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NAPTUNE: nucleic acids and protein biomarkers testing via ultra-sensitive nucleases escalation

Author

Listed:
  • Tao Hu

    (Zhejiang University School of Medicine
    National University of Singapore
    Hangzhou Medical College)

  • Xinxin Ke

    (Zhejiang University School of Medicine)

  • Yingying Yu

    (Zhejiang University School of Medicine)

  • Hongmei Feng

    (Zhejiang University School of Medicine
    Hangzhou Medical College)

  • Senfeng Zhang

    (National University of Singapore)

  • Yinuo Cui

    (National University of Singapore)

  • Boyang Zhang

    (National University of Singapore)

  • Min He

    (Zhejiang University School of Medicine)

  • Yinbing Tang

    (Zhejiang University School of Medicine)

  • Lei Liu

    (Zhejiang University School of Medicine)

  • Yu Lin

    (Shanghai Jiao Tong University)

  • Quanquan Ji

    (National University of Singapore)

  • Chuanxia Chen

    (School of Materials Science and Engineering University of Jinan)

  • Chunlong Xu

    (Lingang Laboratory)

  • Chunyi Hu

    (National University of Singapore
    National University of Singapore
    National University of Singapore)

Abstract

In an era where swift and precise diagnostic capabilities are paramount, we introduce NAPTUNE (Nucleic acids and Protein Biomarkers Testing via Ultra-sensitive Nucleases Escalation), an innovative platform for the amplification-free detection of nucleic acids and protein biomarkers in less than 45 minutes. Using a tandem cascade of endonucleases, NAPTUNE employs apurinic/apyrimidinic endonuclease 1 (APE1) to generate DNA guides, enabling the detection of target nucleic acids at femtomolar levels. The sensitivity is elevated to attomolar levels through the action of Pyrococcus furiosus Argonaute (PfAgo), which intensifies probe cleavage, thereby boosting both sensitivity and specificity within an innovative in-situ cascade circuit. This technology not only streamlines rapid, onsite diagnostics without pre-amplification but also demonstrates exceptional accuracy in identifying a broad spectrum of nucleic acids and crucial cancer-related protein biomarkers directly from clinical samples. The development of a portable device for point-of-care testing further underscores NAPTUNE’s potential to transform diagnostic processes, especially in resource-limited environments, marking a significant diversity forward in medical diagnostics and patient care.

Suggested Citation

  • Tao Hu & Xinxin Ke & Yingying Yu & Hongmei Feng & Senfeng Zhang & Yinuo Cui & Boyang Zhang & Min He & Yinbing Tang & Lei Liu & Yu Lin & Quanquan Ji & Chuanxia Chen & Chunlong Xu & Chunyi Hu, 2025. "NAPTUNE: nucleic acids and protein biomarkers testing via ultra-sensitive nucleases escalation," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56653-9
    DOI: 10.1038/s41467-025-56653-9
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    References listed on IDEAS

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    1. Lidiya Lisitskaya & Alexei A. Aravin & Andrey Kulbachinskiy, 2018. "DNA interference and beyond: structure and functions of prokaryotic Argonaute proteins," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    2. Margot Karlikow & Evan Amalfitano & Xiaolong Yang & Jennifer Doucet & Abigail Chapman & Peivand Sadat Mousavi & Paige Homme & Polina Sutyrina & Winston Chan & Sofia Lemak & Alexander F. Yakunin & Adam, 2023. "CRISPR-induced DNA reorganization for multiplexed nucleic acid detection," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    3. Hyowon Jang & Jayeon Song & Sunjoo Kim & Jung-Hyun Byun & Kyoung G. Lee & Kwang-Hyun Park & Euijeon Woo & Eun-Kyung Lim & Juyeon Jung & Taejoon Kang, 2023. "ANCA: artificial nucleic acid circuit with argonaute protein for one-step isothermal detection of antibiotic-resistant bacteria," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    4. Guanhua Xun & Stephan Thomas Lane & Vassily Andrew Petrov & Brandon Elliott Pepa & Huimin Zhao, 2021. "A rapid, accurate, scalable, and portable testing system for COVID-19 diagnosis," Nature Communications, Nature, vol. 12(1), pages 1-9, December.
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