Liposome-mediated detection of SARS-CoV-2 RNA-positive extracellular vesicles in plasma

Bo Ning, Zhen Huang, Brady M. Youngquist, John W. Scott, Alex Niu, Christine M. Bojanowski, Kevin J. Zwezdaryk, Nakhle S. Saba, Jia Fan, Xiao Ming Yin, Jing Cao, Christopher J. Lyon, Chen zhong Li, Chad J. Roy, Tony Y. Hu

Research output: Contribution to journalArticlepeer-review

79 Scopus citations


Plasma SARS-CoV-2 RNA may represent a viable diagnostic alternative to respiratory RNA levels, which rapidly decline after infection. Quantitative PCR with reverse transcription (RT–qPCR) reference assays exhibit poor performance with plasma, probably reflecting the dilution and degradation of viral RNA released into the circulation, but these issues could be addressed by analysing viral RNA packaged into extracellular vesicles. Here we describe an assay approach in which extracellular vesicles directly captured from plasma are fused with reagent-loaded liposomes to sensitively amplify and detect a SARS-CoV-2 gene target. This approach accurately identified patients with COVID-19, including challenging cases missed by RT–qPCR. SARS-CoV-2-positive extracellular vesicles were detected at day 1 post-infection, and plateaued from day 6 to the day 28 endpoint in a non-human primate model, while signal durations for 20–60 days were observed in young children. This nanotechnology approach uses a non-infectious sample and extends virus detection windows, offering a tool to support COVID-19 diagnosis in patients without SARS-CoV-2 RNA detectable in the respiratory tract.

Original languageEnglish (US)
Pages (from-to)1039-1044
Number of pages6
JournalNature Nanotechnology
Issue number9
StatePublished - Sep 2021

ASJC Scopus subject areas

  • Bioengineering
  • Atomic and Molecular Physics, and Optics
  • Biomedical Engineering
  • General Materials Science
  • Condensed Matter Physics
  • Electrical and Electronic Engineering


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