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.

抗生素抗性细菌的出现以及寻找新的抗菌剂的进展缓慢，使细菌感染的治疗变得困难，并给全世界的医疗系统造成了问题，包括高成本，长期住院和增加死亡率。因此，发现有效的抗菌剂非常重要。一种有吸引力的替代方案是反义肽核酸（PNA），它通过结合必需基因的互补信使RNA（mRNA）序列或核糖体RNA（rRNA）的可及功能重要区域来抑制或消除基因表达。经过30年的发展，PNA在革兰氏阳性，革兰氏阴性，和耐酸细菌，因为它们具有与目标RNA的杂合体所需的稳定性，对目标mRNA / rRNA的强亲和力以及对核酸酶的稳定性。基于PNA的反义抗生素可以在微摩尔浓度下以序列特异性和剂量依赖性方式强烈抑制病原性和抗生素抗性细菌的生长。但是，在PNA广泛应用于临床之前，仍然需要解决一些基本挑战，例如细胞内递送，溶解性，生理稳定性和清除性。在这篇综述中，我们总结了作为抗菌剂的PNA的最新进展以及未来需要克服的挑战。基于PNA的反义抗生素可以在微摩尔浓度下以序列特异性和剂量依赖性方式强烈抑制病原性和抗生素抗性细菌的生长。但是，在PNA广泛应用于临床之前，仍然需要解决一些基本挑战，例如细胞内递送，溶解性，生理稳定性和清除性。在这篇综述中，我们总结了作为抗菌剂的PNA的最新进展以及未来需要克服的挑战。基于PNA的反义抗生素可以在微摩尔浓度下以序列特异性和剂量依赖性方式强烈抑制病原性和抗生素抗性细菌的生长。但是，在PNA广泛应用于临床之前，仍然需要解决一些基本挑战，例如细胞内递送，溶解性，生理稳定性和清除性。在这篇综述中，我们总结了作为抗菌剂的PNA的最新进展以及未来需要克服的挑战。在PNA广泛应用于临床之前，仍然需要解决通关问题。在这篇综述中，我们总结了作为抗菌剂的PNA的最新进展以及未来需要克服的挑战。在PNA广泛应用于临床之前，仍然需要解决清除问题。在这篇综述中，我们总结了作为抗菌剂的PNA的最新进展以及未来需要克服的挑战。