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Mirror-Image L-DNA Aptamers Enable Stable In Vivo Dopamine Sensing

delete2026-02-06
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PRE
AI
Y
Yinghuan Liu
Y
Ying Jin
F
Fenghui Zhu
X
X. Li
C
Chunran Ma
Z
Zhining Sun
Y
Yichun Yao
K
Kaixin Song
L
Lanqun Mao
Y
Ying Jiang *
DOI:10.1021/jacs.5c22265delete
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Abstract

Abstract

En 中文
Long-term in vivo neurochemical sensing with aptamer-based electrochemical sensors is fundamentally limited by the enzymatic degradation of natural D-DNA aptamers and the instability of surface-confined sensing interfaces. Here, we generate a mirror-image L-DNA analogue of a dopamine-binding aptamer and show that chiral inversion preserves folding, affinity, and selectivity, as confirmed by circular dichroism, fluorescence binding assays, and molecular docking. Integration of this L-aptamer with a stabilized electrochemical conjugation on carbon–fiber microelectrodes yields a highly stable mirror-image molecular–electrical interface capable of sensitively transducing dopamine binding into quantitative electrochemical signals. Owing to its exceptional nuclease resistance, the L-aptamer sensor enables continuous dopamine monitoring in vivo for over 24 h─an order-of-magnitude improvement in signal over conventional D-aptamer sensors. Applied in Parkinson’s disease mouse model, the sensor resolves pathological dopamine clearance defects. These results establish mirror-image nucleic acids, when coupled with engineered electrochemical interfaces, as effective components for durable bioelectronic sensing in vivo.
Keywords:
L-DNA aptamer
dopamine sensing
in vivo monitoring
electrochemical sensors
nuclease resistance

Journal

Journal of the American Chemical Society cover
Journal of the American Chemical Society
IF:
15.6
Papers:
20.0W
Citations:
60.2W

Organization

B
beijing normal university
Scholars:
4.4K
Papers: 1.8K
Citations: 0