutations in the ITGB2 gene, which encodes for the CD18 subunit of β₂-integrins. Deficient expression of β₂-integrins results in impaired neutrophil migration in response to bacterial and fungal infections. Using a lentiviral vector (LV) that mediates a preferential myeloid expression of human CD18 (Chim.hCD18-LV), we first demonstrated that gene therapy efficiently corrected the phenotype of mice with severe LAD-I. Next, we investigated if the ectopic hCD18 expression modified the phenotypic characteristics of human healthy donor hematopoietic stem cells and their progeny. Significantly, transduction of healthy CD34⁺ cells with the Chim.hCD18-LV did not modify the m

SUBMITTER: Mesa-Nunez C 

PROVIDER: S-EPMC9418989 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature