Hyper-IgE-syndrome is a rare primary immunodeficiency characterized by recurrent cutaneous and pulmonary abscesses, elevated IgE serum levels, absence of Th17 cells and a deteriorating quality of life. The disease-causing mutations in patients are usually heterozygous and mainly found in the DNA-binding or the SH2-dimerization domains of STAT3. Mutations in these domains interfere with STAT3’s function as a transcription factor and impede the activation of downstream target gene expression, such as SOCS3. In a proof-of-concept study, we have demonstrated that base editing can lead to a functional rescue of patient T cells. However, this approach is restricted to the underlying point mutation and only beneficial for a few patients. Thus, the present study explored a more universal approach based on the introduction of a corrective STAT3 cDNA at the endogenous locus. To investigate the impact of the integration site, we designed nucleases targeting either intron 7 or exon 8 of STAT3 and integrated a GFP cassette into these sites. Treated K562 cells showed stable GFP expression over time, with a maximum of 10% GFP-positive cells when targeting the intronic site and 30% when integrating into exon 8. Further, we evaluated performance of two different repair template designs, comprising a STAT3 cDNA with either one or six introns. Based on the expression levels of STAT3 and the activation of SOCS3 upon cell stimulation, our preliminary data suggest beneficial effects of integrating a STAT3 cDNA separated by multiple introns. Overall, this all-in-one approach could correct over 90% of all mutations in HIES patients.