Mass-encoded synthetic biomarkers for multiplexed urinary monitoring of disease
Author(s)von Maltzahn, Geoffrey; Murugappan, Gayathree; Abudayyeh, Omar; Mo, Steven; Sverdlov, Deanna Y; Liu, Susan B; Popov, Yury; Schuppan, Detlef; Kwong, Gabriel A.; Warren, Andrew D.; Bhatia, Sangeeta N.; Papayannopoulos, Ioannis A.; von Maltzhan, Geoffrey; ... Show more Show less
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Biomarkers are becoming increasingly important in the clinical management of complex diseases, yet our ability to discover new biomarkers remains limited by our dependence on endogenous molecules. Here we describe the development of exogenously administered 'synthetic biomarkers' composed of mass-encoded peptides conjugated to nanoparticles that leverage intrinsic features of human disease and physiology for noninvasive urinary monitoring. These protease-sensitive agents perform three functions in vivo: they target sites of disease, sample dysregulated protease activities and emit mass-encoded reporters into host urine for multiplexed detection by mass spectrometry. Using mouse models of liver fibrosis and cancer, we show that these agents can noninvasively monitor liver fibrosis and resolution without the need for invasive core biopsies and substantially improve early detection of cancer compared with current clinically used blood biomarkers. This approach of engineering synthetic biomarkers for multiplexed urinary monitoring should be broadly amenable to additional pathophysiological processes and point-of-care diagnostics.
DepartmentInstitute for Medical Engineering and Science; David H. Koch Institute for Integrative Cancer Research at MIT; Harvard University--MIT Division of Health Sciences and Technology; Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Nature Publishing Group
Kwong, Gabriel A, Geoffrey von Maltzahn, Gayathree Murugappan, Omar Abudayyeh, Steven Mo, Ioannis A Papayannopoulos, Deanna Y Sverdlov, et al. “Mass-Encoded Synthetic Biomarkers for Multiplexed Urinary Monitoring of Disease.” Nature Biotechnology 31, no. 1 (December 16, 2012): 63–70.
Author's final manuscript