A CRISPR-based assay for the detection of opportunistic infections post-transplantation and for the monitoring of transplant rejection

Michael M. Kaminski; Miguel A. Alcantar; Isadora T. Lape; Robert Greensmith; Allison C. Huske; Jacqueline A. Valeri; Francisco M. Marty; Verena Klämbt; Jamil Azzi; Enver Akalin; Leonardo V. Riella; James J. Collins

doi:10.1038/s41551-020-0546-5

A CRISPR-based assay for the detection of opportunistic infections post-transplantation and for the monitoring of transplant rejection

Michael M. Kaminski, Miguel A. Alcantar, Isadora T. Lape, Robert Greensmith, Allison C. Huske, Jacqueline A. Valeri, Francisco M. Marty, Verena Klämbt, Jamil Azzi, Enver Akalin, Leonardo V. Riella, James J. Collins

Medicine

Research output: Contribution to journal › Article › peer-review

76 Scopus citations

Abstract

In organ transplantation, infection and rejection are major causes of graft loss. They are linked by the net state of immunosuppression. To diagnose and treat these conditions earlier, and to improve long-term patient outcomes, refined strategies for the monitoring of patients after graft transplantation are needed. Here, we show that a fast and inexpensive assay based on CRISPR–Cas13 accurately detects BK polyomavirus DNA and cytomegalovirus DNA from patient-derived blood and urine samples, as well as CXCL9 messenger RNA (a marker of graft rejection) at elevated levels in urine samples from patients experiencing acute kidney transplant rejection. The assay, which we adapted for lateral-flow readout, enables—via simple visualization—the post-transplantation monitoring of common opportunistic viral infections and of graft rejection, and should facilitate point-of-care post-transplantation monitoring.

Original language	English (US)
Pages (from-to)	601-609
Number of pages	9
Journal	Nature Biomedical Engineering
Volume	4
Issue number	6
DOIs	https://doi.org/10.1038/s41551-020-0546-5
State	Published - Jun 1 2020

ASJC Scopus subject areas

Biotechnology
Bioengineering
Medicine (miscellaneous)
Biomedical Engineering
Computer Science Applications

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Kaminski, M. M., Alcantar, M. A., Lape, I. T., Greensmith, R., Huske, A. C., Valeri, J. A., Marty, F. M., Klämbt, V., Azzi, J., Akalin, E., Riella, L. V., & Collins, J. J. (2020). A CRISPR-based assay for the detection of opportunistic infections post-transplantation and for the monitoring of transplant rejection. Nature Biomedical Engineering, 4(6), 601-609. https://doi.org/10.1038/s41551-020-0546-5

Kaminski, MM, Alcantar, MA, Lape, IT, Greensmith, R, Huske, AC, Valeri, JA, Marty, FM, Klämbt, V, Azzi, J, Akalin, E, Riella, LV & Collins, JJ 2020, 'A CRISPR-based assay for the detection of opportunistic infections post-transplantation and for the monitoring of transplant rejection', Nature Biomedical Engineering, vol. 4, no. 6, pp. 601-609. https://doi.org/10.1038/s41551-020-0546-5

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abstract = "In organ transplantation, infection and rejection are major causes of graft loss. They are linked by the net state of immunosuppression. To diagnose and treat these conditions earlier, and to improve long-term patient outcomes, refined strategies for the monitoring of patients after graft transplantation are needed. Here, we show that a fast and inexpensive assay based on CRISPR–Cas13 accurately detects BK polyomavirus DNA and cytomegalovirus DNA from patient-derived blood and urine samples, as well as CXCL9 messenger RNA (a marker of graft rejection) at elevated levels in urine samples from patients experiencing acute kidney transplant rejection. The assay, which we adapted for lateral-flow readout, enables—via simple visualization—the post-transplantation monitoring of common opportunistic viral infections and of graft rejection, and should facilitate point-of-care post-transplantation monitoring.",

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A CRISPR-based assay for the detection of opportunistic infections post-transplantation and for the monitoring of transplant rejection

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