Hitting bacteria at the heart of the central dogma: sequence-specific inhibition |
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Authors: | Louise Carøe Vohlander Rasmussen Hans Uffe Sperling-Petersen Kim Kusk Mortensen |
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Institution: | (1) Laboratory of BioDesign, Department of Molecular Biology, Aarhus University, Gustav Wieds Vej 10 C, DK-8000 Aarhus C, Denmark |
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Abstract: | An important objective in developing new drugs is the achievement of high specificity to maximize curing effect and minimize
side-effects, and high specificity is an integral part of the antisense approach. The antisense techniques have been extensively
developed from the application of simple long, regular antisense RNA (asRNA) molecules to highly modified versions conferring
resistance to nucleases, stability of hybrid formation and other beneficial characteristics, though still preserving the specificity
of the original nucleic acids. These new and improved second- and third-generation antisense molecules have shown promising
results. The first antisense drug has been approved and more are in clinical trials. However, these antisense drugs are mainly
designed for the treatment of different human cancers and other human diseases. Applying antisense gene silencing and exploiting
RNA interference (RNAi) are highly developed approaches in many eukaryotic systems. But in bacteria RNAi is absent, and gene
silencing by antisense compounds is not nearly as well developed, despite its great potential and the intriguing possibility
of applying antisense molecules in the fight against multiresistant bacteria. Recent breakthrough and current status on the
development of antisense gene silencing in bacteria including especially phosphorothioate oligonucleotides (PS-ODNs), peptide
nucleic acids (PNAs) and phosphorodiamidate morpholino oligomers (PMOs) will be presented in this review. |
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