Patents by Inventor Roger Y. Tsien

Application number: 20140093907
Abstract: Compounds and methods for determining transmembrane potential, monitoring changes in transmembrane potential, and/or drug screening are provided. In one aspect, compounds of the invention have a structure according to the formula: E-M-A, wherein A is a fluorophore, selected from xanthenes, eoumarins, cyanines, bimanes, and difluoroboradizaindacenes, charged at physiological pH; M is a molecular wire; and E is a hydrophobic moiety, wherein A and E are capable of being involved in a photo-induced, intramolecular electron transfer that quenches the fluorescence of A in response to a voltage condition. When in use, compounds of the invention are membrane-impermeant and oriented within the cell membrane such that the charged moiety localizes at the outer leaflet of the lipid bilayer and the hydrophobic moiety and molecular wire associate with the hydrophobic portion of the lipid bilayer.
Type: Application
Filed: May 21, 2012
Issued: April 3, 2014
Assignee: The Regents of the University of California
Inventors: Evan Walker Miller, Roger Y. Tsien
Patent number: 8685372
Abstract: The present invention provides methods for guiding preservation of neurons or nerves during surgery by administering a fluorescently-labeled peptide or aptamer that specifically binds to the neurons or nerves. The invention further provides targeting molecules of fluorescently-labeled peptides or aptamers that specifically bind to neurons or nerves and for compositions thereof.
Type: Grant
Filed: April 15, 2010
Issued: April 1, 2014
Assignee: The Regents of the University of California
Inventors: Roger Y. Tsien, Quyen T. Nguyen, Michael Whitney
Patent number: 8679742
Abstract: This invention provides tandem fluorescent protein construct including a donor fluorescent protein moiety, an acceptor fluorescent protein moiety and a linker moiety that couples the donor and acceptor moieties. The donor and acceptor moieties exhibit fluorescence resonance energy transfer which is eliminated upon cleavage. The constructs are useful in enzymatic assays.
Type: Grant
Filed: November 4, 2009
Issued: March 25, 2014
Assignees: The Regents of the University of California, Life Technologies Corporation
Inventors: Roger Y. Tsien, Roger Heim, Andrew Cubitt
Patent number: 8669074
Abstract: A chimeric phosphorylation indicator (CPI) as provided herein can contain a donor molecule, a phosphorylatable domain, a phosphoaminoacid binding domain (PAABD), and an acceptor molecule. Where the phosphorylatable domain is phosphorylatable by protein kinase C (PKC), the CPI is a c-kinase activity reporter (CKAR). Donor and acceptor molecules may be, independently, fluorescent proteins such as non-oligomerizing fluorescent proteins. A CPI can contain a phosphorylatable polypeptide and a fluorescent protein; the phosphorylatable polypeptide may be contained within the sequence of the fluorescent protein, or the fluorescent protein may be contained within the sequence of the phosphorylatable polypeptide. The spatiotemporal properties of the PKC signal pathway may be tested with CKAR, calcium-sensing fluorophores and FRET-based translocation assays. Polynucleotides encoding such CPIs, and kits containing the indicators and/or the polynucleotides, are provided.
Type: Grant
Filed: May 28, 2004
Issued: March 11, 2014
Assignee: The Regents of the University of California
Inventors: Jonathan D. Violin, Alexandra C. Newton, Roger Y. Tsien, Jin Zhang
Patent number: 8642561
Abstract: A generic structure for the peptides of the present invention includes A-X-B-C, where C is a cargo moiety, the B portion includes basic amino acids, X is a cleavable linker sequence, and the A portion includes acidic amino acids. The intact structure is not significantly taken up by cells; however, upon extracellular cleavage of X, the B-C portion is taken up, delivering the cargo to targeted cells. Cargo may be, for example, a contrast agent for diagnostic imaging, a chemotherapeutic drug, or a radiation-sensitizer for therapy. Cleavage of X allows separation of A from B, unmasking the normal ability of the basic amino acids in B to drag cargo C into cells near the cleavage event. X is cleaved extracellularly, preferably under physiological conditions. D-amino acids are preferred for the A and B portions, to minimize immunogenicity and nonspecific cleavage by background peptidases or proteases.
