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.
Highlights
The antisense RNA mechanism comprises all forms of sequence-specific messenger RNA (mRNA) recognition leading to reduced or altered expression of a certain transcript [1]
Occurring antisense RNA (asRNA) are found in all three kingdoms of life, most examples are found in bacteria, and they affect messenger RNA destruction, repression and activation as well as RNA processing and transcription [2]
The annealing of antisense molecules to either mRNAs or functional RNAs can result in fast degradation of duplex RNA, hybrid RNA/DNA duplex, or duplex RNA resembling precursor tRNA by ribonucleases in the cell, or by cleavage of the target RNA by the antisense compound itself
Summary
The antisense RNA (asRNA) mechanism comprises all forms of sequence-specific mRNA recognition leading to reduced or altered expression of a certain transcript [1]. Occurring asRNAs are found in all three kingdoms of life, most examples are found in bacteria, and they affect messenger RNA (mRNA) destruction, repression and activation as well as RNA processing and transcription [2] This mechanism can be exploited in engineering strategies for inhibiting protein synthesis. Microbial Cell Factories 2007, 6:24 http://www.microbialcellfactories.com/content/6/1/24 hindrance of either ribosome access or ribosomal readthrough (Fig. 1) This inhibition mechanism is, specific for mRNAs. The annealing of antisense molecules to either mRNAs or functional RNAs can result in fast degradation of duplex RNA, hybrid RNA/DNA duplex, or duplex RNA resembling precursor tRNA by ribonucleases in the cell, or by cleavage of the target RNA by the antisense compound itself. Antisense molecules and methods have been developed and designed to address these issues and improve the inhibitory efficiency These antisense strategies will be presented as well as recent studies describing their application. An RNAinterference-based immune system in prokaryotes has been proposed recently [8,9], but a technology exploiting this finding for the sequence-specific inhibition of bacterial proliferation has still to be developed
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