Multivalent Aptamer-Based Lysosome-Targeting Chimeras (LYTACs) Platform for Mono- or Dual-Targeted Proteins Degradation on Cell Surface,Advanced Science

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Multivalent Aptamer-Based Lysosome-Targeting Chimeras (LYTACs) Platform for Mono- or Dual-Targeted Proteins Degradation on Cell Surface
Advanced Science ( IF 14.3 ) Pub Date : 2024-02-29 , DOI: 10.1002/advs.202308924
Qiao Duan ₁ , Hao-Ran Jia _{1,

2} , Weichang Chen ₂ , Chunhong Qin ₂ , Kejing Zhang _{2,

3} , Fei Jia ₂ , Ting Fu ₂ , Yong Wei ₂ , Mengyang Fan ₂ , Qin Wu ₂ , Weihong Tan _{1,

2}

Affiliation

Selective protein degradation platforms have opened novel avenues in therapeutic development and biological inquiry. Antibody-based lysosome-targeting chimeras (LYTACs) have emerged as a promising technology that extends the scope of targeted protein degradation to extracellular targets. Aptamers offer an advantageous alternative owing to their potential for modification and manipulation toward a multivalent state. In this study, a chemically engineered platform of multivalent aptamer-based LYTACs (AptLYTACs) is established for the targeted degradation of either single or dual protein targets. Leveraging the biotin-streptavidin system as a molecular scaffold, this investigation reveals that trivalently mono-targeted AptLYTACs demonstrate optimum efficiency in degrading membrane proteins. The development of this multivalent AptLYTACs platform provides a principle of concept for mono-/dual-targets degradation, expanding the possibilities of targeted protein degradation.

中文翻译：

基于多价适体的溶酶体靶向嵌合体 (LYTAC) 平台，用于细胞表面的单或双靶向蛋白质降解

选择性蛋白质降解平台为治疗开发和生物学研究开辟了新途径。基于抗体的溶酶体靶向嵌合体（LYTAC）已成为一项有前途的技术，它将靶向蛋白质降解的范围扩展到细胞外靶点。适体提供了一种有利的替代方案，因为它们具有修饰和操纵多价状态的潜力。在这项研究中，建立了基于多价适体的 LYTAC（AptLYTAC）的化学工程平台，用于单或双蛋白质靶标的靶向降解。这项研究利用生物素-链霉亲和素系统作为分子支架，表明三价单靶向 AptLYTAC 在降解膜蛋白方面表现出最佳效率。这种多价 AptLYTACs 平台的开发为单/双靶点降解提供了概念原则，扩大了靶向蛋白质降解的可能性。

更新日期：2024-02-29

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