Malinowska Anna L, Huynh Harley L, Bose Sritama
Medical Research Council, Nucleic Acid Therapy Accelerator (UKRI), Research Complex at Harwell (RCaH), Rutherford Appleton Laboratory, Harwell OX11 0FA, UK.
Curr Issues Mol Biol. 2024 Sep 30;46(10):11031-11047. doi: 10.3390/cimb46100655.
Oligonucleotides have been identified as powerful therapeutics for treating genetic disorders and diseases related to epigenetic factors such as metabolic and immunological dysfunctions. However, they face certain obstacles in terms of limited delivery to tissues and poor cellular uptake due to their large size and often highly charged nature. Peptide-oligonucleotide conjugation is an extensively utilized approach for addressing the challenges associated with oligonucleotide-based therapeutics by improving their delivery, cellular uptake and bioavailability, consequently enhancing their overall therapeutic efficiency. In this review, we present an overview of the conjugation of oligonucleotides to peptides, covering the different strategies associated with the synthesis of peptide-oligonucleotide conjugates (POC), the commonly used peptides employed to generate POCs, with the aim to develop oligonucleotides with favourable pharmacokinetic (PK) or pharmacodynamic (PD) properties for therapeutic applications. The advantages and drawbacks of the synthetic methods and applications of POCs are also described.
寡核苷酸已被确认为治疗遗传疾病以及与表观遗传因素相关疾病（如代谢和免疫功能障碍）的有效疗法。然而，由于其较大的尺寸和通常较高的电荷性质，它们在向组织的递送受限和细胞摄取较差方面面临某些障碍。肽 - 寡核苷酸缀合是一种广泛应用的方法，通过改善寡核苷酸的递送、细胞摄取和生物利用度来应对基于寡核苷酸的疗法所面临的挑战，从而提高其整体治疗效率。在这篇综述中，我们概述了寡核苷酸与肽的缀合，涵盖了与肽 - 寡核苷酸缀合物（POC）合成相关的不同策略、用于生成POC的常用肽，旨在开发具有有利药代动力学（PK）或药效学（PD）特性的寡核苷酸用于治疗应用。还描述了POC合成方法和应用的优缺点。
