PEMax

PEMax is an optimized prime editing (PE) architecture designed to enhance the efficiency of precise genome modifications. Developed as an improvement over the original PE2 system, PEMax incorporates codon optimization of the editor components and the addition of nuclear localization signals to maximize nuclear import and activity. In the context of Duchenne Muscular Dystrophy (DMD) research, PEMax is utilized within a "Twin Prime Editing" framework—employing two prime editing guide RNAs (pegRNAs)—to induce large-scale genomic deletions or insertions. This specific application aims to correct N-terminal mutations in the DMD gene by restoring the reading frame or enabling the expression of functional dystrophin isoforms, such as those driven by internal ribosome entry sites (IRES). While standard PEMax typically utilizes a Cas9 nickase, specific therapeutic approaches for DMD have employed a modified version with full Cas9 activity to improve the efficiency of large deletions.