TY - JOUR
T1 - A CRISPR-based assay for the detection of opportunistic infections post-transplantation and for the monitoring of transplant rejection
AU - Kaminski, Michael M.
AU - Alcantar, Miguel A.
AU - Lape, Isadora T.
AU - Greensmith, Robert
AU - Huske, Allison C.
AU - Valeri, Jacqueline A.
AU - Marty, Francisco M.
AU - Klämbt, Verena
AU - Azzi, Jamil
AU - Akalin, Enver
AU - Riella, Leonardo V.
AU - Collins, James J.
N1 - Funding Information:
We thank R. Zaffini from viral microbiology (BWH) for helpful discussion about BKV testing and qPCR; the Crimson Core at BWH for providing samples from patients with CMV and BKV; and H. de Puig, N. Angenent-Mari, A. Dy and X. Tan for helpful discussions. M.M.K. was supported by the German Academy of Sciences, Leopoldina (LPDS 2018-01), the Clinician Scientist Program Berta–Ottenstein of the Faculty of Medicine, University of Freiburg, Germany and the Emmy Noether Programme (KA5060/1-1). M.A.A. was supported by a National Science Foundation graduate research fellowship (award no. 1122374). V.K. was supported by the DFG (grant no. 403877094). J.J.C. was supported by MIT’s Center for Microbiome Informatics and Therapeutics, the Paul G. Allen Frontiers Group and the Wyss Institute.
Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - 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.
AB - 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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U2 - 10.1038/s41551-020-0546-5
DO - 10.1038/s41551-020-0546-5
M3 - Article
C2 - 32284553
AN - SCOPUS:85083309600
SN - 2157-846X
VL - 4
SP - 601
EP - 609
JO - Nature Biomedical Engineering
JF - Nature Biomedical Engineering
IS - 6
ER -