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Abstract：
Although recent advancements in cancer immunology have resulted in the approval of numerous immunotherapies, minimal progress has been observed in addressing hard-to-treat cancers. In this context, therapeutic oligonucleotides, including interfering RNAs, antisense oligonucleotides, aptamers, and DNAzymes, have gained a central role in cancer therapeutic approaches due to their capacity to regulate gene expression and protein function with reduced toxicity compared with conventional chemotherapeutics. Nevertheless, systemic administration of naked oligonucleotides faces many extra- and intracellular challenges that can be overcome by using effective delivery systems. Thus, viral and non-viral carriers can improve oligonucleotide stability and intracellular uptake, enhance tumor accumulation, and increase the probability of endosomal escape while minimizing other adverse effects. Therefore, gaining more insight into fundamental mechanisms of actions of various oligonucleotides and the challenges posed by naked oligonucleotide administration, this article provides a comprehensive review of the recent progress on oligonucleotide delivery systems and an overview of completed and ongoing cancer clinical trials that can shape future oncological treatments.
摘要：
尽管癌症免疫学的最新进展已导致许多免疫疗法的批准，在解决难以治疗的癌症方面进展甚微.在这种情况下，治疗性寡核苷酸，包括干扰RNA，反义寡核苷酸,适体,和DNA酶，与常规化学疗法相比，由于其调节基因表达和蛋白质功能的能力而具有降低的毒性，因此在癌症治疗方法中发挥了核心作用。然而，全身施用裸寡核苷酸面临许多可以通过使用有效递送系统克服的细胞外和细胞内挑战。因此，病毒和非病毒载体可以提高寡核苷酸的稳定性和细胞内摄取，增强肿瘤积累，并增加内体逃逸的可能性，同时将其他不利影响降至最低。因此,更深入地了解各种寡核苷酸的基本作用机制以及裸寡核苷酸给药带来的挑战，本文对寡核苷酸递送系统的最新进展进行了全面综述，并概述了可以影响未来肿瘤治疗的已完成和正在进行的癌症临床试验。
