Therapeutics: RNA

In vitro studies identified paromomycin analogs that could help treat bacterial infections without aminoglycoside-associated ototoxicity. In a cell-free translation assay, a screen of 4'-O-glycoside analogs of paromomycin identified several compounds that inhibited RNA translation in bacterial ribosomes with IC50 values of 0.03-0.26 μM, but inhibited RNA translation in cytosolic ribosomes from eukaryotic cells and mitochondrial ribosomes, including a mutant mitochondrial ribosome associated with drug-induced ototoxicity, with IC50 values greater than 4 μM. In cultures of multiple strains of Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA), several compounds exhibited comparable minimum inhibitory concentration (MIC) values to paromomycin. Next steps include the formation of a start-up, Juvabis GmbH, to develop the analogs for clinical use...