Citation: Di Jiang, Ling Wang, Hengyi Lin, Xiaoqiu Wu, Mingxin Zhang, Songxiao Xu, Zhenhao Long, Tao Bing. Selection and characterization of aptamers against CD38 for clinical diagnostics[J]. Chinese Chemical Letters, ;2026, 37(3): 111502. doi: 10.1016/j.cclet.2025.111502 shu

Selection and characterization of aptamers against CD38 for clinical diagnostics

Di Jiang ^{a, b} ,
Ling Wang ^{a, b} ,
Hengyi Lin ^b ,
Xiaoqiu Wu ^b ,
Mingxin Zhang ^b ,
Songxiao Xu ^b ,
Zhenhao Long ^{b, *,} ,
Tao Bing ^{b, c, d, e, *,}

a.
Zhejiang University of Technology, Hangzhou 310014, China
b.
Zhejiang Cancer Hospital, The Key Laboratory of Zhejiang Province for Aptamers and Theranostics, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China
c.
Eye Research Center, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Eye Hospital, Wenzhou Medical University, Hangzhou 310018, China
d.
School of Molecular Medicine, Hangzhou Institute for Advanced Study, UCAS, Hangzhou 310024, China
e.
University of Chinese Academy of Sciences, Beijing 100049, China

longzhenhao@him.cas.cn

bingtao@him.cas.cn

Received Date: 4 January 2025
Revised Date: 30 April 2025
Accepted Date: 24 June 2025
Available Online: 25 June 2025

Figures(5)

Multiple myeloma (MM) is a highly aggressive hematologic malignancy characterized by abnormal proliferation of malignant plasma cells. CD38, a transmembrane glycoprotein, is highly expressed on the surface of plasma cells and serves as a critical diagnostic and therapeutic target for MM. However, the masking of CD38 epitopes caused by therapeutic interventions often leads to false-negative results in clinical detection of CD38, compromising diagnostic accuracy and underscoring the urgent need for novel specific molecular tools. Herein, we reported a novel aptamer, CD38jd4a, specifically targeting CD38 with potential clinical applications. A series of high-affinity aptamers specifically binding CD38 were selected and identified through a highly efficient aptamer selection method with CD38 as the target. Among them, aptamer CD38jd4a exhibited the best performance, with a dissociation constant (K_d) value as low as 5.4 ± 0.6 nmol/L. Through siRNA-mediated knockdown experiments, CD38jd4a was further validated to specifically recognize native CD38 expressed on surface of cells. Furthermore, binding epitopes of CD38jd4a were confirmed to be distinct from those recognized by any of current therapeutic antibodies. This unique characteristic enabled the simultaneous application of CD38jd4a with therapeutic antibodies for CD38 detection on CD38-positive Ramos cells by flow cytometry without cross-interference. Importantly, clinical blood sample analysis revealed that CD38jd4a was capable of effectively detecting CD38 despite epitope masking, thereby overcoming limitations of conventional antibody-based detection methods. Given the small molecular size and excellent performance, CD38jd4a is expected to be a robust diagnostic tool for CD38 detection, offering a promising alternative for clinical diagnostics of CD38.
- Aptamer,
- SELEX,
- Diagnosis,
- CD38,
- Flow analysis
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