To address this challenge, Prof. Ki-Bum Lee and his research team (https://kblee.rutgers.edu/) developed a nanoparticle-based synthetic mitochondrial transcription regulator (MitoScript) for effective and selective manipulation of mtDNA transcription by mimicking the functions and structures of mitochondrial transcription factors.
The developed MitoScript platform is constructed from an ultrasmall nanocluster as a fluorescent core, synthetic pyrrole imidazole polyamide (PIP) oligomers as mtDNA binding domains for site-specific transcription regulation, and mitochondria-penetrating peptides (MPPs) as mitochondrial localization domains. Notably, MitoScript controlled mtDNA transcription in a human cell line in an effective and selective manner. Furthermore, MitoScript provides great colloidal stability, excellent biocompatibility, efficient cell uptake, and selective mitochondria targeting and can be monitored in live cells using near-infrared fluorescence.
In short, inspired by the multidomain structure of natural transcription factors, the ultrasmall nanoparticle-based MitoScript was designed and synthesized to manipulate mitochondrial gene transcription effectively. Furthermore, the MitoScript platform technologycan be applied to further develop effective treatments for mitochondrial diseases by targeting specific genetic mutations and providing a novel approach to understanding the underlying mechanisms of mitochondrial disorders. By leveraging the power of gene editing technologies, this platform may provide a way to accurately and efficiently modify mitochondrial genomes, ultimately leading to improved treatments for mitochondrial diseases.
PUBLICATION: Letao Yang, Christopher Rathnam, Takuya Hidaka, Yannan Hou, Brandon Conklin, Ganesh N. Pandian, Hiroshi Sugiyama, and Ki-Bum Lee. Nano Letters, 2023, DOI:10.1021/acs.nanolett.2c03958