WO2012061684A1 - Upconversion of light for use in optogenetic methods - Google Patents

Upconversion of light for use in optogenetic methods Download PDF

Info

Publication number
WO2012061684A1
WO2012061684A1 PCT/US2011/059287 US2011059287W WO2012061684A1 WO 2012061684 A1 WO2012061684 A1 WO 2012061684A1 US 2011059287 W US2011059287 W US 2011059287W WO 2012061684 A1 WO2012061684 A1 WO 2012061684A1
Authority
WO
WIPO (PCT)
Prior art keywords
light
nanoparticles
responsive
opsin
spectrum
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2011/059287
Other languages
English (en)
French (fr)
Inventor
Polina Anikeeva
Karl Deisseroth
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Leland Stanford Junior University
Original Assignee
Leland Stanford Junior University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to CA2817175A priority Critical patent/CA2817175C/en
Priority to JP2013537855A priority patent/JP6145043B2/ja
Priority to CN201180060040.XA priority patent/CN103313752B/zh
Priority to EP11838859.4A priority patent/EP2635341B1/en
Priority to AU2011323231A priority patent/AU2011323231B2/en
Priority to US13/882,703 priority patent/US9522288B2/en
Application filed by Leland Stanford Junior University filed Critical Leland Stanford Junior University
Priority to ES11838859.4T priority patent/ES2690172T3/es
Publication of WO2012061684A1 publication Critical patent/WO2012061684A1/en
Anticipated expiration legal-status Critical
Priority to AU2016202003A priority patent/AU2016202003B2/en
Priority to US15/214,403 priority patent/US10252076B2/en
Priority to US16/267,144 priority patent/US20190217118A1/en
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N5/0613—Apparatus adapted for a specific treatment
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61D—VETERINARY INSTRUMENTS, IMPLEMENTS, TOOLS, OR METHODS
    • A61D7/00—Devices or methods for introducing solid, liquid, or gaseous remedies or other materials into or onto the bodies of animals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/177—Receptors; Cell surface antigens; Cell surface determinants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A61K41/0038—Radiosensitizing, i.e. administration of pharmaceutical agents that enhance the effect of radiotherapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
    • A61K41/008—Two-Photon or Multi-Photon PDT, e.g. with upconverting dyes or photosensitisers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A61K48/0083—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the administration regime
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1611—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N5/0613—Apparatus adapted for a specific treatment
    • A61N5/062—Photodynamic therapy, i.e. excitation of an agent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N5/0613—Apparatus adapted for a specific treatment
    • A61N5/0622—Optical stimulation for exciting neural tissue
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N2005/0658—Radiation therapy using light characterised by the wavelength of light used
    • A61N2005/0659—Radiation therapy using light characterised by the wavelength of light used infrared
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N2005/0658—Radiation therapy using light characterised by the wavelength of light used
    • A61N2005/0662—Visible light
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N2005/0658—Radiation therapy using light characterised by the wavelength of light used
    • A61N2005/0662—Visible light
    • A61N2005/0663—Coloured light
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
    • C12N2750/00011—Details
    • C12N2750/14011—Parvoviridae
    • C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
    • C12N2750/14141—Use of virus, viral particle or viral elements as a vector
    • C12N2750/14143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector

