Antisense Oligonucleotides-Based Therapeutics for Pathogenic Bacteria and Viruses

Human pathogenic bacteria and viruses are significant etiology of different types of infectious diseases that cause extremely high morbidity and mortality worldwide. Continuous failure of anti- pathogen/infective agents and therapies, as well as the paucity of postexposure therapeutics greatly facilitates the emergence and dissemination of pathogenic bacterial isolates and virus phenotypes with multi-drug resistance (MDR) or pan-drug resistance (PDR). Additionally, the potential use of these bacteria and viruses in acts of bioterrorism poses tremendous threat to global security. Novel counterstrike strategy of using single-stranded antisense oligonucleotides (ASOs) as prospective gene silencers has been a major area of anti-infective study, leading a potential revolution in the development of antibacterial and antiviral therapeutics by addressing the targets that are “undruggable” for traditional pharmaceutical approaches. Given 30 years of technology advances in elucidation of antisense mechanism, characterization of ASOs chemical modification, and refinement of delivery systems, ASOs based anti-infective strategy displays advantageous features of conceptual simplicity, straightforward designing and quick drug identification methods. The stericblocking ASOs offer improving sequence-specific anti-infective effects in vitro and in animal models of fatal infections, which enables themselves candidates for pre-clinical and clinical tests. This chapter puts together and discusses the important advances in the field based on the above mentioned technologies and the latest development of potential targets and therapeutic AS-ODNs that have reached clinical trials with antibacterial or antiviral protocols.

Keywords: Acyl carrier protein, antisense antibacterial, antisense antiviral, antisense oligonucleotides therapy, cell penetrating peptide, host factors, liposome, locked nucleic acid, peptide nucleic acid, phosphorodiamidate morpholino oligomers, phosphorothioate, RNA polymerase σ70, RNase H activation, steric-blokcing mechanism.