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

Rudolf Griss; Alberto Schena; Luc Reymond; Luc Patiny; Dominique Werner; Christine E Tinberg; David Baker; Kai Johnsson

doi:10.1038/nchembio.1554

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

Nat Chem Biol. 2014 Jul;10(7):598-603. doi: 10.1038/nchembio.1554. Epub 2014 Jun 8.

Authors

Rudolf Griss¹, Alberto Schena¹, Luc Reymond¹, Luc Patiny², Dominique Werner³, Christine E Tinberg⁴, David Baker⁴, Kai Johnsson¹

Affiliations

¹ 1] École Polytechnique Fédérale de Lausanne, Institute of Chemical Sciences and Engineering, Lausanne, Switzerland. [2] École Polytechnique Fédérale de Lausanne, Institute of Bioengineering, Lausanne, Switzerland. [3] National Centre of Competence in Research in Chemical Biology, Lausanne, Switzerland.
² cole Polytechnique Fédérale de Lausanne, Institute of Chemical Sciences and Engineering, Lausanne, Switzerland.
³ Clinical Chemistry Laboratory, Service of Biomedicine, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
⁴ University of Washington, Department of Biochemistry, Seattle, Washington, USA.

PMID: 24907901
DOI: 10.1038/nchembio.1554

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Arrhythmia Agents / blood
Anticonvulsants / blood
Antineoplastic Agents / blood
Biosensing Techniques
Drug Monitoring / economics
Drug Monitoring / instrumentation
Drug Monitoring / methods*
Escherichia coli / genetics
Escherichia coli / metabolism
Gene Expression
Humans
Image Processing, Computer-Assisted
Immunosuppressive Agents / blood
Luminescent Proteins / chemistry*
Luminescent Proteins / genetics
Luminescent Proteins / metabolism
Photography
Point-of-Care Systems
Protein Engineering
Recombinant Fusion Proteins / chemistry*
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / metabolism

Substances

Anti-Arrhythmia Agents
Anticonvulsants
Antineoplastic Agents
Immunosuppressive Agents
Luminescent Proteins
Recombinant Fusion Proteins

Associated data

PubChem-Substance/177348092
PubChem-Substance/177348093
PubChem-Substance/177348094
PubChem-Substance/177348095
PubChem-Substance/177348096
PubChem-Substance/177348097
PubChem-Substance/177348098
PubChem-Substance/177348099