Definitions

  • FIG. 3 depicts a system that uses multiple light sources, consistent with an embodiment of the present disclosure.
  • biocompatible material is transparent, so that visible light produced by the upconversion of IR or NIR electromagnetic radiation by the lanthanide-doped nanoparticles can reach the light-responsive opsin proteins expressed on the surface of the neural cell of interest.
  • the biocompatible materials used to embed or trap the lanthanide-doped nanoparticles can include, but are not limited to, Ioplex materials and other hydrogels such as those based on 2-hydroxyethyl methacrylate or acrylamide, and poly ether polyurethane ureas (PEUU) including Biomer (Ethicon Corp.), Avcothane (Avco-Everrett Laboratories), polyethylene, polypropylene, polytetrafluoroethylene (Gore-TexTM), poly(vinylchloride),
  • Light-responsive opsins that may be used in the present invention include opsins that induce hyperpolarization in neurons by light and opsins that induce depolarization in neurons by light. Examples of opsins are shown in Tables 1 and 2 below. Table 1 shows identified opsins for inhibition of cellular activity across the visible spectrum:
  • Table 2 shows identified opsins for excitation and modulation across the visible spectrum:
  • a light-responsive opsin (such as NpHR, BR, AR, GtR3, Mac, ChR2, VChRl, DChR, and ChETA) includes naturally occuixing protein and functional variants, fragments, fusion proteins comprising the fragments, or the full length protein.
  • the signal peptide may be deleted.
  • a variant may have an amino acid sequence at least about any of 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the naturally occurring protein sequence.
  • a functional variant may have the same or similar hyperpolarization function or depolarization function as the naturally occurring protein.
  • the present disclosure provides for the modification of light-responsive opsin proteins expressed in a cell by the addition of one or more amino acid sequence motifs which enhance transport to the plasma membranes of mammalian cells.
  • Light-responsive opsin proteins having components derived from evolutionarily simpler organisms may not be expressed or tolerated by mammalian cells or may exhibit impaired subcellular localization when expressed at high levels in mammalian cells. Consequently, in some embodiments, the light- responsive opsin proteins expressed in a cell can be fused to one or more amino acid sequence motifs selected from the group consisting of a signal peptide, an endoplasmic reticulum (ER) export signal, a membrane trafficking signal, and/or an N- terminal golgi export signal.
  • ER endoplasmic reticulum
  • the one or more amino acid sequence motifs which enhance light- responsive opsin protein transport to the plasma membranes of mammalian cells can be fused to the N-terminus, the C-terminus, or to both the N- and C-terminal ends of the light- responsive opsin protein.
  • the light- responsive opsin protein and the one or more amino acid sequence motifs may be separated by a linker.
  • the light- responsive opsin protein can be modified by the addition of a trafficking signal (ts) which enhances transport of the protein to the cell plasma membrane.
  • the trafficking signal can be derived from the amino acid sequence of the human inward rectifier potassium channel Kir2.1.
  • the trafficking signal can comprise the amino acid sequence KSRITSEGEYIPLDQIDrNV.
  • the signal peptide sequence in the protein can be deleted or substituted with a signal peptide sequence from a different protein.
  • Light-responsive chloride pumps
  • the light-responsive opsin proteins described herein are light- responsive chloride pumps.
  • one or more members of the Halorhodopsin family of light-responsive chloride pumps are expressed on the plasma membranes of neurons of the central and peripheral nervous systems.
  • said one or more light-responsive chloride pump proteins expressed on the plasma membranes of nerve cells of the central or peripheral nervous systems can be derived from Natronomonas pharaonis.
  • the light- responsive chloride pump proteins can be responsive to amber light as well as red light and can mediate a hyperpolarizing current in the intemeuron when the light-responsive chloride pump proteins are illuminated with amber or red light.
  • the wavelength of light which can activate the light-responsive chloride pumps can be between about 580 and about 630 nm. In some embodiments, the light can be at a wavelength of about 590 nm or the light can have a wavelength greater than about 630 nm ⁇ e.g. less than about 740 nm).
  • the light has a wavelength of around 630 nm.
  • the light-responsive chloride pump protein can hyperpolarize a neural membrane for at least about 90 minutes when exposed to a continuous pulse of light.
  • the light-responsive chloride pump protein can comprise an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence shown in SEQ ID NO: 1.
  • the light-responsive chloride pump protein can comprise substitutions, deletions, and/or insertions introduced into a native amino acid sequence to increase or decrease sensitivity to light, increase or decrease sensitivity to particular wavelengths of light, and/or increase or decrease the ability of the light-responsive protein to regulate the polarization state of the plasma membrane of the cell.
  • the light-responsive chloride pump protein contains one or more conservative amino acid substitutions.
  • the light-responsive protein contains one or more non-conservative amino acid substitutions.
  • the light- responsive protein comprising substitutions, deletions, and/or insertions introduced into the native amino acid sequence suitably retains the ability to hyperpolarize the plasma membrane of a neuronal cell in response to light.
  • the light-responsive chloride pump protein can comprise a core amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence shown in SEQ ID NO: 1 and an endoplasmic reticulum (ER) export signal.
  • This ER export signal can be fused to the C- terminus of the core amino acid sequence or can be fused to the N-terminus of the core amino acid sequence.
  • the ER export signal is linked to the core amino acid sequence by a linker.
  • the linker can comprise any of about 5, 10, 20, 30, 40, 50, 75, 100, 125, 150, 175, 200, 225, 250, 275, 300, 400, or 500 amino acids in length.
  • the linker may further comprise a fluorescent protein, for example, but not limited to, a yellow fluorescent protein, a red fluorescent protein, a green fluorescent protein, or a cyan fluorescent protein.
  • the ER export signal can comprise the amino acid sequence FXYENE, where X can be any amino acid.
  • the ER export signal can comprise the amino acid sequence VXXSL, where X can be any amino acid.
  • the ER export signal can comprise the amino acid sequence FCYENEV.
  • the light-responsive chloride pump proteins provided herein can comprise a light-responsive protein expressed on the cell membrane, wherein the protein comprises a core amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence shown in SEQ ID NO: 1 and a trafficking signal (e.g., which can enhance transport of the light-responsive chloride pump protein to the plasma membrane).
  • the trafficking signal may be fused to the C-terminus of the core amino acid sequence or may be fused to the N-terminus of the core amino acid sequence.
  • the amino acid sequence at least 95% identical to the sequence shown in SEQ ID NO: 1 is linked to the ER export signal through a linker.
  • the ER export signal comprises the amino acid sequence FXYENE, where X can be any amino acid.
  • the ER export signal comprises the amino acid sequence VXXSL, where X can be any amino acid.
  • the ER export signal comprises the amino acid sequence FCYENEV.
  • the NpHR opsin protein comprises an amino acid sequence at least 95% identical to the sequence shown in SEQ ID NO:l, an ER export signal, and a membrane trafficking signal.
  • the NpHR opsin protein comprises, from the N-terminus to the C-terminus, the amino acid sequence at least 95% identical to the sequence shown in SEQ ID NO: 1, the ER export signal, and the membrane trafficking signal.
  • the NpHR opsin protein comprises, from the N-terminus to the C-terminus, the amino acid sequence at least 95% identical to the sequence shown in SEQ ID NO:l, the membrane trafficking signal, and the ER export signal.
  • the membrane trafficking signal is derived from the amino acid sequence of the human inward rectifier potassium channel Kir2.1.
  • the membrane trafficking signal comprises the amino acid sequence K S R I T S E G E Y I P L D Q I D I N V.
  • the membrane frafficking signal is linked to the amino acid sequence at least 95% identical to the sequence shown in SEQ ID NO: 1 by a linker.
  • the membrane trafficking signal is linked to the ER export signal through a linker.
  • the linker may comprise any of 5, 10, 20, 30, 40, 50, 75, 100, 125, 150, 175, 200, 225, 250, 275, 300, 400, or 500 amino acids in length.
  • the linker may further comprise a fluorescent protein, for example, but not limited to, a yellow fluorescent protein, a red fluorescent protein, a green fluorescent protein, or a cyan fluorescent protein.
  • the light-responsive opsin protein further comprises an N-terminal signal peptide.
  • the light-responsive opsin protein comprises the amino acid sequence of SEQ ID NO:2.
  • the light-responsive opsin protein comprises the amino acid sequence of SEQ ID NO:3.
  • the light-responsive proton pump protein can be responsive to blue light and can be derived from Guillardia theta, wherein the proton pump protein can be capable of mediating a hyperpolarizing current in the cell when the cell is illuminated with blue light.
  • the light can have a wavelength between about 450 and about 495 nm or can have a wavelength of about 490 nm.
  • the light- responsive proton pump protein can comprise an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence shown in SEQ ID NO:4.
