With substantial advances in the previous decade, conventional gene therapy has proven an effective, curative treatment method for many basic immunological deficiencies. However, there is still a danger of leukemic transformation with viral-mediated gene addition, and uncontrolled gene addition is not an option for some illnesses where the target gene is tightly regulated. The current explosion in genome modification platforms has made it possible to repair defective DNA base pairs or introduce a corrected cDNA minigene while keeping gene expression under the control of endogenous regulatory components. There are many ongoing research projects that are using programme-based nucleases to make it easier for site-specific gene correction of a number of primary immune impairments, such as x-related serious combination immune deficiency, x-related granulomatous disease, Wiscott–Aldrich syndrome, hyper-IgM syndrome, x‐related agammaglobulinemia and immune dysregulation, polyendocrinopathy, enteropathy, x-related disease. In all, these investigations have shown that corrected DNA sequences can be integrated precisely at rates in the genome likely to cure or enhance the illness.
Primary immune deficiency gene editing (PID) has progressed to the extent that it is anticipated that clinical trials will take place within the next several years. Targeted genome alteration provides the next phase of gene therapy for PID given the current pace of research into DNA processes, stem cell biology and genome-editing technologies.
