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Deployable CRISPR-Cas13a diagnostic tools to detect and report Ebola and Lassa virus cases in real-time

Author

Listed:
  • Kayla G. Barnes

    (Broad Institute of MIT and Harvard
    Harvard T.H. Chan School of Public Health, Harvard University
    MRC-University of Glasgow Centre for Virus Research)

  • Anna E. Lachenauer

    (Broad Institute of MIT and Harvard
    Stanford University School of Medicine)

  • Adam Nitido

    (Ragon Institute of MGH, MIT, and Harvard
    Harvard Medical School)

  • Sameed Siddiqui

    (Broad Institute of MIT and Harvard
    Massachusetts Institute of Technology)

  • Robin Gross

    (National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Brett Beitzel

    (The United States Army Medical Research Institute for Infectious Disease)

  • Katherine J. Siddle

    (Broad Institute of MIT and Harvard
    Harvard University)

  • Catherine A. Freije

    (Broad Institute of MIT and Harvard
    Harvard Medical School)

  • Bonnie Dighero-Kemp

    (National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Samar B. Mehta

    (Broad Institute of MIT and Harvard
    Beth Israel Deaconess Medical Center)

  • Amber Carter

    (Broad Institute of MIT and Harvard)

  • Jessica Uwanibe

    (Redeemer’s University
    College of Natural Sciences, Redeemer’s University)

  • Fehintola Ajogbasile

    (Redeemer’s University
    College of Natural Sciences, Redeemer’s University)

  • Testimony Olumade

    (Redeemer’s University
    College of Natural Sciences, Redeemer’s University)

  • Ikponmwosa Odia

    (Institute of Lassa Fever Research and Control, Irrua Specialist Teaching Hospital)

  • John Demby Sandi

    (Redeemer’s University
    Kenema Government Hospital)

  • Mambu Momoh

    (Redeemer’s University
    Kenema Government Hospital)

  • Hayden C. Metsky

    (Broad Institute of MIT and Harvard
    MIT)

  • Chloe K. Boehm

    (Broad Institute of MIT and Harvard)

  • Aaron E. Lin

    (Broad Institute of MIT and Harvard
    Harvard Medical School)

  • Molly Kemball

    (Broad Institute of MIT and Harvard
    Harvard University)

  • Daniel J. Park

    (Broad Institute of MIT and Harvard)

  • Luis Branco

    (Zalgen Labs)

  • Matt Boisen

    (Zalgen Labs)

  • Brian Sullivan

    (The Scripps Research Institute)

  • Mihret F. Amare

    (Walter Reed Army Institute of Research
    Henry M. Jackson Foundation for the Advancement of Military Medicine)

  • Abdulwasiu B. Tiamiyu

    (Walter Reed Army Institute of Research
    Henry M. Jackson Foundation Medical Research International)

  • Zahra F. Parker

    (Walter Reed Army Institute of Research
    Henry M. Jackson Foundation for the Advancement of Military Medicine)

  • Michael Iroezindu

    (Walter Reed Army Institute of Research
    Henry M. Jackson Foundation Medical Research International)

  • Donald S. Grant

    (Kenema Government Hospital
    Ministry of Health and Sanitation)

  • Kayvon Modjarrad

    (Walter Reed Army Institute of Research)

  • Cameron Myhrvold

    (Broad Institute of MIT and Harvard
    Harvard University)

  • Robert F. Garry

    (Zalgen Labs
    Tulane University School of Medicine)

  • Gustavo Palacios

    (The United States Army Medical Research Institute for Infectious Disease)

  • Lisa E. Hensley

    (National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Stephen F. Schaffner

    (Broad Institute of MIT and Harvard
    Harvard T.H. Chan School of Public Health, Harvard University
    Harvard University)

  • Christian T. Happi

    (Harvard T.H. Chan School of Public Health, Harvard University
    Redeemer’s University
    College of Natural Sciences, Redeemer’s University
    Institute of Lassa Fever Research and Control, Irrua Specialist Teaching Hospital)

  • Andres Colubri

    (Broad Institute of MIT and Harvard
    Harvard University)

  • Pardis C. Sabeti

    (Broad Institute of MIT and Harvard
    Harvard T.H. Chan School of Public Health, Harvard University
    Harvard University
    Howard Hughes Medical Institute)

Abstract

Recent outbreaks of viral hemorrhagic fevers (VHFs), including Ebola virus disease (EVD) and Lassa fever (LF), highlight the urgent need for sensitive, deployable tests to diagnose these devastating human diseases. Here we develop CRISPR-Cas13a-based (SHERLOCK) diagnostics targeting Ebola virus (EBOV) and Lassa virus (LASV), with both fluorescent and lateral flow readouts. We demonstrate on laboratory and clinical samples the sensitivity of these assays and the capacity of the SHERLOCK platform to handle virus-specific diagnostic challenges. We perform safety testing to demonstrate the efficacy of our HUDSON protocol in heat-inactivating VHF viruses before SHERLOCK testing, eliminating the need for an extraction. We develop a user-friendly protocol and mobile application (HandLens) to report results, facilitating SHERLOCK’s use in endemic regions. Finally, we successfully deploy our tests in Sierra Leone and Nigeria in response to recent outbreaks.

Suggested Citation

  • Kayla G. Barnes & Anna E. Lachenauer & Adam Nitido & Sameed Siddiqui & Robin Gross & Brett Beitzel & Katherine J. Siddle & Catherine A. Freije & Bonnie Dighero-Kemp & Samar B. Mehta & Amber Carter & J, 2020. "Deployable CRISPR-Cas13a diagnostic tools to detect and report Ebola and Lassa virus cases in real-time," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17994-9
    DOI: 10.1038/s41467-020-17994-9
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