  • the light-responsive proton pump protein can additionally comprise substitutions, deletions, and/or insertions introduced into a native amino acid sequence to increase or decrease sensitivity to light, increase or decrease sensitivity to particular wavelengths of light, and/or increase or decrease the ability of the light- responsive proton pump protein to regulate the polarization state of the plasma membrane of the cell. Additionally, the light-responsive proton pump protein can contain one or more conservative amino acid substitutions and/or one or more non-conservative amino acid substitutions.
  • the light-responsive proton pump protein comprising substitutions, deletions, and/or insertions introduced into the native amino acid sequence suitably retains the ability to hyperpolarize the plasma membrane of a neuronal cell in response to light.
  • the light-responsive proton pump protein can comprise a core amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence shown in SEQ ID NO:
  • the light-responsive proton pump protein comprises an N-terminal signal peptide and a C-terminal ER export signal. In some embodiments, the light- responsive proton pump protein comprises an N-terminal signal peptide and a C-terminal trafficking signal. In some embodiments, the light-responsive proton pump protein comprises an N-terminal signal peptide, a C-terminal ER Export signal, and a C-terminal trafficking signal.
  • the light-responsive proton pump protein comprises a C-terminal ER Export signal and a C-terminal trafficking signal.
  • the C-terminal ER Export signal and the C-terminal trafficking signal are linked by a linker.
  • the linker can comprise any of about 5, 10, 20, 30, 40, 50, 75, 100, 125, 150, 175, 200, 225, 250, 275, 300, 400, or 500 amino acids in length.
  • the linker may further comprise a fluorescent protein, for example, but not limited to, a yellow fluorescent protein, a red fluorescent protein, a green fluorescent protein, or a cyan fluorescent protein.
  • the ER Export signal is more C-terminally located than the trafficking signal.
  • the trafficking signal is more C-terminally located than the ER Export signal.
  • isolated polynucleotides encoding any of the light- responsive proton pump proteins described herein, such as a light-responsive proton pump protein comprising a core amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence shown in SEQ ID NO:4.
  • expression vectors such as a viral vector described herein
  • a polynucleotide encoding the proteins described herein, such as a light- responsive proton pump protein comprising a core amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence shown in SEQ ID NO:4.
  • the polynucleotides may be used for expression of the light- responsive proton pumps in neural cells of the central or peripheral nervous systems.
  • the light-activated cation channel protein can be derived from Chlamydomonas reinhardtii, wherein the cation channel protein can be capable of mediating a depolarizing current in the cell when the cell is illuminated with light.
  • the light-activated cation channel protein can comprise an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence shown in SEQ ID NO:5.
  • the light used to activate the light- activated cation channel protein derived from Chlamydomonas reinhardtii can have a wavelength between about 460 and about 495 nm or can have a wavelength of about 480 nm. Additionally, the light can have an intensity of at least about 100 Hz. In some embodiments, activation of the light-activated cation channel derived from Chlamydomonas reinhardtii, wherein the cation channel protein can be capable of mediating a depolarizing
  • Chlamydomonas reinhardtii with light having an intensity of 100 Hz can cause depolarization-induced synaptic depletion of the neurons expressing the light-activated cation channel.
  • the light-activated cation channel protein can additionally comprise substitutions, deletions, and/or insertions introduced into a native amino acid sequence to increase or decrease sensitivity to light, increase or decrease sensitivity to particular wavelengths of light, and/or increase or decrease the ability of the light-activated cation channel protein to regulate the polarization state of the plasma membrane of the cell.
  • the light-activated cation channel protein can contain one or more conservative amino acid substitutions and/or one or more non-conservative amino acid substitutions.
  • the light-activated proton pump protein comprising substitutions, deletions, and/or insertions introduced into the native amino acid sequence suitably retains the ability to depolarize the plasma membrane of a neuronal cell in response to light.
  • the light-activated cation channel protein can be a step function opsin (SFO) protein or a stabilized step function opsin (SSFO) protein that can have specific amino acid substitutions at key positions throughout the retinal binding pocket of the protein.
  • the SFO protein can have a mutation at amino acid residue C128 of SEQ ID NO:5.
  • the SFO protein has a C128A mutation in SEQ ID NO:5.
  • the SFO protein has a C128S mutation in SEQ ID NO:5.
  • the SFO protein has a C128T mutation in SEQ ID NO:5.
  • the SFO protein can comprise an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence shown in SEQ ID NO:6.
  • the SSFO protein can have a mutation at amino acid residue D 156 of SEQ ID NO:5. In other embodiments, the SSFO protein can have a mutation at both amino acid residues C128 and D156 of SEQ ID NO:5. In one embodiment, the SSFO protein has an C128S and a D156A mutation in SEQ ID NO:5. In another embodiment, the SSFO protein can comprise an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence shown in SEQ ID NO:7.
  • the SFO or SSFO proteins provided herein can be capable of mediating a depolarizing current in the cell when the cell is illuminated with blue light.
  • the light can have a wavelength of about 445 nm.
  • the light can have an intensity of about 100 FIz.
  • activation of the SFO or SSFO protein with light having an intensity of 100 FIz can cause depolarization-induced synaptic depletion of the neurons expressing the SFO or SSFO protein.
  • each of the disclosed step function opsin and stabilized step function opsin proteins can have specific properties and characteristics for use in depolarizing the membrane of a neuronal cell in response to light.
  • the light-activated cation channel protein can be a CI VI chimeric protein derived from the VChRl protein of Volvox carteri and the ChRl protein from Chlamydomonas reinhardti, wherein the protein comprises the amino acid sequence of VChRl having at least the first and second transmembrane helices replaced by the first and second transmembrane helices of ChRl; is responsive to light; and is capable of mediating a depolarizing current in the cell when the cell is illuminated with light.
  • the CI VI protein can further comprise a replacement within the intracellular loop domain located between the second and third transmembrane helices of the chimeric light responsive protein, wherein at least a portion of the intracellular loop domain is replaced by the corresponding portion from ChRl.
  • the portion of the intracellular loop domain of the CI VI chimeric protein can be replaced with the corresponding portion from ChRl extending to amino acid residue A 145 of the ChRl .
  • the CI VI chimeric protein can further comprise a replacement within the third transmembrane helix of the chimeric light responsive protein, wherein at least a portion of the third transmembrane helix is replaced by the corresponding sequence of ChRl .
  • the portion of the intracellular loop domain of the C1V1 chimeric protein can be replaced with the corresponding portion from ChRl extending to amino acid residue Wl 63 of the ChRl .
  • the C 1 VI chimeric protein can comprise an amino acid sequence at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence shown in SEQ ID NO:8.
  • the CI VI protein can mediate a depolarizing current in the cell when the cell is illuminated with green light.
  • the light can have a wavelength of between about 540 nm to about 560 nm. In some embodiments, the light can have a wavelength of about 542 nm.
  • the CI VI chimeric protein is not capable of mediating a depolarizing current in the cell when the cell is illuminated with violet light. In some embodiments, the chimeric protein is not capable of mediating a depolarizing current in the cell when the cell is illuminated with light having a wavelength of about 405 nm. Additionally, the light can have an intensity of about 100 Hz.
  • activation of the CI VI chimeric protein with light having an intensity of 100 Hz can cause depolarization-induced synaptic depletion of the neurons expressing the CI VI chimeric protein.
  • the disclosed CI VI chimeric protein can have specific properties and characteristics for use in depolarizing the membrane of a neuronal cell in response to light.
  • the invention can include polypeptides comprising substituted or mutated amino acid sequences, wherein the mutant polypeptide retains the characteristic light-responsive nature of the precursor CI VI chimeric polypeptide but may also possess altered properties in some specific aspects.
  • the mutant light-activated C1V1 chimeric proteins described herein can exhibit an increased level of expression both within an animal cell or on the animal cell plasma membrane; an altered responsiveness when exposed to different wavelengths of light, particularly red light; and/or a combination of traits whereby the chimeric CI VI polypeptide possess the properties of low
  • the CI VI -El 62 mutant chimeric protein is capable of mediating a depolarizing current in the cell when the cell is illuminated with light.
  • the C 1 V 1 -E 122/E 162 mutant chimeric protein is capable of mediating a depolarizing current in the cell when the cell is illuminated with light.
  • the light can be green light.
  • the light can have a wavelength of between about 540 nm to about 560 nm.
  • the light can have a wavelength of about 546 nm.
  • the C1V1-E122/E162 mutant chimeric protein does not mediate a depolarizing current in the cell when the cell is illuminated with violet light.
  • the chimeric protein does not mediate a depolarizing current in the cell when the cell is illuminated with light having a
  • the vector is a recombinant AAV vector.
