Overcoming limitations and advancing the therapeutic potential of antibody-oligonucleotide conjugates (AOCs): Current status and future perspectives

IF 9.1 2区医学 Q1 PHARMACOLOGY & PHARMACY Pharmacological research Pub Date : 2024-10-19 DOI:10.1016/j.phrs.2024.107469

Jinlan Jiao , Yun Qian , Yinhua Lv , Wenqian Wei , Yongxuan Long , Xiaoling Guo , Anya Buerliesi , Jiahui Ye , Hao Han , Jinbo Li , Yun Zhu , Weijie Zhang

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Abstract

As cancer incidence rises due to an aging population, the importance of precision medicine continues to grow. Antibody-drug conjugates (ADCs) exemplify targeted therapies by delivering cytotoxic agents to specific antigens. Building on this concept, researchers have developed antibody-oligonucleotide conjugates (AOCs), which combine antibodies with oligonucleotides to regulate gene expression. This review highlights the mechanism of AOCs, emphasizing their unique ability to selectively target and modulate disease-causing proteins. It also explores the components of AOCs and their application in tumor therapy while addressing key challenges such as manufacturing complexities, endosomal escape, and immune response. The article underscores the significance of AOCs in precision oncology and discusses future directions, highlighting their potential in treating cancers driven by genetic mutations and abnormal protein expression.

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克服抗体-寡核苷酸共轭物 (AOC) 的局限性并提高其治疗潜力：现状与未来展望》。

随着人口老龄化导致癌症发病率上升，精准医疗的重要性与日俱增。抗体-药物共轭物（ADCs）通过向特定抗原递送细胞毒剂，是靶向疗法的典范。在这一概念的基础上，研究人员开发出了抗体-寡核苷酸共轭物（AOCs），它将抗体与寡核苷酸结合起来以调节基因表达。本综述将重点介绍 AOCs 的作用机制，强调其选择性靶向和调节致病蛋白的独特能力。文章还探讨了 AOCs 的成分及其在肿瘤治疗中的应用，同时探讨了制造复杂性、内体逸出和免疫反应等关键挑战。文章强调了 AOCs 在精准肿瘤学中的重要意义，并讨论了未来的发展方向，突出了它们在治疗由基因突变和异常蛋白表达驱动的癌症方面的潜力。

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

Pharmacological research 医学-药学

CiteScore

18.70

自引率

3.20%

发文量

491

审稿时长

8 days

期刊介绍： Pharmacological Research publishes cutting-edge articles in biomedical sciences to cover a broad range of topics that move the pharmacological field forward. Pharmacological research publishes articles on molecular, biochemical, translational, and clinical research (including clinical trials); it is proud of its rapid publication of accepted papers that comprises a dedicated, fast acceptance and publication track for high profile articles.