IL2RG and severe combined immunodeficiency: For gene therapy, integrating viral vectors carries a risk of insertional mutagenesis; for example, five X-linked severe combined immunodeficiency (SCID-X1) patients successfully treated with ex vivo retroviral interleukin 2 receptor subunit gamma (IL2RG) gene therapy developed T-cell leukemia, and four harbored insertional mutations at LMO2, a known T-cell oncogene [5]; furthermore, pre-existing neutralizing antibodies against AAV capsids occur in approximately 30–60% of individuals, significantly reducing transduction efficiency [6].