Type: Grant
Filed: December 7, 2011
Issued: February 4, 2014
Assignee: The Regents of the University of California
Inventors: Tao Jiang, Roger Y. Tsien
Application number: 20130330718
Abstract: The present invention provides miniSOG proteins, polynucleotides, and methods of use. When expressed in a bacterial or mammalian cell, miniSOG proteins spontaneously incorporate flavin mononucleotide and produce fluorescence and singlet oxygen upon excitation. Uses include optical and electron microscope imaging, in vivo imaging, detection and localization of protein-protein interactions, and photoablation.
Type: Application
Filed: December 7, 2011
Issued: December 12, 2013
Assignee: The Regents of the University of California
Inventors: Xiaokun Shu, Roger Y. Tsien
Application number: 20130078188
Abstract: The invention provides compositions useful as molecular probes. In particular, the invention provides activatable cell penetrating peptides comprising a fluorescence donor and a fluorescence acceptor. Exemplary fluorescence donors and fluorescence acceptors include compounds derived from cyanine. Also provided are ratiometric, multispectral, and excitation lifetime imaging methods for detecting the molecular probes provided herein.
Type: Application
Filed: August 3, 2012
Issued: March 28, 2013
Assignee: The Regents of the University of California
Inventors: Roger Y. Tsien, Tao Jiang, Elamprakash N. Savariar
Application number: 20130066402
Abstract: The invention provides engineered red-shifted channelrhodopsin variants. In some embodiments, the channelrhodopsin variants are characterized by improved membrane trafficking, expression, and/or unique spectral and kinetic properties.
Type: Application
Filed: August 17, 2012
Issued: March 14, 2013
Assignee: The Regents of the University of California
Inventors: John Yu-luen Lin, Roger Y. Tsien
Application number: 20130004960
Abstract: The present invention provides a method for reducing undesirable light emission from a sample using at least one photon producing agent and at least one photon reducing agent (e.g. dye-based photon reducing agents). The present invention further provides a method for reducing undesirable light emission from a sample (e.g., a biochemical or cellular sample) with at least one photon producing agent and at least one collisional quencher. The present invention also provides a method for reducing undesirable light emission from a sample (e.g., a biochemical or cellular sample) with at least one photon producing agent and at least one quencher, such as an electronic quencher. The present invention also provides a system and method of screening test chemicals in fluorescent assays using photon reducing agents. The present invention also provides compositions, pharmaceutical compositions, and kits for practicing these methods.
Type: Application
Filed: April 2, 2012
Issued: January 3, 2013
Assignee: Life Technologies Corporation
Inventors: Tom KNAPP, Gregor Zlokarnik, Paul Negulesou, Roger Y. Tsien, Timothy James Rink
Application number: 20120251445
Abstract: A generic structure for the peptides of the present invention includes A-X-B-C, where C is a cargo moiety, the B portion includes basic amino acids, X is a cleavable linker sequence, and the A portion includes acidic amino acids. The intact structure is not significantly taken up by cells; however, upon extracellular cleavage of X, the B-C portion is taken up, delivering the cargo to targeted cells. Cargo may be, for example, a contrast agent for diagnostic imaging, a chemotherapeutic drug, or a radiation-sensitizer for therapy. Cleavage of X allows separation of A from B, unmasking the normal ability of the basic amino acids in B to drag cargo C into cells near the cleavage event. X is cleaved extracellularly, preferably under physiological conditions. D-amino acids are preferred for the A and B portions, to minimize immunogenicity and nonspecific cleavage by background peptidases or proteases.
Type: Application
Filed: December 7, 2011
Issued: October 4, 2012
Assignee: The Regents of the University of California
Inventors: Tao Jiang, Roger Y. Tsien
Application number: 20120148499
Abstract: The present invention provides methods for guiding preservation of neurons or nerves during surgery by administering a fluorescently-labeled peptide or aptamer that specifically binds to the neurons or nerves. The invention further provides targeting molecules of fluorescently-labeled peptides or aptamers that specifically bind to neurons or nerves and for compositions thereof.
