Described herein are systems and methods for treating, inhibiting, or ameliorating X-linked disorders including Wiskott-Aldrich Syndrome (WAS) and X-linked thrombocytopenia (XLT) in subjects that have been identified or selected as being ones that would benefit from a therapy to treat, inhibit, or ameliorate WAS or XLT. The systems include nuclease and vector donor constructs configured for co-delivery to modify endogenous WAS locus.