Leveraging aptamers for targeted protein degradation

Zhihao Yang; Qiuxiang Pang; Jun Zhou; Chenghao Xuan; Songbo Xie

doi:10.1016/j.tips.2023.05.008

Leveraging aptamers for targeted protein degradation

Trends Pharmacol Sci. 2023 Nov;44(11):776-785. doi: 10.1016/j.tips.2023.05.008. Epub 2023 Jun 26.

Authors

Zhihao Yang¹, Qiuxiang Pang², Jun Zhou³, Chenghao Xuan⁴, Songbo Xie⁵

Affiliations

¹ The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Biochemistry and Molecular Biology, Tianjin Medical University, Tianjin, China.
² School of Life Sciences and Medicine, Shandong University of Technology, Zibo, China.
³ Center for Cell Structure and Function, Shandong Provincial Key Laboratory of Animal Resistance Biology, Collaborative Innovation Center of Cell Biology in Universities of Shandong, College of Life Sciences, Shandong Normal University, Jinan, China; Department of Genetics and Cell Biology, State Key Laboratory of Medicinal Chemical Biology, Haihe Laboratory of Cell Ecosystem, College of Life Sciences, Nankai University, Tianjin, China.
⁴ The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Biochemistry and Molecular Biology, Tianjin Medical University, Tianjin, China. Electronic address: chenghaoxuan@tmu.edu.cn.
⁵ School of Life Sciences and Medicine, Shandong University of Technology, Zibo, China; Center for Cell Structure and Function, Shandong Provincial Key Laboratory of Animal Resistance Biology, Collaborative Innovation Center of Cell Biology in Universities of Shandong, College of Life Sciences, Shandong Normal University, Jinan, China. Electronic address: xiesongbo@sdnu.edu.cn.

PMID: 37380531
DOI: 10.1016/j.tips.2023.05.008

Abstract

Targeted protein degradation (TPD) technologies, particularly proteolysis-targeting chimeras (PROTACs), have emerged as a significant advancement in drug discovery. However, several hurdles - such as the difficulty of identifying suitable ligands for traditionally undruggable proteins, poor solubility and impermeability, nonspecific biodistribution, and on-target off-tissue toxicity - present challenges to their clinical applications. Aptamers are promising ligands for broad-ranging molecular recognition. Utilizing aptamers in TPD has shown potential advantages in overcoming these challenges. Here, we provide an overview of recent developments in aptamer-based TPD, emphasizing their potential to achieve targeted delivery and their promise for the spatiotemporal degradation of undruggable proteins. We also discuss the challenges and future directions of aptamer-based TPD with the goal of facilitating their clinical applications.

Keywords: PROTAC; aptamer; spatiotemporal regulation; targeted delivery; targeted protein degradation; undruggable protein.

Publication types

Review