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Bioluminescent sensor proteins for point-of-care therapeutic drug monitoring

Nature Chemical Biology volume 10, pages 598–603 (2014)Cite this article

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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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Figure 1: Design and performance of a sensor for methotrexate.
Figure 2: Measuring methotrexate concentrations in patient samples using a point-and-shoot digital camera.
Figure 3: LUCID for tacrolimus and sirolimus.
Figure 4: LUCID for cyclosporin A.
Figure 5: LUCIDs for topiramate and digoxin.

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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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Authors and Affiliations

  1. École Polytechnique Fédérale de Lausanne, Institute of Chemical Sciences and Engineering, Lausanne, Switzerland

    Rudolf Griss, Alberto Schena, Luc Reymond, Luc Patiny & Kai Johnsson

  2. École Polytechnique Fédérale de Lausanne, Institute of Bioengineering, Lausanne, Switzerland

    Rudolf Griss, Alberto Schena, Luc Reymond & Kai Johnsson

  3. National Centre of Competence in Research in Chemical Biology, Lausanne, Switzerland

    Rudolf Griss, Alberto Schena, Luc Reymond & Kai Johnsson

  4. Clinical Chemistry Laboratory, Service of Biomedicine, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland

    Dominique Werner

  5. Department of Biochemistry, University of Washington, Seattle, Washington, USA

    Christine E Tinberg & David Baker

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  1. Rudolf Griss
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Contributions

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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Correspondence to Kai Johnsson.

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Competing interests

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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Supplementary Notes 1 and 2 and Supplementary Results. (PDF 4186 kb)

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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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