Recent Advances in Peptide Nucleic Acids as Antibacterial Agents.

The emergence of antibiotic-resistant bacteria and the slow progress in searching for new antimicrobial agents makes it hard to treat bacterial infections and cause problems for the healthcare system worldwide, including high costs, prolonged hospitalizations, and increased mortality. Therefore, the discovery of effective antibacterial agents is of great importance. One attractive alternative is antisense peptide nucleic acid (PNA), which inhibits or eliminates gene expression by binding to the complementary messenger RNA (mRNA) sequence of essential genes or the accessible and functionally important regions of the ribosomal RNA (rRNA). Following 30 years of development, PNAs have played an extremely important role in the treatment of Gram-positive, Gram-negative, and acidfast bacteria due to their desirable stability of hybrid complex with target RNA, the strong affinity for target mRNA/rRNA, and the stability against nucleases. PNA-based antisense antibiotics can strongly inhibit the growth of pathogenic and antibiotic-resistant bacteria in a sequence-specific and dose-dependent manner at micromolar concentrations. However, several fundamental challenges, such as intracellular delivery, solubility, physiological stability, and clearance still need to be addressed before PNAs become broadly applicable in clinical settings. In this review, we summarize the recent advances in PNAs as antibacterial agents and the challenges that need to be overcome in the future.

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