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A CRISPR-enhanced metagenomic NGS test to improve pandemic preparedness

The lack of preparedness for detecting and responding to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogen (i.e., COVID-19) has caused enormous harm to public health and the economy. Testing strategies deployed on a population scale at day zero, i.e., the time of the first re...

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Detalles Bibliográficos
Autores principales: Chan, Agnes P., Siddique, Azeem, Desplat, Yvain, Choi, Yongwook, Ranganathan, Sridhar, Choudhary, Kumari Sonal, Khalid, M. Faizan, Diaz, Josh, Bezney, Jon, DeAscanis, Dante, George, Zenas, Wong, Shukmei, Selleck, William, Bowers, Jolene, Zismann, Victoria, Reining, Lauren, Highlander, Sarah, Brown, Keith, Armstrong, Jon R., Hakak, Yaron, Schork, Nicholas J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10110940/
https://www.ncbi.nlm.nih.gov/pubmed/37323571
http://dx.doi.org/10.1016/j.crmeth.2023.100463
Descripción
Sumario:The lack of preparedness for detecting and responding to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogen (i.e., COVID-19) has caused enormous harm to public health and the economy. Testing strategies deployed on a population scale at day zero, i.e., the time of the first reported case, would be of significant value. Next-generation sequencing (NGS) has such capabilities; however, it has limited detection sensitivity for low-copy-number pathogens. Here, we leverage the CRISPR-Cas9 system to effectively remove abundant sequences not contributing to pathogen detection and show that NGS detection sensitivity of SARS-CoV-2 approaches that of RT-qPCR. The resulting sequence data can also be used for variant strain typing, co-infection detection, and individual human host response assessment, all in a single molecular and analysis workflow. This NGS work flow is pathogen agnostic and, therefore, has the potential to transform how large-scale pandemic response and focused clinical infectious disease testing are pursued in the future.