一种基于优化肽接头的多价CD301融合蛋白、功能化磁珠及其在CTC捕获中的应用

By optimizing the peptide linker design of the multivalent CD301 fusion protein, the problems of EpCAM-dependent missed detection and insufficient stability in existing CTC capture technologies have been solved, achieving efficient and stable capture of EMT-type CTCs, with significantly improved capture efficiency and stability.

CN121991252BActive Publication Date: 2026-07-17CHONGQING ZHENJIAYI BIOTECHNOLOGY CO LTD

Patent Information

Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
CHONGQING ZHENJIAYI BIOTECHNOLOGY CO LTD
Filing Date
2026-04-09
Publication Date
2026-07-17

AI Technical Summary

Technical Problem

Existing CTC capture technologies that rely on EpCAM antibodies have the problem of missing interstitial CTCs. Furthermore, CD301 monomers have weak affinity, complex polymerization design, and poor linker design, leading to instability in the blood environment.

Method used

By employing an optimized peptide linker design, multiple CD301 CRD domains are tandemly linked through genetic engineering and connected using flexible linkers (GGGGS) and rigid linkers (hCGβ CTP) to achieve multivalent chelation effects and enhance stability in the blood environment.

Benefits of technology

It achieves efficient capture of CTCs with different phenotypes, especially EMT-type CTCs, with a capture efficiency of up to 92.8%. It also significantly improves stability in the blood environment, prolongs the half-life, and avoids protease degradation.

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Abstract

本发明涉及生物医学检测技术领域,公开了一种基于优化肽接头的多价CD301融合蛋白、功能化磁珠及其在CTC捕获中的应用,该蛋白为单一多肽链结构,包含通过肽接头串联连接的多个CD301碳水化合物识别域,优选为四聚体形式。本发明对连接各个识别域的肽接头进行了特殊设计,包括优化的柔性接头或富含O‑糖基化位点的刚性接头(如hCGβ CTP),以调控结构域的空间取向。通过将该定向排列的多价蛋白固定于磁性微粒表面,利用多价协同效应显著增强了与肿瘤细胞表面Tn抗原的结合亲合力。本发明的方法能够有效捕获发生上皮‑间质转化(EMT)的低EpCAM表达CTC,且在血液流体剪切力下具有极高的结合稳定性。
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