  • AAV vectors are DNA viruses of relatively small size that can integrate, in a stable and site-specific manner, into the genome of the cells that they infect. They are able to infect a wide spectrum of cells without inducing any effects on cellular growth, morphology or differentiation, and they do not appear to be involved in human pathologies.
  • the AAV genome has been cloned, sequenced and characterized. It encompasses approximately 4700 bases and contains an inverted terminal repeat (TTR) region of approximately 145 bases at each end, which serves as an origin of replication for the virus.
  • TTR inverted terminal repeat
  • Other methods to deliver the light-responsive opsin proteins to the nerves of interest can also be used, such as, but not limited to, transfection with ionic lipids or polymers, electroporation, optical transfection, impalefection, or via gene gun.
  • the operational frequency of the radio wave can be between about 1 and 20 MHz, inclusive, including any values in between these numbers (for example, about 1 MHz, about 2 MHz, about 3 MHz, about 4 MHz, about 5 MHz, about 6 MHz, about 7 MHz, about 8 MHz, about 9 MHz, about 10 MHz, about 11 MHz, about 12 MHz, about 13 MHz, about 14 MHz, about 15 MHz, about 16 MHz, about 17 MHz, about 18 MHz, about 19 MHz, or about 20 MHz).
  • the intensity of the IR or NIR electromagnetic radiation reaching the neural cells (such as neural cells expressing one or more light-responsive opsin proteins) produced by the IR or NIR electromagnetic radiation source has an intensity of any of about 0.05 mW/mm 2 , 0.1 mW/mm 2 , 0.2 mW/mm 2 , 0.3 mW/mm 2 , 0.4 mW/mm 2 , 0.5 mW/mm 2 , about 0.6 mW/mm 2 , about 0.7 mW/mrn 2 , about 0.8 mW/mm 2 , about 0.9 mW/mm 2 , about 1.0 mW/mm 2 , about 1.1 mW/mm 2 , about 1.2 mW/mm 2 , about 1.3 mW/mm 2 , about 1.4 mW/mm 2 , about 1.5 mW/mm 2 , about 1.6 mW/mrn 2 , about 1.7 mW/mm 2 , about 1.8 m
  • electromagnetic radiation produced has a wavelength between 700 nm and 1000 nm.
  • the IR or NIR electromagnetic radiation source is held against the skin in a bracelet or cuff configuration.
  • IR or NIR electromagnetic radiation sources particularly those small enough to be implanted under the skin, can be found in U.S. Patent Application Publication Nos.: 2009/0143842, 2011/0152969, 2011/0144749, and 2011/0054305, the disclosures of each of which are incorporated by reference herein in their entireties.
  • the lanthanide-doped nanoparticles disclosed herein can be exposed to higher wavelength light in the visible spectrum (such as red light) to upconvert the higher wavelength visible light into lower wavelength visible light (such as blue or green light).
  • red light a visible light
  • visible light typically does so in higher wavelengths which correspond to red light (for example, between about 620 nm to 740 nm).
  • the lanthanide-doped nanoparticles disclosed herein can additionally be used in combination with optical sources of visible light to upshift wavelengths corresponding to red light into wavelengths corresponding to green or blue light (for example, between about 440 nm and 570 nm).
  • optical sources of visible light for example, between about 440 nm and 570 nm.
  • Examples of light stimulation devices, including light sources, can be found in International Patent Application Nos.: PCT/US08/50628 and
  • IR infrared
  • NIR near infrared
  • Also provided herein is a method to depolarize the plasma membrane of a neural cell in an individual comprising administering a polynucleotide encoding a light-responsive opsin to a neural cell in the brain of an individual, wherein the light-responsive protein is expressed on the plasma membrane of the neural cell and the opsin is capable of inducing membrane depolarization of the neural cell when illuminated with light administering a plurality of lanthanide-doped nanoparticles in proximity to the neural cell; and exposing the plurality of nanoparticles to electromagnetic radiation in the infrared (IR) or near (IR) spectrum, wherein the electromagnetic radiation in the IR or near IR spectrum is upconverted into light in the visible spectrum and the activation of the opsin by the light in the visible spectrum induces the depolarization of the plasma membrane.
  • IR infrared
  • IR infrared
  • IR infrared
  • the nanoparticles comprise
  • NaYF4 Yb/X/Gd, wherein X is Er, Tm, or Er/Tm.
  • the electromagnetic radiation in the IR or near IR spectrum can be upconverted into light having a wavelength of about 450 nm to about 550 nm.
  • the light can have wavelengths corresponding to red, yellow, amber, orange, green, or blue light.
  • the individual is a human or a non-human animal.
  • the neural cell is in the peripheral nervous system. In another embodiment, the neural cell is in the central nervous system.
  • IR infrared
  • NIR near infrared
  • Also provided herein is a method to hyperpolarize the plasma membrane of a neural cell in an individual comprising admimstering a polynucleotide encoding a light-responsive opsin to a neural cell in the brain of an individual, wherein the light-responsive protein is expressed on the plasma membrane of the neural cell and the opsin is capable of inducing membrane depolarization of the neural cell when illuminated with light administering a plurality of lanthanide-doped nanoparticles in proximity to the neural cell; and exposing the plurality of nanoparticles to electromagnetic radiation in the infrared (JR) or near (IR) spectrum, wherein the electromagnetic radiation in the IR or near IR spectrum is upconverted into light in the visible spectrum and the activation of the opsin by the light in the visible spectrum induces the hyperpolarization of the plasma membrane.
  • JR infrared
  • IR near
  • kits comprising polynucleotides encoding a light- responsive opsin protein (such as any of the light-responsive opsin proteins described herein) and lanthanide-doped nanoparticles for use in any of the methods disclosed herein to alter the membrane polarization state of one or more neurons of the central and/or peripheral nervous system.
  • the kits further comprise an infrared or near infrared electromagnetic radiation source.
  • the kits further comprise instructions for using the polynucleotides and lanthanide-doped nanoparticles described herein.
  • the lanthanide-doped nanoparticles described herein are embedded and/or trapped in a biocompatible material (such as any of the biocompatible materials described above).
  • minimally invasive delivery of light for example as can be useful for manipulation of neural circuits with optogenetics, using near infrared up-conversion nanocrystals.
  • This is used to avoid the implantation of light sources within living tissues, including, for example, a subject's brain.
  • Mammalian tissue has a transparency window in near infrared part of the spectrum (700- lOOOnm). Accordingly, aspects of the present disclosure relate to the use of nanoparticles for the purpose of using (near) infrared light to deliver energy into the depth of a brain by converting the infrared light into visible wavelengths at a site of interest.
  • delivering visible wavelengths at a site of interest within the brain is achieved through a process of optical upconversion in Lanthanide-doped
  • a single step surgery is performed to modify a target cell population and provide nanoparticles to convert near infrared light to visible light that stimulates the modified target cell population.
  • the surgeon injects both an adeno-associated virus carrying an opsin gene and a nanoparticle solution to a site of interest.
  • the battery has characteristics similar to those of a pacemaker battery.
  • a microcontroller can be used to control the battery to deliver energy to the LED at specified intervals, resulting in LED light pulses at specified intervals.
  • Optogenetics applied in vivo, relies on light delivery to specific neuron populations that can be located deep within the brain. Mammalian tissue is highly absorptive and scatters light in the visible spectrum. However, near infrared light is able to penetrate to deep levels of the brain without excessive absorption or scattering.
  • the system shown in FIG. 1 allows for delivery of light to a target cell deep within a patient's brain tissue.
  • the light responsive molecule can be specifically targeted to a neural cell type of interest.
  • the nanocrystals 112 are anchored to the neural cell with antibodies chosen based on the type of neural cell 114 being targeted.
  • Target neurons 214 express an opsin gene, allowing the neurons to be activated or inhibited, depending on which opsin, and what wavelength of light is absorbed by the neurons 214.
  • the target neurons 214 can be interspersed between other neurons 216.
  • target neurons 214 are coated with upconverting nanoparticles 210 that are anchored to the neural membrane via antibodies.
  • the nanoparticles 210 absorb IR photons and emit visible photons that are then absorbed by opsins triggering neural activation.
  • the antibodies used to anchor the nanoparticles 210 to the target neuron membranes are modified to attach to a specific membrane type. As shown in inset 202, the nanoparticles 210 are closely linked to the target neurons so that visible light photons emitted by the nanoparticles 210 are absorbed by the target neurons 214.
  • Nanoparticles located at the intersection 314 of the light from the different light sources 302-306 receive increased intensity of optical stimulus relative to other locations, including those locations within the path of light from a single light source.
  • the light intensity of each of the light sources can be set below a threshold level.
  • the threshold level can be set according to an amount of light necessary to cause the desired effect (e.g., excitation or inhibition) on the target cells.
  • the threshold level can be set to avoid adverse effects on non-targeted tissue (e.g., heating).
  • Various embodiments of the present disclosure are directed toward the use of nanocrystals that emit light at different wavelengths. This can be particularly useful when using multiple opsins having different light-absorption spectrums.
  • the nanocrystals can be targeted toward different opsins and/or placed in the corresponding locations.
  • Example 1 Use of lanthanide-doped nanoparticles in the use of optogenetics to hyperpolarize the cholinergic interneurons of the nucleus accumbens

