Mass-encoded synthetic biomarkers for multiplexed urinary monitoring of disease
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Bhatia_Mass-encoded.pdf
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Author(s)
von Maltzahn, Geoffrey
Murugappan, Gayathree
Mo, Steven
Sverdlov, Deanna Y
Liu, Susan B
Popov, Yury
Schuppan, Detlef
Kwong, Gabriel A.
Warren, Andrew D.
Papayannopoulos, Ioannis A.
Date Issued
December 2012
Journal
Nature Biotechnology
Publisher
Nature Publishing Group
Citation
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.
Version
Author's final manuscript
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Koch Institute for Integrative Cancer Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1038/nbt.2464
