A High-Internalization-Efficiency Aptamer-Based LYTAC Chimera for Enhanced Degradation of Leukemia Cell Membrane Proteins

doi:10.7503/cjcu20260017

Chem. J. Chinese Universities

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A High-Internalization-Efficiency Aptamer-Based LYTAC Chimera for Enhanced Degradation of Leukemia Cell Membrane Proteins

CHEN Zhuoran, GONG Linyu, AI Lili, ZHANG Peng, ZHOU Yanhua

Center for Tissue Engineering and Stem Cell Research, Guizhou Biomanufacturing Laboratory, Key Laboratory of Functional Nucleic Acids-Based Biopharmaceutical Research, Guizhou Medical University

Received:2026-01-08 Revised:2026-03-23 Online First:2026-03-25 Published:2026-03-25
Supported by:
Supported by the National Natural Science Foundation of China(Nos.81960036, 22564008), the Higher Education Institutions Scientific and Technological Innovation Team of Guizhou Province(No.qianjiaoji2023-068) and the Scientific and Technological Fund Program of Guizhou Provincial Health Commission(Nos. gzwkj2021-157, 2024GZWJKJXM0466)

Abstract

Abstract: Acute myeloid leukemia (AML) is an aggressive hematologic malignancy with limited treatment options due to high relapse rates and severe side effects, highlighting the demand for innovative therapeutic approaches. The transferrin receptor 1 (TfR1/CD71), a critical regulator of cellular iron uptake and proliferation, is markedly overexpressed on AML and other leukemia cells, rendering it an attractive therapeutic target. Leveraging lysosome-targeting chimera (LYTAC) technology, we designed and synthesized a novel bifunctional molecule, HG9-10-tri, composed of a high-internalizing CD71-targeting aptamer (HG9) conjugated to the lysosome-directing ligand triacetyl galactosamine (triGalNAc). This chimera enables efficient and specific degradation of CD71 via the asialoglycoprotein receptor (ASGPR)-mediated endolysosomal pathway.

Key words: CD71; Cell membrane degradation, LYTACs, Aptamer, tri-GalNAc (Triacetylgalactosamine)

CLC Number:

R966
O6

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CHEN Zhuoran, GONG Linyu, AI Lili, ZHANG Peng, ZHOU Yanhua. A High-Internalization-Efficiency Aptamer-Based LYTAC Chimera for Enhanced Degradation of Leukemia Cell Membrane Proteins[J]. Chem. J. Chinese Universities, doi: 10.7503/cjcu20260017.

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A High-Internalization-Efficiency Aptamer-Based LYTAC Chimera for Enhanced Degradation of Leukemia Cell Membrane Proteins

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