Optimized RAG1 deficient gene therapy

The present invention provides novel expression cassettes, retroviral plasmids, vectors, virions, compositions and recombinant cells comprising a promoter operably linked to a codon optimized 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-1gene, such as RAG-deficient severe combined immunodeficiency (RAG1-SCID),Omenn Syndrome (OS), atypical-SCID or combined immunodeficiency (CID). The invention also provides corresponding methods of treatment. 本发明提供了新型表达盒、逆转录病毒质粒、载体、病毒粒子、组合物和重组细胞，其包含与密码子优化的重组激活(RAG1)转基因可操作连接的启动子。这些新型表达盒、逆转录病毒质粒、载体、病毒粒子、组合物和重组细胞适用于治疗由rag-1基因编码的蛋白质的完全或部分功能丧失引起的疾病，如RAG缺陷型严重联合免疫缺陷症(RAG1-SCID)、Omenn综合征(OS)、非典型SCID或联合免疫缺陷症(CID)。本发明还提供了相应的治疗方法。