A self-inactivating lentiviral vector for SCID-X1 gene therapy that does not activate LMO2 expression in human T cells

To develop safer and more effective vectors for gene therapy of X-linked severe combined immunodeficiency (SCID-X1), we have evaluated new self-inactivating lentiviral vectors based on the HIV virus. The CL20i4-hc-Revgen vector contains the entire human common chain (c) genomic sequence driven by the c promoter. The CL20i4-EF1-hcOPT vector uses a promoter fragment from the eukaryotic elongation factor alpha (EF1) gene to express a codon-optimized human c cDNA. Both vectors contain a 400-bp insulator fragment from the chicken β-globin locus within the self-inactivating long-terminal repeat. Transduction of bone marrow cells using either of these vectors restored T, B, and natural killer lymphocyte development and function in a mouse SCID-X1 transplantation model. Transduction of human …