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A CRISPR-Cas12a-derived biosensing platform for the highly sensitive detection of diverse small molecules

Open access
Liang, Mindong, Li, Zilong, Wang, Weishan, Liu, Jiakun, Liu, Leshi, Zhu, Guoliang, Karthik, Loganathan, Wang, Man, Wang, Ke-Feng, Wang, Zhong, Yu, Jing, Shuai, Yuting, Yu, Jiaming, Zhang, Lu, Yang, Zhiheng, Li, Chuan, Zhang, Qian, Shi, Tong, Zhou, Liming, Xie, Feng, Dai, Huanqin, Liu, Xueting, Zhang, Jingyu, Liu, Guang, Zhuo, Ying, Zhang, Buchang, Liu, Chenli, Li, Shanshan, Xia, Xuekui, Tong, Yaojun, Liu, Yanwen, Alterovitz, Gil, Tan, Gao-Yi, Zhang, Li-Xin·2019·Nature Communications

Abstract

Besides genome editing, CRISPR-Cas12a has recently been used for DNA detection applications with attomolar sensitivity but, to our knowledge, it has not been used for the detection of small molecules. Bacterial allosteric transcription factors (aTFs) have evolved to sense and respond sensitively to a variety of small molecules to benefit bacterial survival. By combining the single-stranded DNA cleavage ability of CRISPR-Cas12a and the competitive binding activities of aTFs for small molecules and double-stranded DNA, here we develop a simple, supersensitive, fast and high-throughput platform for the detection of small molecules, designated CaT-SMelor (C RISPR-Cas12a- and aT F-mediated s mall m ol e cu l e detect or). CaT-SMelor is successfully evaluated by detecting nanomolar levels of various small molecules, including uric acid and p-hydroxybenzoic acid among their structurally similar analogues. We also demonstrate that our CaT-SMelor directly measured the uric acid concentration in clinical human blood samples, indicating a great potential of CaT-SMelor in the detection of small molecules.

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Metadata

Authors
Liang, M., Li, Z., Wang, W., Liu, J., Liu, L., Zhu, G., Karthik, L., Wang, M., Wang, K.-F., Wang, Z., Yu, J., Shuai, Y., Yu, J., Zhang, L., Yang, Z., Li, C., Zhang, Q., Shi, T., Zhou, L., Xie, F., Dai, H., Liu, X., Zhang, J., Liu, G., Zhuo, Y., Zhang, B., Liu, C., Li, S., Xia, X., Tong, Y., Liu, Y., Alterovitz, G., Tan, G.-Y., & Zhang, L.-X.
Venue
Nature Communications
Published
2019-08-14
Volume
10
Issue
1
Pages
3672-3672
ISSN
2041-1723 (ISSN-L)
OpenAlex
W2967373993
Cited by
430
References
4
FWCI
13.89
Type
journal article
Language
en
Open access
gold

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Liang, M., Li, Z., Wang, W., Liu, J., Liu, L., Zhu, G., Karthik, L., Wang, M., Wang, K.-F., Wang, Z., Yu, J., Shuai, Y., Yu, J., Zhang, L., Yang, Z., Li, C., Zhang, Q., Shi, T., Zhou, L., . . . Zhang, L.-X. (2019). A CRISPR-Cas12a-derived biosensing platform for the highly sensitive detection of diverse small molecules. Nature Communications. https://doi.org/10.1038/s41467-019-11648-1

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