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

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 transplant...

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Main Authors: Kaminski, Michael M., Alcantar, Miguel A., Lape, Isadora T., Greensmith, Robert, Huske, Allison C., Valeri, Jacqueline A., Marty, Francisco M., Klämbt, Verena, Azzi, Jamil, Akalin, Enver, Riella, Leonardo V., Collins, James J.
Other Authors: Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Format: Article
Language:English
Published: Springer Science and Business Media LLC 2020
Online Access:https://hdl.handle.net/1721.1/125918
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author Kaminski, Michael M.
Alcantar, Miguel A.
Lape, Isadora T.
Greensmith, Robert
Huske, Allison C.
Valeri, Jacqueline A.
Marty, Francisco M.
Klämbt, Verena
Azzi, Jamil
Akalin, Enver
Riella, Leonardo V.
Collins, James J.
author2 Massachusetts Institute of Technology. Institute for Medical Engineering & Science
author_facet Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Kaminski, Michael M.
Alcantar, Miguel A.
Lape, Isadora T.
Greensmith, Robert
Huske, Allison C.
Valeri, Jacqueline A.
Marty, Francisco M.
Klämbt, Verena
Azzi, Jamil
Akalin, Enver
Riella, Leonardo V.
Collins, James J.
author_sort Kaminski, Michael M.
collection MIT
description 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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spelling mit-1721.1/1259182022-10-02T02:09:27Z A CRISPR-based assay for the detection of opportunistic infections post-transplantation and for the monitoring of transplant rejection Kaminski, Michael M. Alcantar, Miguel A. Lape, Isadora T. Greensmith, Robert Huske, Allison C. Valeri, Jacqueline A. Marty, Francisco M. Klämbt, Verena Azzi, Jamil Akalin, Enver Riella, Leonardo V. Collins, James J. Massachusetts Institute of Technology. Institute for Medical Engineering & Science Broad Institute of MIT and Harvard 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. National Science Foundation (Award 1122374) 2020-06-22T18:43:04Z 2020-06-22T18:43:04Z 2020-04 2019-10 2020-06-22T14:14:22Z Article http://purl.org/eprint/type/JournalArticle 2157-846X https://hdl.handle.net/1721.1/125918 Kaminski, Michael M. et al. "A CRISPR-based assay for the detection of opportunistic infections post-transplantation and for the monitoring of transplant rejection." Nature Biomedical Engineering 4, 6 (April 2020): 601–609 © 2020 The Author(s) en http://dx.doi.org/10.1038/s41551-020-0546-5 Nature Biomedical Engineering Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Springer Science and Business Media LLC Prof. Collins via Howard Silver
spellingShingle Kaminski, Michael M.
Alcantar, Miguel A.
Lape, Isadora T.
Greensmith, Robert
Huske, Allison C.
Valeri, Jacqueline A.
Marty, Francisco M.
Klämbt, Verena
Azzi, Jamil
Akalin, Enver
Riella, Leonardo V.
Collins, James J.
A CRISPR-based assay for the detection of opportunistic infections post-transplantation and for the monitoring of transplant rejection
title A CRISPR-based assay for the detection of opportunistic infections post-transplantation and for the monitoring of transplant rejection
title_full A CRISPR-based assay for the detection of opportunistic infections post-transplantation and for the monitoring of transplant rejection
title_fullStr A CRISPR-based assay for the detection of opportunistic infections post-transplantation and for the monitoring of transplant rejection
title_full_unstemmed A CRISPR-based assay for the detection of opportunistic infections post-transplantation and for the monitoring of transplant rejection
title_short A CRISPR-based assay for the detection of opportunistic infections post-transplantation and for the monitoring of transplant rejection
title_sort crispr based assay for the detection of opportunistic infections post transplantation and for the monitoring of transplant rejection
url https://hdl.handle.net/1721.1/125918
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