Prospects for antisense agents in the therapy of bacterial infections.
Antisense agents have received widespread interest as potential therapeutic agents for a number of diseases, including cancer, inflammatory conditions and viral infections. However, less emphasis has been placed on their potential application in the therapy of bacterial infections. This review considers the reported effects of backbone modified oligonucleotides (phosphorothioate and methyl phosphonate analogues) as well as peptide nucleic acids (PNAs) on gene expression and bacterial growth. In addition to suppressing bacterial growth by decreasing the expression of essential genes, it is also evident that antisense agents can be specifically targeted to genes that control expression of antibiotic resistance mechanisms, thereby potentially restoring an antibiotic-sensitive phenotype to the cell. Despite observations from several studies that antisense agents can interfere with bacterial gene expression in a sequence specific manner, their uptake into bacteria is poor. At present this is a limiting factor in their potential application as therapeutic agents for bacterial infections.
Antimicrobial Research Centre, University of Leeds, Leeds LS2 9JT, United Kingdom. i.chopra@leeds.ac.uk
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