Rett syndrome (RTT) is a severe X-linked progressive neurodevelopmental disorder that primarily affects females in early childhood. Although the FDA has approved the first drug treatment for RTT, no curative therapy is currently available. Precision genome editing technologies—particularly CRISPR-based adenine base editing (ABE)—offer a promising strategy for the permanent correction of pathogenic MECP2 mutations, the primary genetic cause of RTT. This thesis explores the use of an imperfect guide RNA (igRNA) strategy incorporating internal barcodes to reduce bystander editing while maintaining high on-target editing efficiency. The approach demonstrated robust editing performance and laid the groundwork for validation in patient-derived fibroblasts and relevant mouse models. These findings highlight a potentially curative genome editing strategy for RTT that can be extended to several of the most prevalent MECP2 mutations. Furthermore, this work supports the broader application of compact ABEs for the treatment of additional central nervous system (CNS) disorders.