Abstract: The present invention provides novel expression cassettes, retroviral plasmids, vectors, virions, compositions and recombinant cells comprising a promoter operably linked to a codon optimised recombination activating (RAG1) transgene. These novel expression cassettes, retroviral plasmids, vectors, virions, compositions and recombinant cells are useful in the treatment of diseases caused by complete or partial loss-of-function of the protein encoded by the rag-1 gene, such as RAG-deficient severe combined immunodeficiency (RAG1-SCID), Omenn Syndrome (OS), atypical-SCID or combined immunodeficiency (CID). Corresponding methods of treatment are also provided.