Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Izmir Katip Celebi University, Izmir, Türkiye.
Nucleosides Nucleotides Nucleic Acids. 2024;43(1):1-39. doi: 10.1080/15257770.2023.2228841. Epub 2023 Jul 3.
Infectious diseases have been one of the biggest health problems of humanity for centuries. Nucleic acid-based therapeutics have received attention in recent years with their effectiveness in the treatment of various infectious diseases and vaccine development studies. This review aims to provide a comprehensive understanding of the basic properties underlying the mechanism of antisense oligonucleotides (ASOs), their applications, and their challenges. The efficient delivery of ASOs is the greatest challenge for their therapeutic success, but this problem is overcome with new-generation antisense molecules developed with chemical modifications. The types, carrier molecules, and gene regions targeted by sequences have been summarized in detail. Research and development of antisense therapy is still in its infancy; however, gene silencing therapies appear to have the potential for faster and longer-lasting activity than conventional treatment strategies. On the other hand, realizing the potential of antisense therapy will require a large initial economic investment to ascertain the pharmacological properties and learn how to optimize them. The ability of ASOs to be rapidly designed and synthesized to target different microbes can reduce drug discovery time from 6 years to 1 year. Since ASOs are not particularly affected by resistance mechanisms, they come to the fore in the fight against antimicrobial resistance. The design-based flexibility of ASOs has enabled it to be used for different types of microorganisms/genes and successful and results have been revealed. The current review summarized a comprehensive understanding of ASO therapy in combating bacterial and viral infections.
传染病是几个世纪以来人类面临的最大健康问题之一。近年来,核酸类药物因其在治疗各种传染病和疫苗开发研究中的有效性而受到关注。本综述旨在全面了解反义寡核苷酸(ASO)的基本特性、它们的应用及其面临的挑战。ASO 的高效递送是其治疗成功的最大挑战,但通过开发具有化学修饰的新一代反义分子,这一问题得到了克服。本文详细总结了序列的类型、载体分子和靶向基因区域。反义疗法的研究和开发仍处于起步阶段;然而,基因沉默疗法似乎比传统治疗策略具有更快和更持久的活性的潜力。另一方面,要实现反义疗法的潜力,需要进行大量的初始经济投资,以确定其药理学特性并学习如何优化这些特性。ASO 能够快速设计和合成以针对不同微生物的能力,可以将药物发现时间从 6 年缩短至 1 年。由于 ASO 不太受耐药机制的影响,因此在对抗抗微生物药物耐药性方面具有优势。ASO 的基于设计的灵活性使其能够用于不同类型的微生物/基因,并已取得成功的结果。本综述总结了对 ASO 疗法在防治细菌和病毒感染方面的全面认识。