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Herein, we developed a CRISPR\/Cas13a-mediated photoelectrochemical (PEC) biosensing platform for direct and sensitive detection of miRNA-21. The direct and specific recognition of target miRNA-21 by crRNA-21 eliminates the need for pre-amplification and reverse transcription of miRNA-21, thereby preventing signal distortion and enhancing the sensitivity and precision of target detection. When crRNA-21 binds to miRNA-21, it activates the trans-cleavage activity of CRISPR\/Cas13a, leading to the non-specific cleavage of biotin-modified DNA with uracil bases (biotin-rU-DNA). This cleavage prevents the biotin-rU-DNA from being immobilized on the electrode surface. As a result, streptavidin cannot attach to the electrode via specific biotin binding, reducing spatial resistance and causing a positively correlated increase in the photocurrent response. This Cas-PEC biosensor has good analytical capabilities, linear responses between 10 fM and 10 nM, a minimum detection limit of 9 fM, and an excellent recovery rate in the analysis of real human serum samples. This work presented an innovative solution for detecting other biomarkers in bioanalysis and clinical diagnostics.<\/jats:p>","DOI":"10.3390\/s24186138","type":"journal-article","created":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T08:56:06Z","timestamp":1727168166000},"page":"6138","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A Photoelectrochemical Biosensor Mediated by CRISPR\/Cas13a for Direct and Specific Detection of MiRNA-21"],"prefix":"10.3390","volume":"24","author":[{"given":"Yang","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022, China"}]},{"given":"Pei","family":"Miao","sequence":"additional","affiliation":[{"name":"School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022, China"}]},{"given":"Jingyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022, China"}]},{"given":"Yan","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022, China"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022, China"}]},{"given":"Bin","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022, China"}]},{"given":"Mei","family":"Yan","sequence":"additional","affiliation":[{"name":"School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022, China"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5451","DOI":"10.1002\/jcp.27486","article-title":"An overview of microRNAs: Biology, functions, therapeutics, and analysis methods","volume":"234","author":"Saliminejad","year":"2018","journal-title":"J. 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