Targeted Gene Therapy in the Treatment of X-Linked Hyper IgM Syndrome

Abstract

X-linked hyper-IgM syndrome (XHIM) is a primary immunodeficiency due to defects in immunoglobulin class switch recombination caused by mutations in the CD40 ligand (CD40L) gene. Previous gene therapy-based studies have investigated the use of retroviral vectors for delivery of CD40L cDNA. Due to uncontrolled expression of the gene, this method resulted in significant abnormal lymphoproliferation in mouse models, emphasizing the need for alternative strategies. Site-specific genome modification provides the promise for correction of the gene under the regulation of its endogenous enhancer and promoter.

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