Key result
Novel ASA-Exo III-DW-LDA method correlates strongly with 14C labeling, identifying kaempferol as a URAT1 inhibitor.
Why the study?
The lack of a cell-based screening method limits urate-lowering drug development.
Effect estimate: r = 0.9880 for lesinurad
A novel, non-radioactive aptamer sensor array method enables ultrasensitive detection of uric acid and effective screening of urate-lowering drugs.
May facilitate non-radioactive URAT1 inhibitor screening; leaves open kaempferol efficacy in humans.
The lack of a cell-based screening method limits urate-lowering drug development. A novel method combining aptamer sensor array (ASA), exonuclease III (Exo III)- powered 3D DNA walker (DW), and linear discriminant analysis (LDA) was developed for detecting uric acid (UA) in cell lysates, referred to as ASA–Exo III-DW–LDA. Three aptamers (Apts) with different affinities for UA and its structurally similar compound, xanthine (Xan), were used to design the ASA. The combination of ASA and Exo III-DW enabled the detection of UA at the picomolar level, whereas LDA was employed to differentiate UA signals from the mixed signals of UA and Xan. Significantly, Pearson correlation analysis revealed a strong correlation between our method and the 14 C radioactive labeling method for urate anion exchanger 1 (URAT1) inhibitors, with r = 0.9880 for lesinurad and r = 0.9777 for benzbromarone. Using our method, kaempferol was identified as a promising hit compound for inhibiting the URAT1, because of its low half-maximal inhibitory concentration (IC 50 ) (18.96 μM) low toxicity in mouse renal tubular epithelial cells (mTECs), and significant urate-lowering effect in hyperuricemic mice at 5 mg/kg. Overall, this method is sensitive, cost-effective and safe, offering a novel strategy for routine urate-lowering drug screening in standard laboratories. • Developed an Exonuclease III-powered DNA Walker fluorescence sensor combined with a hURAT1 cell-based approach for urate-lowering drug screening. • The approach achieves ultrasensitive detection of uric acid at the picomolar level. • The aptamer sensor array, in conjunction with linear discriminant analysis, was employed to specifically and accurately quantify uric acid in the presence of xanthine. • The reagents were non-radioactive, making the method suitable for routine use in standard laboratory settings.
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Zheng et al. (2025) studied Hyperuricemia. ASA-Exo III-DW-LDA method vs. 14C radioactive labeling method was evaluated on Correlation with 14C radioactive labeling method for URAT1 inhibitors (r = 0.9880 for lesinurad). A novel ASA-Exo III-DW-LDA method strongly correlated with the 14C radioactive labeling method (r=0.9880 for lesinurad) and identified kaempferol as a promising URAT1 inhibitor.
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