Initial attempts to develop a gene therapy vector for Rett syndrome utilizing wild type or codon-optimized MECP2 under the control of either a heterologous or a minimal MECP2 promoter (Gadalla et al., 2013; Garg et al., 2013; Matagne et al., 2017), conferred modest improvement in lifespan and motor abilities in knockout mice, however, overexpression-related toxicity was encountered. Here, MECP2 is linked to Rett syndrome.