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Infectious disease

Bacterial infection

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In vitro and rodent studies identified cytoplasmic rRNA-targeted aminoglycoside derivatives that could help treat bacterial infections and certain genetic diseases with fewer side effects than approved aminoglycosides. Aminoglycosides treat bacterial infections and nonsense mutation-associated genetic diseases by binding to bacterial rRNA or eukaryotic cytoplasmic rRNA but cause side effects such as ototoxicity by inhibiting mitochondrial rRNA. In a human cell line, aminoglycoside derivatives with selectivity for cytoplasmic over mitochondrial rRNA caused less oxidative stress and cell death than mitochondria-targeting derivatives. In mouse cochlear explants and in guinea pigs, cytoplasm-targeting aminoglycoside derivatives led to less outer ear hair cell loss. Next steps include assessing therapeutic activity.

SciBX 7(2); doi:10.1038/scibx.2014.56
Published online Jan. 16, 2014

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Shulman, E. et al. J. Biol. Chem.; published online Dec. 3, 2013;
Contact: Timor Baasov, Technion-Israel Institute of Technology, Haifa, Israel