Type: Application
Filed: April 15, 2010
Issued: June 14, 2012
Assignee: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
Inventors: Roger Y. Tsien, Quyen T. Nguyen, Michael Whitney
Patent number: 8110554
Abstract: A generic structure for the peptides of the present invention includes A-X-B-C, where C is a cargo moiety, the B portion includes basic amino acids, X is a cleavable linker sequence, and the A portion includes acidic amino acids. The intact structure is not significantly taken up by cells; however, upon extracellular cleavage of X, the B-C portion is taken up, delivering the cargo to targeted cells. Cargo may be, for example, a contrast agent for diagnostic imaging, a chemotherapeutic drug, or a radiation-sensitizer for therapy. Cleavage of X allows separation of A from B, unmasking the normal ability of the basic amino acids in B to drag cargo C into cells near the cleavage event. X is cleaved extracellularly, preferably under physiological conditions. D-amino acids are preferred for the A and B portions, to minimize immunogenicity and nonspecific cleavage by background peptidases or proteases.
Type: Grant
Filed: October 2, 2008
Issued: February 7, 2012
Assignee: The Regents of the University of California
Inventors: Tao Jiang, Roger Y. Tsien
Application number: 20120014873
Abstract: A generic structure for the peptides of the present invention includes A-X-B-C, where C is a cargo moiety, the B portion includes basic amino acids, X is a cleavable linker sequence, and the A portion includes acidic amino acids. The intact structure is not significantly taken up by cells; however, upon extracellular cleavage of X, the B-C portion is taken up, delivering the cargo to targeted cells. Cargo may be, for example, a contrast agent for diagnostic imaging, a chemotherapeutic drug, or a radiation-sensitizer for therapy. X may be cleaved extracellularly or intracellularly. The molecules of the present invention may be linear, cyclic, branched, or have a mixed structure.
Type: Application
Filed: June 7, 2011
Issued: January 19, 2012
Assignee: The Regents of the University of California
Inventors: Tao Jiang, Emilia S. Olson, Michael Whitney, Roger Y. Tsien
Patent number: 8071789
Abstract: The present invention features biarsenical molecules. Target sequences that specifically react with the biarsenical molecules are also included. The present invention also features kits that include biarsenical molecules and target sequences. Tetraarsenical molecules are also featured in the invention.
Type: Grant
Filed: March 18, 2009
Issued: December 6, 2011
Assignee: The Regents of the University of California
Inventors: Roger Y. Tsien, B. Albert Griffin
Patent number: 8071761
Abstract: Substrates for ?-lactamase of the general formula I in which one of X and Y is a fluorescent donor moiety and the other is a quencher (which may or may not re-emit); R? is selected from the group consisting of H, lower (i.e., alkyl of 1 to about 5 carbon atoms) and (CH2)nOH, in which n is 0 or an integer from 1 to 5; R? is selected from the group consisting of H, physiologically acceptable metal and ammonium cations, —CHR2OCO(CH2)nCH3, —CHR2OCOC (CH3)3, acylthiomethyl, acyloxy-alpha-benzyl, delta-butyrolactonyl, methoxycarbonyloxymethyl, phenyl, methylsulphinylmethyl, beta-morpholinoethyl, dialkylaminoethyl, acyloxyalkyl, dialkylaminocarbonyloxymethyl and aliphatic, in which R2 is selected from the group consisting of H and lower alkyl; A is selected from the group consisting of S, O, SO, SO2 and CH2; and Z? and Z? are linkers for the fluorescent donor and quencher moieties.
Type: Grant
Filed: November 29, 2006
Issued: December 6, 2011
Assignee: The Regents of the University of California
Inventors: Roger Y. Tsien, Gregor Zlokarnik
Patent number: 7993879
Abstract: Fluorescent indicators including a binding protein moiety, a donor fluorescent protein moiety, and an acceptor fluorescent protein moiety are described. The binding protein moiety has an analyte-binding region which binds an analyte and causes the indicator to change conformation upon exposure to the analyte. The donor moiety and the acceptor moiety change position relative to each other when the analyte binds to the analyte-binding region. The donor moiety and the acceptor moiety exhibit fluorescence resonance energy transfer when the donor moiety is excited and the distance between the donor moiety and the acceptor moiety is small. The indicators can be used to measure analyte concentrations in samples, such as calcium ion concentrations in cells.
