Oligonucleotide-based agents are versatile biomolecules that modulate gene expression. The last decade has seen the emergence of oligonucleotide-based tools for biochemical investigations. Importantly, several oligonucleotide-based drugs and vaccines are currently used for various therapeutic applications ranging from anti-inflammatory and anti-viral agents to those used in cardiovascular, ophthalmic, and neuro-muscular disorders. Despite a broad range of applications, achieving efficient oligonucleotide delivery remains a major limitation. A possible solution is to conjugate cell-penetrating peptides with oligonucleotides. This review provides an overview of chemical strategies used to synthesise peptide–oligonucleotide conjugates. The merits and liabilities of these strategies are discussed in the context of synthetic efficiency, and bio-reversible and -irreversible linkages.

基于寡核苷酸的试剂是调节基因表达的多功能生物分子。过去十年见证了基于寡核苷酸的生化研究工具的出现。重要的是，目前有几种基于寡核苷酸的药物和疫苗用于各种治疗应用，从抗炎和抗病毒药物到用于心血管、眼科和神经肌肉疾病的药物。尽管应用范围很广，但实现有效的寡核苷酸递送仍然是一个主要限制。一种可能的解决方案是将细胞穿透肽与寡核苷酸结合。本综述概述了用于合成肽-寡核苷酸偶联物的化学策略。这些策略的优点和缺点在综合效率的背景下进行了讨论，