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Biomedical Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biophysics (AREA)
  • Pathology (AREA)
  • Radiology & Medical Imaging (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Nanotechnology (AREA)
  • Zoology (AREA)
  • Biotechnology (AREA)
  • Molecular Biology (AREA)
  • General Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Wood Science & Technology (AREA)
  • Immunology (AREA)
  • Neurosurgery (AREA)
  • Medical Informatics (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Biochemistry (AREA)
  • Organic Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Cell Biology (AREA)
  • Virology (AREA)
  • Microbiology (AREA)
  • Dermatology (AREA)
  • Inorganic Chemistry (AREA)
  • Radiation-Therapy Devices (AREA)
  • Peptides Or Proteins (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
PCT/US2011/059287 2010-11-05 2011-11-04 Upconversion of light for use in optogenetic methods Ceased WO2012061684A1 (en)

Priority Applications (10)

Application Number Priority Date Filing Date Title
ES11838859.4T ES2690172T3 (es) 2010-11-05 2011-11-04 Conversión ascendente de la luz para su uso en métodos optogenéticos
JP2013537855A JP6145043B2 (ja) 2010-11-05 2011-11-04 光遺伝的方法で使用するための光の上方変換
CN201180060040.XA CN103313752B (zh) 2010-11-05 2011-11-04 用于光遗传学方法的光的上转换
EP11838859.4A EP2635341B1 (en) 2010-11-05 2011-11-04 Upconversion of light for use in optogenetic methods
AU2011323231A AU2011323231B2 (en) 2010-11-05 2011-11-04 Upconversion of light for use in optogenetic methods
CA2817175A CA2817175C (en) 2010-11-05 2011-11-04 Upconversion of light using lanthanide-doped nanoparticles for use in optogenetic methods
US13/882,703 US9522288B2 (en) 2010-11-05 2011-11-04 Upconversion of light for use in optogenetic methods
AU2016202003A AU2016202003B2 (en) 2010-11-05 2016-03-31 Upconversion of light for use in optogenetic methods
US15/214,403 US10252076B2 (en) 2010-11-05 2016-07-19 Upconversion of light for use in optogenetic methods
US16/267,144 US20190217118A1 (en) 2010-11-05 2019-02-04 Upconversion of light for use in optogenetic methods

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US41072910P 2010-11-05 2010-11-05
US61/410,729 2010-11-05

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US13/882,703 A-371-Of-International US9522288B2 (en) 2010-11-05 2011-11-04 Upconversion of light for use in optogenetic methods
US15/214,403 Continuation US10252076B2 (en) 2010-11-05 2016-07-19 Upconversion of light for use in optogenetic methods

Publications (1)

Publication Number Publication Date
WO2012061684A1 true WO2012061684A1 (en) 2012-05-10

Family

ID=46024837

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2011/059287 Ceased WO2012061684A1 (en) 2010-11-05 2011-11-04 Upconversion of light for use in optogenetic methods

Country Status (8)

Country Link
US (3) US9522288B2 (cg-RX-API-DMAC7.html)
EP (1) EP2635341B1 (cg-RX-API-DMAC7.html)
JP (2) JP6145043B2 (cg-RX-API-DMAC7.html)
CN (3) CN103313752B (cg-RX-API-DMAC7.html)
AU (2) AU2011323231B2 (cg-RX-API-DMAC7.html)
CA (1) CA2817175C (cg-RX-API-DMAC7.html)
ES (1) ES2690172T3 (cg-RX-API-DMAC7.html)
WO (1) WO2012061684A1 (cg-RX-API-DMAC7.html)

