Antisense antibacterials

Bacterial infections and antibacterial resistance are long-term problems that call for innovative new therapeutics. Unfortunately, only one truly new antibacterial has reached the market during the last three decades, while resistance trait problems in the clinic continue to increase. Among the possible sources for new antimicrobials, antisense technology brings new chemical classes and access to a wider range of drug targets. Although given little consideration, antisense antibacterials are a rational approach and there has been significant progress in the area. Technical challenges arise from the relatively large size of antisense agents, as this limits cell uptake and distribution. Fortunately, the polymeric sequence nature of antisense agents provides several design and medicinal chemistry options that can be used to improve uptake and, once internalised, the organelle-free bacteria cell interior should allow easy access to attractive nucleic acid targets.