Type: Grant
Filed: January 17, 2006
Issued: August 9, 2011
Assignee: The Regents of the University of California
Inventors: Roger Y. Tsien, Atsushi Miyawaki
Application number: 20110172139
Abstract: A generic structure for the peptides of the present invention includes A-X-B-C, where C is a cargo moiety, the B portion includes basic amino acids, X is a cleavable linker sequence, and the A portion includes acidic amino acids. The intact structure is not significantly taken up by cells; however, upon extracellular cleavage of X, the B-C portion is taken up, delivering the cargo to targeted cells. Cargo may be, for example, a contrast agent for diagnostic imaging, a chemotherapeutic drug, or a radiation-sensitizer for therapy. Cleavage of X allows separation of A from B, unmasking the normal ability of the basic amino acids in B to drag cargo C into cells near the cleavage event. X is cleaved extracellularly, preferably under physiological conditions. D-amino acids are preferred for the A and B portions, to minimize immunogenicity and nonspecific cleavage by background peptidases or proteases.
Type: Application
Filed: October 2, 2008
Issued: July 14, 2011
Assignee: The Regents of the University of California
Inventors: Tao Jiang, Roger Y. Tsien
Application number: 20110076711
Abstract: The present invention provides a method for reducing undesirable light emission from a sample using at least one photon producing agent and at least one photon reducing agent (e.g. dye-based photon reducing agents). The present invention further provides a method for reducing undesirable light emission from a sample (e.g., a biochemical or cellular sample) with at least one photon producing agent and at least one collisional quencher. The present invention also provides a method for reducing undesirable light emission from a sample (e.g., a biochemical or cellular sample) with at least one photon producing agent and at least one quencher, such as an electronic quencher. The present invention also provides a system and method of screening test chemicals in fluorescent assays using photon reducing agents. The present invention also provides compositions, pharmaceutical compositions, and kits for practicing these methods.
Type: Application
Filed: August 23, 2010
Issued: March 31, 2011
Assignee: LIFE TECHNOLOGIES CORPORATION
Inventors: Tom KNAPP, Gregor Zlokarnik, Paul Negulescu, Roger Y. Tsien, Timothy James Rink
Patent number: 7906636
Abstract: The present invention relates generally to fluorescent proteins and fluorescent protein variants, and more specifically to monomeric and dimeric forms of Anthozoan fluorescent proteins. In one aspect, the present invention provides variants of fluorescent proteins, where the variants have a reduced propensity to tetramerize, and form dimeric or monomeric structures. In a further aspect, the present invention provides variants of fluorescent proteins, the variants being characterized by more efficient maturation than corresponding fluorescent proteins from which they are derived. The invention also relates to methods of making and using such fluorescent proteins and fluorescent protein variants, including fluorescent protein monomers and dimers.
Type: Grant
Filed: November 13, 2009
Issued: March 15, 2011
Assignee: The Regents of the University of California
Inventors: Roger Y. Tsien, Robert E. Campbell, Nathan C. Shaner
Patent number: 7854898
Abstract: The present invention relates to multi-well platforms, lids, caddies and any combination thereof. The multi-well platforms comprise a plurality of wells that can be of any shape and can be arranged in any ornamental pattern. The lid comprises an area corresponding to the well field. The caddy has a footprint approximately that of a standard 96-well microtiter plate. When the multi-well platform is engaged with the caddy, the wells of the well-field of the multi-well platform are preferably not obscured by the caddy when viewed from the bottom of the combination.
Type: Grant
Filed: November 14, 2008
Issued: December 21, 2010
Assignee: Nexus Biosystems, Inc.
Inventors: Andrew A. Pham, Peter J. Coassin, Alec Tate Harootunian, Peter N. Pham, Harry Stylli, Roger Y. Tsien