Moreira Luís, Guimarães Nuno M, Santos Rita S, Loureiro Joana A, Pereira Maria C, Azevedo Nuno F
LEPABE-Laboratory for Process Engineering, Environment, Biotechnology, and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal.
ALiCE-Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal.
Mol Ther Nucleic Acids. 2024 Jan 18;35(1):102122. doi: 10.1016/j.omtn.2024.102122. eCollection 2024 Mar 12.
Antimicrobial resistance (AMR) is a growing concern because it causes microorganisms to develop resistance to drugs commonly used to treat infections. This results in increased difficulty in treating infections, leading to higher mortality rates and significant economic effects. Investing in new antimicrobial agents is, therefore, necessary to prevent and control AMR. Antimicrobial nucleic acids have arisen as potential key players in novel therapies for AMR infections. They have been designed to serve as antimicrobials and to act as adjuvants to conventional antibiotics or to inhibit virulent mechanisms. This new category of antimicrobial drugs consists of antisense oligonucleotides and oligomers, DNAzymes, and transcription factor decoys, differing in terms of structure, target molecules, and mechanisms of action. They are synthesized using nucleic acid analogs to enhance their resistance to nucleases. Because bacterial envelopes are generally impermeable to oligonucleotides, delivery into the cytoplasm typically requires the assistance of nanocarriers, which can affect their therapeutic potency. Given that numerous factors contribute to the success of these antimicrobial drugs, this review aims to provide a summary of the key advancements in the use of oligonucleotides for treating bacterial infections. Their mechanisms of action and the impact of factors such as nucleic acid design, target sequence, and nanocarriers on the antimicrobial potency are discussed.
抗菌药物耐药性（AMR）日益引起人们的关注，因为它会使微生物对常用于治疗感染的药物产生耐药性。这导致治疗感染的难度增加，进而导致更高的死亡率和重大的经济影响。因此，投资研发新型抗菌药物对于预防和控制AMR是必要的。抗菌核酸已成为AMR感染新型疗法中的潜在关键参与者。它们被设计用作抗菌剂，并作为传统抗生素的佐剂或抑制致病机制。这类新型抗菌药物包括反义寡核苷酸和寡聚物、脱氧核酶和转录因子诱饵，它们在结构、靶分子和作用机制方面存在差异。它们使用核酸类似物合成，以增强其对核酸酶的抗性。由于细菌包膜通常对寡核苷酸不可渗透，因此将其递送至细胞质通常需要纳米载体的协助，而这可能会影响它们的治疗效力。鉴于众多因素影响这些抗菌药物的成功应用，本综述旨在总结寡核苷酸用于治疗细菌感染的关键进展。文中讨论了它们的作用机制以及核酸设计、靶序列和纳米载体等因素对抗菌效力的影响。