Cited By (35)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2547762A4 (en) * 2010-03-17 2013-09-04 Univ Leland Stanford Junior LIGHT-SENSITIVE ION-TURNING MOLECULES
US8603790B2 (en) 2008-04-23 2013-12-10 The Board Of Trustees Of The Leland Stanford Junior University Systems, methods and compositions for optical stimulation of target cells
EP2635108A4 (en) * 2010-11-05 2014-02-26 Univ Leland Stanford Junior LIGHT-ACTIVATED CHIMERIC OPSINES AND METHOD OF USE THEREOF
US8696722B2 (en) 2010-11-22 2014-04-15 The Board Of Trustees Of The Leland Stanford Junior University Optogenetic magnetic resonance imaging
US8716447B2 (en) 2008-11-14 2014-05-06 The Board Of Trustees Of The Leland Stanford Junior University Optically-based stimulation of target cells and modifications thereto
US8729040B2 (en) 2008-05-29 2014-05-20 The Board Of Trustees Of The Leland Stanford Junior University Cell line, system and method for optical control of secondary messengers
US8864805B2 (en) 2007-01-10 2014-10-21 The Board Of Trustees Of The Leland Stanford Junior University System for optical stimulation of target cells
US8906360B2 (en) 2005-07-22 2014-12-09 The Board Of Trustees Of The Leland Stanford Junior University Light-activated cation channel and uses thereof
US8926959B2 (en) 2005-07-22 2015-01-06 The Board Of Trustees Of The Leland Stanford Junior University System for optical stimulation of target cells
US8932562B2 (en) 2010-11-05 2015-01-13 The Board Of Trustees Of The Leland Stanford Junior University Optically controlled CNS dysfunction
US8956363B2 (en) 2008-06-17 2015-02-17 The Board Of Trustees Of The Leland Stanford Junior University Methods, systems and devices for optical stimulation of target cells using an optical transmission element
US9101759B2 (en) 2008-07-08 2015-08-11 The Board Of Trustees Of The Leland Stanford Junior University Materials and approaches for optical stimulation of the peripheral nervous system
US9238150B2 (en) 2005-07-22 2016-01-19 The Board Of Trustees Of The Leland Stanford Junior University Optical tissue interface method and apparatus for stimulating cells
US9274099B2 (en) 2005-07-22 2016-03-01 The Board Of Trustees Of The Leland Stanford Junior University Screening test drugs to identify their effects on cell membrane voltage-gated ion channel
US9284353B2 (en) 2007-03-01 2016-03-15 The Board Of Trustees Of The Leland Stanford Junior University Mammalian codon optimized nucleotide sequence that encodes a variant opsin polypeptide derived from Natromonas pharaonis (NpHR)
EP2866892A4 (en) * 2012-06-29 2016-03-23 Gen Hospital Corp EMBEDDED PHOTONIC SYSTEMS AND METHOD FOR IRRADIATING A MEDIUM THEREFOR
JP2016509487A (ja) * 2012-11-21 2016-03-31 サーキット セラピューティクス， インコーポレイテッド 光遺伝学的治療のためのシステムおよび方法
US9365628B2 (en) 2011-12-16 2016-06-14 The Board Of Trustees Of The Leland Stanford Junior University Opsin polypeptides and methods of use thereof
US9522288B2 (en) 2010-11-05 2016-12-20 The Board Of Trustees Of The Leland Stanford Junior University Upconversion of light for use in optogenetic methods
US9636380B2 (en) 2013-03-15 2017-05-02 The Board Of Trustees Of The Leland Stanford Junior University Optogenetic control of inputs to the ventral tegmental area
US9693692B2 (en) 2007-02-14 2017-07-04 The Board Of Trustees Of The Leland Stanford Junior University System, method and applications involving identification of biological circuits such as neurological characteristics
WO2018085253A1 (en) * 2016-11-01 2018-05-11 Massachusetts Institute Of Technology Transdermal optogenetic peripheral nerve stimulation
US9992981B2 (en) 2010-11-05 2018-06-12 The Board Of Trustees Of The Leland Stanford Junior University Optogenetic control of reward-related behaviors
US10035027B2 (en) 2007-10-31 2018-07-31 The Board Of Trustees Of The Leland Stanford Junior University Device and method for ultrasonic neuromodulation via stereotactic frame based technique
US10052497B2 (en) 2005-07-22 2018-08-21 The Board Of Trustees Of The Leland Stanford Junior University System for optical stimulation of target cells
US10086012B2 (en) 2010-11-05 2018-10-02 The Board Of Trustees Of The Leland Stanford Junior University Control and characterization of memory function
US10220092B2 (en) 2013-04-29 2019-03-05 The Board Of Trustees Of The Leland Stanford Junior University Devices, systems and methods for optogenetic modulation of action potentials in target cells
US10307609B2 (en) 2013-08-14 2019-06-04 The Board Of Trustees Of The Leland Stanford Junior University Compositions and methods for controlling pain
US10426970B2 (en) 2007-10-31 2019-10-01 The Board Of Trustees Of The Leland Stanford Junior University Implantable optical stimulators
US10568516B2 (en) 2015-06-22 2020-02-25 The Board Of Trustees Of The Leland Stanford Junior University Methods and devices for imaging and/or optogenetic control of light-responsive neurons
US10568307B2 (en) 2010-11-05 2020-02-25 The Board Of Trustees Of The Leland Stanford Junior University Stabilized step function opsin proteins and methods of using the same
US10711242B2 (en) 2008-06-17 2020-07-14 The Board Of Trustees Of The Leland Stanford Junior University Apparatus and methods for controlling cellular development
US10974064B2 (en) 2013-03-15 2021-04-13 The Board Of Trustees Of The Leland Stanford Junior University Optogenetic control of behavioral state
US11103723B2 (en) 2012-02-21 2021-08-31 The Board Of Trustees Of The Leland Stanford Junior University Methods for treating neurogenic disorders of the pelvic floor
US11294165B2 (en) 2017-03-30 2022-04-05 The Board Of Trustees Of The Leland Stanford Junior University Modular, electro-optical device for increasing the imaging field of view using time-sequential capture

