Abstract
For many drugs, finding the balance between efficacy and toxicity requires monitoring their concentrations in the patient's blood. Quantifying drug levels at the bedside or at home would have advantages in terms of therapeutic outcome and convenience, but current techniques require the setting of a diagnostic laboratory. We have developed semisynthetic bioluminescent sensors that permit precise measurements of drug concentrations in patient samples by spotting minimal volumes on paper and recording the signal using a simple point-and-shoot camera. Our sensors have a modular design consisting of a protein-based and a synthetic part and can be engineered to selectively recognize a wide range of drugs, including immunosuppressants, antiepileptics, anticancer agents and antiarrhythmics. This low-cost point-of-care method could make therapies safer, increase the convenience of doctors and patients and make therapeutic drug monitoring available in regions with poor infrastructure.
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Acknowledgements
This work was supported by École Polytechnique Fédérale de Lausanne, the Swiss National Science Foundation, the National Centre of Competence in Research Chemical Biology, and the Defense Threat Reduction Agency. We are grateful to T. Buclin, N. Widmer and L. Decosterd from the CHUV for helpful discussions.
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R.G., A.S. and K.J. designed experiments, R.G. and A.S. performed experiments, A.S. and L.R. performed chemical synthesis and characterization of the sensor ligands, L.P. wrote software for image analysis, D.W. provided patient samples, and C.E.T. and D.B. provided DIG10.3. All of the authors contributed to the writing of the manuscript.
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R.G., A.S. and K.J. have filed a Patent Cooperation Treaty (World Intellectual Property Organization) patent application on the design and use of LUCIDs.
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Griss, R., Schena, A., Reymond, L. et al. Bioluminescent sensor proteins for point-of-care therapeutic drug monitoring. Nat Chem Biol 10, 598–603 (2014). https://doi.org/10.1038/nchembio.1554
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DOI: https://doi.org/10.1038/nchembio.1554
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