Development and Characterization of Recombinase-Based Isothermal Amplification Assays (RPA/RAA) for the Rapid Detection of Monkeypox Virus

Viruses. 2022 Sep 23;14(10):2112. doi: 10.3390/v14102112.

Abstract

Monkeypox is a zoonotic disease caused by monkeypox virus (MPXV), in which outbreaks mainly occurred in West and Central Africa, with only sporadic spillovers to countries outside Africa due to international travel or close contact with wildlife. During May 2022, multiple countries in Europe, North and South America, Australia, Asia, and Africa reported near-simultaneous outbreaks of MPXV, the first time that patient clusters were reported over such a large geographical area. Cases have no known epidemiological links to MPXV-endemic countries in West or Central Africa. Real-time PCR is currently the gold standard for MPXV diagnostics, but it requires trained laboratory personnel and specialized equipment, and results can only be obtained after several hours. A rapid and simple-to-operate point-of-care diagnostic test for MPXV is crucial for limiting its spread and controlling outbreaks. Here, three recombinase-based isothermal amplification assays (RPA/RAA) for the rapid detection of MPXV isolates were developed. These three assays target the MPXV G2R gene, and the limit of detection for these systems is approximately 100 copies of DNA per reaction. The assays were found to be specific and non-cross reactive against other pox viruses, such as vaccinia virus, and the results can be visualized within 20-30 min. The assays were validated with DNA extracted from 19 clinical samples from suspected or confirmed MPXV patients from Central Africa, and found to be consistent with findings from traditional qPCR. These results provide a solid platform for the early diagnosis of potential MPXV cases, and will help with the control and prevention of current and future outbreaks.

Keywords: CRISPR-Cas12a; lateral flow; monkeypox virus; nucleic acid detection; rapid detection system; recombinase polymerase amplification assay.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Europe
  • Humans
  • Monkeypox virus* / genetics
  • Mpox (monkeypox)* / diagnosis
  • Mpox (monkeypox)* / epidemiology
  • Nucleic Acid Amplification Techniques / methods
  • Real-Time Polymerase Chain Reaction
  • Recombinases
  • Sensitivity and Specificity

Substances

  • Recombinases

Grants and funding

This project was supported by the Ministry of Science and Technology of China (Grant No. 2021YFC0863400, 2022YFE0114700), the Alliance of International Scientific Organizations (Grant No. ANSO-CR-SP-2020-02), the Shanghai Municipal Science and Technology Major Project (Grant No. 2019SHZDZX02), G4 funding from Institut Pasteur, Fondation Merieux and Chinese Academy of Sciences to G.W., and the International Affairs Department of the Institut Pasteur of Paris. This project was also supported by Agence National de la Recherche (Grant AFRIPOX). The funders had no role in study design, data analysis, or preparation of the manuscript.