Description:
Princeton Invention #
05-2225
Researchers at
Princeton University have developed a robust system for functional expression of
heterologous G-protein coupled receptors (GPCRs) in the yeast Saccharomyces
cerevisiae and have successfully applied this system to develop novel
biosensors based on the concepts of combinatorial recognition. Their work
has demonstrated the feasibility of modifying existing GPCR¿s to constitute an
array of sensors that in sum have recognition far in excess of the number of
detector elements. Sensors based on GPCRs organized in a combinatorial
array can provide a uniform detector design that could (1) detect at very
low concentrations tens to hundreds of thousands of analytes, (2)
recognize any of a very large collection of known analytes, (3) detect and
distinguish the presence of any new, previously unknown , analyte and add the
new analyte to its repertoire of known analytes, (4) perform detection in the
background of other, confounding analytes and (5) provide information on sources
of analytes. This invention can be used immediately in the specialty
chemicals/pharmaceutical manufacturing industries.
The invention
also holds the potential to be further developed for use in integrated devices
for monitoring chemical environments. Possible applications include air and
groundwater monitoring, biohazard detection, drug testing and instantaneous
blood chemistry monitoring. This later tool could be quite valuable in the
pharmaceutical industry for evaluating drug metabolism during discovery research
and in pharmacogenomic studies in late stage development.
Biological
assays are frequently utilized for chemical detection because of their
convenience, as well as their high degree of sensitivity and specificity
relative to alternative means of chemical analysis. Presently the vast
majority of biological assays for chemical analytes are based on monoclonal
antibodies or coupled enzyme assays. The region of chemical space immediately
addressable by the invention includes all GPCR ligands, which encompass nearly
40% of drug compounds currently on the market, and chemically related compounds,
which would likely include the synthetic precursors of many drug compounds. The
invention relies on repeated mutagenesis and selection of receptors to increase
the breadth of the chemical repertoire recognizable by GPCRs and to create
ensembles of receptors capable of discriminating among related chemicals that
could not be distinguished by a single naturally occurring receptor. The ease of
mutagenesis and selection for this chemical analysis is far greater than for
coupled enzyme assays, and the ensemble of chemicals that can be analyzed by
GPCRs encompasses an economically relevant set of compounds, many of which are
not readily addressable by alternative techniques.
This system also
is distinct from alternative chemical detection technologies in that the GPCRs
used for chemical analysis are linked to cellular signal transduction pathways
in a variety of eukaryotic cells. This affords the opportunity to design
genetically selectable chemical screens, in which the chemical analyte of
interest is capable of controlling the life or death, or other properties of a
cell. Currently, neither enzymatic assays nor antibody-based chemical assays can
be effectively linked to cellular signaling pathways in a systemic
way.
References :
Creation of GPCR-based chemical
sensors by directed evolution in yeast, Protein Engineering, Design &
Selection, Vol 10, No.1, pp.1-8, 2006
Princeton is currently seeking
industrial collaborators to further the development and commercialization of
this technology. Patent protection is pending.
For more information on Princeton
University Invention # 05-2225 please contact:
Laurie Tzodikov
Office of Technology Licensing and Intellectual Property
Princeton University
4 New South Building
Princeton, NJ 08544-0036
(609) 258-7256
(609) 258-1159 fax
tzodikov@princeton.edu