Closing the gap: Nonviral TFAMoplex transfection boosted by bZIP domains compared to AAV-mediated transduction.

ABSTRACT: The TFAMoplex is a nanoparticulate gene delivery system based on the mitochondrial transcription factor A (TFAM) protein, which can be engineered with various functional domains to enhance plasmid DNA transfection. In this study, we aimed at improving the TFAMoplex system by incorporating basic leucine zipper (bZIP) domains, derived from the cyclic AMP (cAMP)-responsive element-binding protein (CREB), which are known to bind DNA upon dimerization. Additionally, we screened bZIP domains of other proteins (i.e., transcription regulator protein BACH1, cyclic AMP-dependent transcription factor ATF-3, and basic leucine zipper transcriptional factor ATF-like BATF) under challenging transfection conditions, identifying the bZIP domain of BACH1, bZIP_BACH1, as particularly effective in e

SUBMITTER: Honrath S 

PROVIDER: S-EPMC12018551 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature