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

Author

Listed:
  • Mindong Liang

    (East China University of Science and Technology (ECUST)
    Anhui University)

  • Zilong Li

    (Chinese Academy of Sciences)

  • Weishan Wang

    (Chinese Academy of Sciences)

  • Jiakun Liu

    (East China University of Science and Technology (ECUST)
    Chinese Academy of Sciences)

  • Leshi Liu

    (East China University of Science and Technology (ECUST))

  • Guoliang Zhu

    (East China University of Science and Technology (ECUST))

  • Loganathan Karthik

    (East China University of Science and Technology (ECUST))

  • Man Wang

    (Shanghai Jiao Tong University)

  • Ke-Feng Wang

    (East China University of Science and Technology (ECUST))

  • Zhong Wang

    (Sixth People’s Hospital South Campus Affiliated to Shanghai Jiao Tong University)

  • Jing Yu

    (Sixth People’s Hospital South Campus Affiliated to Shanghai Jiao Tong University)

  • Yuting Shuai

    (East China University of Science and Technology (ECUST))

  • Jiaming Yu

    (East China University of Science and Technology (ECUST))

  • Lu Zhang

    (East China University of Science and Technology (ECUST))

  • Zhiheng Yang

    (East China University of Science and Technology (ECUST))

  • Chuan Li

    (East China University of Science and Technology (ECUST))

  • Qian Zhang

    (East China University of Science and Technology (ECUST))

  • Tong Shi

    (East China University of Science and Technology (ECUST))

  • Liming Zhou

    (East China University of Science and Technology (ECUST))

  • Feng Xie

    (Chinese Academy of Sciences)

  • Huanqin Dai

    (Chinese Academy of Sciences)

  • Xueting Liu

    (East China University of Science and Technology (ECUST))

  • Jingyu Zhang

    (East China University of Science and Technology (ECUST))

  • Guang Liu

    (East China University of Science and Technology (ECUST))

  • Ying Zhuo

    (East China University of Science and Technology (ECUST))

  • Buchang Zhang

    (Anhui University)

  • Chenli Liu

    (Chinese Academy of Sciences)

  • Shanshan Li

    (Chinese Academy of Agricultural Sciences)

  • Xuekui Xia

    (Qilu University of Technology (Shandong Academy of Sciences))

  • Yaojun Tong

    (Technical University of Denmark)

  • Yanwen Liu

    (inBiome Sciences)

  • Gil Alterovitz

    (Harvard Medical School Countway Library)

  • Gao-Yi Tan

    (East China University of Science and Technology (ECUST))

  • Li-Xin Zhang

    (East China University of Science and Technology (ECUST))

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 (CRISPR-Cas12a- and aTF-mediated small molecule detector). 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.

Suggested Citation

  • Mindong Liang & Zilong Li & Weishan Wang & Jiakun Liu & Leshi Liu & Guoliang Zhu & Loganathan Karthik & Man Wang & Ke-Feng Wang & Zhong Wang & Jing Yu & Yuting Shuai & Jiaming Yu & Lu Zhang & Zhiheng , 2019. "A CRISPR-Cas12a-derived biosensing platform for the highly sensitive detection of diverse small molecules," Nature Communications, Nature, vol. 10(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11648-1
    DOI: 10.1038/s41467-019-11648-1
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    Cited by:

    1. Dan Xiao & Wen Zhang & Xiaoting Guo & Yidong Liu & Chunxia Hu & Shiting Guo & Zhaoqi Kang & Xianzhi Xu & Cuiqing Ma & Chao Gao & Ping Xu, 2021. "A d-2-hydroxyglutarate biosensor based on specific transcriptional regulator DhdR," Nature Communications, Nature, vol. 12(1), pages 1-14, December.

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