Title:
DIRECTED EVOLUTION BIOSENSORS
Document Type and Number:
WIPO Patent Application WO1999051777
Kind Code:
A3
Abstract:
The invention exploits the evolutionary principles responsible for the development of the broad spectrum general odorant detector system, to crate a G-protein coupled receptor (GPCR) based system capable of detecting and discriminating between thousands of chemicals. The means is to subject a defined set of receptors such as G-protein coupled receptors, tyrosine kinase receptors, and/or ion channels, to the types of evolutionary forces that have created the array of approximately 1,000 natural receptors used in general olfaction by higher animals. This goal is accompolished by "directed evolution-in-a-test-tube" by imposing very high rates of mutation and extremely strict selection criteria to create a sensor. The novel sensor is selected using a sensitive melanophore-based functional bioassay. Stimulation of the sensor upon interaction with chemical signatures derived from ordinances will result in a calcium ion flux rapidly detectable as a fluorescent signal.
Inventors:
LERNER MICHAEL R (US)
Application Number:
PCT/US1999/007566
Publication Date:
December 09, 1999
Filing Date:
April 06, 1999
Export Citation:
Assignee:
BUNSEN RUSH LAB INC (US)
LERNER MICHAEL R (US)
LERNER MICHAEL R (US)
International Classes:
G01N33/50; C12N15/09; C12N15/10; C12Q1/02; C12Q1/68; C12Q1/6811; G01N33/15; G01N33/566; G01N33/68; G01N33/74; (IPC1-7): G01N33/566; G01N33/50
Domestic Patent References:
| WO1995002823A1 | 1995-01-26 | |||
| WO1993023431A1 | 1993-11-25 | |||
| WO1997042490A1 | 1997-11-13 | |||
| WO1999019506A2 | 1999-04-22 |
Foreign References:
| US5462856A | 1995-10-31 |
Other References:
T.S. MCCLINTOCK ET AL.: "Functional analysis by imaging of melanophore pigment dispersion of chimeric receptors constructed by recombinant polymerase chain reaction", BRAIN RESEARCH (ISSN: 1385-299X), vol. 2, no. 1, 1 December 1997 (1997-12-01), nl, pages 59 - 68, XP002112945
LERNER M.R.: "Tools for investigating functional interactions between ligands and G-protein-coupled receptors", TRENDS IN NEUROSCIENCES, vol. 17, no. 4, 1994, ISSN: 0166-2236, pages 142 - 146, XP002113036
ZICCARDI M. ET AL.: "Direct detection of dioxins and related chemicals in small quantities of human serum using a recombinant cel bioassay", ORGANOHALOGEN COMPOUNDS, vol. 31, 1997, ISSN: 1026-4892, pages 215 - 218, XP002112946
KRYSTEK S.R. ET AL.: "Mutation of peptide binding site in transmembrane region of a G protein -Coupled receptor accounts for endothelin receptor subtype selectivity", JOURN. BIOLOGICAL CHEMISTRY, vol. 269, no. 17, 1994, US (ISSN: 0021-9258), pages 12383 - 12386, XP002112947
LERNER M.R.: "Tools for investigating functional interactions between ligands and G-protein-coupled receptors", TRENDS IN NEUROSCIENCES, vol. 17, no. 4, 1994, ISSN: 0166-2236, pages 142 - 146, XP002113036
ZICCARDI M. ET AL.: "Direct detection of dioxins and related chemicals in small quantities of human serum using a recombinant cel bioassay", ORGANOHALOGEN COMPOUNDS, vol. 31, 1997, ISSN: 1026-4892, pages 215 - 218, XP002112946
KRYSTEK S.R. ET AL.: "Mutation of peptide binding site in transmembrane region of a G protein -Coupled receptor accounts for endothelin receptor subtype selectivity", JOURN. BIOLOGICAL CHEMISTRY, vol. 269, no. 17, 1994, US (ISSN: 0021-9258), pages 12383 - 12386, XP002112947
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