• SAF-A expression level is positively correlated with transgene expression in episomal vectors, as demonstrated by correlation analysis and knockdown/overexpression experiments.
• Knockdown of SAF-A via shRNA significantly reduces eGFP expression, while overexpression of SAF-A enhances transgene expression by over 2-fold, indicating a direct regulatory role.
• The 375 bp MAR characteristic sequence in pEMEα retains functional interaction with SAF-A, supporting its use in compact episomal vectors for gene therapy.
• This study provides a novel strategy to boost transgene expression and stability in non-viral episomal vectors by modulating SAF-A levels, with potential to improve gene therapy efficacy.