Families Citing this family (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20150182756A1 (en) * 2005-08-05 2015-07-02 Gholam A. Peyman Methods to regulate polarization and enhance function of cells
US10022457B2 (en) * 2005-08-05 2018-07-17 Gholam A. Peyman Methods to regulate polarization and enhance function of cells
US9962558B2 (en) * 2005-08-05 2018-05-08 Gholam A. Peyman Methods to regulate polarization and enhance function of cells
CN105189697B (zh) 2013-03-15 2018-01-02 麻省理工学院 用于标记物品和组织的稀土空间/光谱微粒条码
US9365659B2 (en) * 2014-01-29 2016-06-14 Excelsior Nanotech Corporation System and method for optimizing the efficiency of photo-polymerization
CA2944056A1 (en) * 2014-03-27 2015-10-01 Circuit Therapeutics, Inc. System and method for therapeutic management of cough
JP2017511129A (ja) 2014-03-28 2017-04-20 ザ ボード オブ トラスティーズ オブ ザ レランド スタンフォード ジュニア ユニバーシティー 遺伝子操作された光活性化アニオンチャネルタンパク質及びその使用方法
KR101552446B1 (ko) * 2014-12-22 2015-09-10 성균관대학교산학협력단 무선 생체 광 자극기
US9895467B2 (en) 2015-05-14 2018-02-20 California Institute Of Technology Light adjustable intraocular lenses using upconverting nanoparticles and near infrared (NIR) light
JP2018529335A (ja) 2015-09-15 2018-10-11 ザ ボード オブ トラスティーズ オブ ザ レランド スタンフォード ジュニア ユニバーシティー 光応答性ポリペプチド及びその使用方法
WO2018218085A2 (en) 2017-05-25 2018-11-29 Prellis Biologics, Inc. Three-dimensional printed organs, devices, and matrices
WO2018200658A1 (en) * 2017-04-25 2018-11-01 Theralase Biotech Inc. Method and apparatus for photoactivating nuclear receptors
WO2019005943A1 (en) * 2017-06-28 2019-01-03 California Institute Of Technology LIGHT ADJUSTABLE INTRAOCULAR LENSES USING ASCENDING CONVERSION OF HEART-WOOD NANOPARTICLES AND INFRARED NEAR-LIGHT (NIR)
US11103725B2 (en) 2017-09-05 2021-08-31 City University Of Hong Kong Wireless optogenetic device and associated radiation system
US20190076526A1 (en) * 2017-09-13 2019-03-14 Posco Upconversion nanoparticle, hyaluronic acid-upconversion nanoparticle conjugate, and a production method thereof using a calculation from first principles
US11723579B2 (en) 2017-09-19 2023-08-15 Neuroenhancement Lab, LLC Method and apparatus for neuroenhancement
US11717686B2 (en) 2017-12-04 2023-08-08 Neuroenhancement Lab, LLC Method and apparatus for neuroenhancement to facilitate learning and performance
US12280219B2 (en) 2017-12-31 2025-04-22 NeuroLight, Inc. Method and apparatus for neuroenhancement to enhance emotional response
US11318277B2 (en) 2017-12-31 2022-05-03 Neuroenhancement Lab, LLC Method and apparatus for neuroenhancement to enhance emotional response
US11364361B2 (en) 2018-04-20 2022-06-21 Neuroenhancement Lab, LLC System and method for inducing sleep by transplanting mental states
WO2020028436A1 (en) * 2018-07-31 2020-02-06 Prellis Biologics, Inc. Optically-induced auto-encapsulation
JP2020022389A (ja) * 2018-08-07 2020-02-13 国立大学法人横浜国立大学 光細胞操作法
EP3849410A4 (en) 2018-09-14 2022-11-02 Neuroenhancement Lab, LLC System and method of improving sleep
WO2020113018A1 (en) * 2018-11-27 2020-06-04 President And Fellows Of Harvard College Photon upconversion nanocapsules for 3d printing and other applications
EP3930843A4 (en) * 2019-02-25 2023-04-05 University of Massachusetts LONG-ACTING PHOTORECEPTOR BINDING NANOPARTICLES, AND COMPOSITIONS AND METHODS THEREOF
JP2021031467A (ja) * 2019-08-28 2021-03-01 国立大学法人東海国立大学機構 オプシンの活性を調節する方法
US11921271B2 (en) 2020-05-22 2024-03-05 The Board Of Trustees Of The Leland Stanford Junior Univeristy Multifocal macroscope for large field of view imaging of dynamic specimens
WO2021247930A1 (en) * 2020-06-03 2021-12-09 Quadratic 3D, Inc. Volumetric three-dimensional printing methods including a light sheet and systems
CN112386806A (zh) * 2020-10-10 2021-02-23 深圳敬中堂科技有限公司 一种矫治视蛋白基因相关视觉疾病的光源组合及应用
CN115006730B (zh) * 2022-04-15 2023-09-01 中国科学院西安光学精密机械研究所 双通道光遗传方法、稀土基近红外纳米材料体系及其应用
CN115463251A (zh) * 2022-09-09 2022-12-13 四川大学 复合有上转换纳米颗粒的光遗传神经修复支架及制备方法

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020164577A1 (en) * 1995-06-07 2002-11-07 The Regents Of The University Of California Detection of transmembrane potentials by optical methods
US20030009103A1 (en) * 1999-06-18 2003-01-09 Rafael Yuste Optical probing of neuronal connections with fluorescent indicators
US20080176076A1 (en) * 2006-05-11 2008-07-24 University Of Victoria Innovation And Development Corporation Functionalized lanthanide rich nanoparticles and use thereof
US20080290318A1 (en) * 2005-04-26 2008-11-27 Van Veggel Franciscus C J M Production of Light from Sol-Gel Derived Thin Films Made with Lanthanide Doped Nanoparticles, and Preparation Thereof
WO2010123993A1 (en) * 2009-04-21 2010-10-28 Tuan Vo-Dinh Non-invasive energy upconversion methods and systems for in-situ photobiomodulation

