Peptide-Oligonucleotide Conjugation: Chemistry and Therapeutic Applications.

IF 2.8 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current Issues in Molecular Biology Pub Date : 2024-09-30 DOI:10.3390/cimb46100655

Anna L Malinowska, Harley L Huynh, Sritama Bose

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Abstract

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.

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肽-寡核苷酸共轭：化学与治疗应用》。

寡核苷酸已被确定为治疗遗传性疾病和与表观遗传因素有关的疾病（如代谢和免疫功能障碍）的强大疗法。然而，由于寡核苷酸体积大且通常带高电荷，它们在向组织输送方面受到限制，而且细胞吸收率低，因此面临着一些障碍。肽-寡核苷酸共轭是一种广泛应用的方法，可通过改善寡核苷酸疗法的递送、细胞摄取和生物利用度来应对相关挑战，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共轭，涵盖了与肽-寡核苷酸共轭物（POC）合成相关的不同策略，以及用于生成 POC 的常用肽，目的是开发出具有良好药代动力学（PK）或药效学（PD）特性的寡核苷酸，用于治疗应用。此外，还介绍了 POCs 合成方法和应用的优缺点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current Issues in Molecular Biology 生物-生化研究方法

CiteScore

2.90

自引率

3.20%

发文量

380

审稿时长

>12 weeks

期刊介绍： Current Issues in Molecular Biology (CIMB) is a peer-reviewed journal publishing review articles and minireviews in all areas of molecular biology and microbiology. Submitted articles are subject to an Article Processing Charge (APC) and are open access immediately upon publication. All manuscripts undergo a peer-review process.