Institute for Medical Engineering and Science and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
Nat Biomed Eng. 2020 Jun;4(6):601-609. doi: 10.1038/s41551-020-0546-5. Epub 2020 Apr 13.
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.
在器官移植中,感染和排斥是导致移植物丧失的主要原因。它们通过免疫抑制的净状态联系在一起。为了更早地诊断和治疗这些疾病,并改善长期患者预后,需要制定更精细的移植物移植后患者监测策略。在这里,我们展示了一种快速且廉价的基于 CRISPR-Cas13 的检测方法,该方法可以准确检测来自患者血液和尿液样本的 BK 多瘤病毒 DNA 和巨细胞病毒 DNA,以及来自发生急性肾移植排斥反应的患者尿液样本中 CXCL9 信使 RNA(移植物排斥的标志物)水平升高。我们对该检测方法进行了侧向流动读取的适配,通过简单的可视化实现了常见机会性病毒感染和移植物排斥的移植后监测,并且应该有助于移植后的即时护理监测。