Family Cites Families (291)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2968302A (en) 1956-07-20 1961-01-17 Univ Illinois Multibeam focusing irradiator
US3131690A (en) 1962-10-22 1964-05-05 American Optical Corp Fiber optics devices
US3499437A (en) 1967-03-10 1970-03-10 Ultrasonic Systems Method and apparatus for treatment of organic structures and systems thereof with ultrasonic energy
US3567847A (en) 1969-01-06 1971-03-02 Edgar E Price Electro-optical display system
US4343301A (en) 1979-10-04 1982-08-10 Robert Indech Subcutaneous neural stimulation or local tissue destruction
US4559951A (en) 1982-11-29 1985-12-24 Cardiac Pacemakers, Inc. Catheter assembly
US4616231A (en) 1984-03-26 1986-10-07 Hughes Aircraft Company Narrow-band beam steering system
FR2580277B1 (fr) 1985-04-15 1988-06-10 Oreal Nouveaux derives naphtaleniques a action retinoique, le ur procede de preparation et compositions medicamenteuse et cosmetique les contenant
US4865042A (en) 1985-08-16 1989-09-12 Hitachi, Ltd. Ultrasonic irradiation system
EP0335326B1 (en) 1988-03-28 1994-06-15 Canon Kabushiki Kaisha Ion permeable membrane and ion transport method by utilizing said membrane
US5082670A (en) 1988-12-15 1992-01-21 The Regents Of The University Of California Method of grafting genetically modified cells to treat defects, disease or damage or the central nervous system
JP2882818B2 (ja) 1989-09-08 1999-04-12 株式会社エス・エル・ティ・ジャパン レーザ光の照射装置
CA2028261C (en) 1989-10-28 1995-01-17 Won Suck Yang Non-invasive method and apparatus for measuring blood glucose concentration
US5032123A (en) 1989-12-28 1991-07-16 Cordis Corporation Laser catheter with radially divergent treatment beam
IE914102A1 (en) 1990-11-26 1992-06-03 Genetics Inst Expression of pace in host cells and methods of use thereof
US5550316A (en) 1991-01-02 1996-08-27 Fox Chase Cancer Center Transgenic animal model system for human cutaneous melanoma
US6497872B1 (en) 1991-07-08 2002-12-24 Neurospheres Holdings Ltd. Neural transplantation using proliferated multipotent neural stem cells and their progeny
US5249575A (en) 1991-10-21 1993-10-05 Adm Tronics Unlimited, Inc. Corona discharge beam thermotherapy system
SE9103752D0 (sv) 1991-12-18 1991-12-18 Astra Ab New compounds
US5670113A (en) 1991-12-20 1997-09-23 Sibia Neurosciences, Inc. Automated analysis equipment and assay method for detecting cell surface protein and/or cytoplasmic receptor function using same
US5739273A (en) 1992-02-12 1998-04-14 Yale University Transmembrane polypeptide and methods of use
US5460954A (en) 1992-04-01 1995-10-24 Cheil Foods & Chemicals, Inc. Production of human proinsulin using a novel vector system
US5330515A (en) 1992-06-17 1994-07-19 Cyberonics, Inc. Treatment of pain by vagal afferent stimulation
US5382516A (en) 1992-09-15 1995-01-17 Schleicher & Schuell, Inc. Method and devices for delivery of substrate for the detection of enzyme-linked, membrane-based binding assays
US6315772B1 (en) 1993-09-24 2001-11-13 Transmedica International, Inc. Laser assisted pharmaceutical delivery and fluid removal
US5527695A (en) 1993-01-29 1996-06-18 Purdue Research Foundation Controlled modification of eukaryotic genomes
FI954534L (fi) 1993-03-25 1995-09-25 Univ California Heterologisten polypeptiidien ilmentyminen halobakteereissa
JP3128386B2 (ja) 1993-04-07 2001-01-29 三洋電機株式会社 神経モデル素子
US5411540A (en) 1993-06-03 1995-05-02 Massachusetts Institute Of Technology Method and apparatus for preferential neuron stimulation
GB2278783A (en) 1993-06-11 1994-12-14 Daniel Shellon Gluck Method of magnetically stimulating neural cells
US6346101B1 (en) 1993-07-19 2002-02-12 Research Foundation Of City College Of New York Photon-mediated introduction of biological materials into cells and/or cellular components
US5445608A (en) 1993-08-16 1995-08-29 James C. Chen Method and apparatus for providing light-activated therapy
JPH07171162A (ja) 1993-09-07 1995-07-11 Olympus Optical Co Ltd レーザプローブ
US5470307A (en) 1994-03-16 1995-11-28 Lindall; Arnold W. Catheter system for controllably releasing a therapeutic agent at a remote tissue site
CA2187626C (en) 1994-04-13 2009-11-03 Michael G. Kaplitt Aav-mediated delivery of dna to cells of the nervous system
US6436908B1 (en) 1995-05-30 2002-08-20 Duke University Use of exogenous β-adrenergic receptor and β-adrenergic receptor kinase gene constructs to enhance myocardial function
US5495541A (en) 1994-04-19 1996-02-27 Murray; Steven C. Optical delivery device with high numerical aperture curved waveguide
US5503737A (en) 1994-07-25 1996-04-02 Ingersoll-Rand Company Air inflow restrictor for disc filters
US5807285A (en) 1994-08-18 1998-09-15 Ethicon-Endo Surgery, Inc. Medical applications of ultrasonic energy
US5520188A (en) 1994-11-02 1996-05-28 Focus Surgery Inc. Annular array transducer
US6334846B1 (en) 1995-03-31 2002-01-01 Kabushiki Kaisha Toshiba Ultrasound therapeutic apparatus
US5795581A (en) 1995-03-31 1998-08-18 Sandia Corporation Controlled release of molecular components of dendrimer/bioactive complexes
WO1996032076A1 (en) 1995-04-11 1996-10-17 Baxter Internatonal Inc. Tissue implant systems
US6480743B1 (en) 2000-04-05 2002-11-12 Neuropace, Inc. System and method for adaptive brain stimulation
US5755750A (en) 1995-11-13 1998-05-26 University Of Florida Method and apparatus for selectively inhibiting activity in nerve fibers
US5722426A (en) 1996-02-26 1998-03-03 Kolff; Jack Coronary light probe and method of use
US5703985A (en) 1996-04-29 1997-12-30 Eclipse Surgical Technologies, Inc. Optical fiber device and method for laser surgery procedures
US5898058A (en) 1996-05-20 1999-04-27 Wellman, Inc. Method of post-polymerization stabilization of high activity catalysts in continuous polyethylene terephthalate production
US5939320A (en) 1996-05-20 1999-08-17 New York University G-coupled receptors associated with macrophage-trophic HIV, and diagnostic and therapeutic uses thereof
US20040076613A1 (en) 2000-11-03 2004-04-22 Nicholas Mazarakis Vector system
US7732129B1 (en) 1998-12-01 2010-06-08 Crucell Holland B.V. Method for the production and purification of adenoviral vectors
US5741316A (en) 1996-12-02 1998-04-21 Light Sciences Limited Partnership Electromagnetic coil configurations for power transmission through tissue
US5756351A (en) 1997-01-13 1998-05-26 The Regents Of The University Of California Biomolecular optical sensors
US5782896A (en) 1997-01-29 1998-07-21 Light Sciences Limited Partnership Use of a shape memory alloy to modify the disposition of a device within an implantable medical probe
US5904659A (en) 1997-02-14 1999-05-18 Exogen, Inc. Ultrasonic treatment for wounds
US5816256A (en) 1997-04-17 1998-10-06 Bioanalytical Systems, Inc. Movement--responsive system for conducting tests on freely-moving animals
US6436708B1 (en) 1997-04-17 2002-08-20 Paola Leone Delivery system for gene therapy to the brain
US7276488B2 (en) 1997-06-04 2007-10-02 Oxford Biomedica (Uk) Limited Vector system
US5984861A (en) 1997-09-29 1999-11-16 Boston Scientific Corporation Endofluorescence imaging module for an endoscope
US6016449A (en) 1997-10-27 2000-01-18 Neuropace, Inc. System for treatment of neurological disorders
US6647296B2 (en) 1997-10-27 2003-11-11 Neuropace, Inc. Implantable apparatus for treating neurological disorders
US6597954B1 (en) 1997-10-27 2003-07-22 Neuropace, Inc. System and method for controlling epileptic seizures with spatially separated detection and stimulation electrodes
US6790652B1 (en) 1998-01-08 2004-09-14 Bioimage A/S Method and apparatus for high density format screening for bioactive molecules
US6289229B1 (en) 1998-01-20 2001-09-11 Scimed Life Systems, Inc. Readable probe array for in vivo use
DE69938898D1 (de) 1998-04-07 2008-07-24 Cytyc Corp Vorrichtungen zur lokalisierung von läsionen in festem gewebe
US6319241B1 (en) 1998-04-30 2001-11-20 Medtronic, Inc. Techniques for positioning therapy delivery elements within a spinal cord or a brain
US6108081A (en) 1998-07-20 2000-08-22 Battelle Memorial Institute Nonlinear vibrational microscopy
US6632672B2 (en) 1998-08-19 2003-10-14 The Board Of Trustees Of The Leland Stanford Junior University Methods and compositions for genomic modification
US6377842B1 (en) 1998-09-22 2002-04-23 Aurora Optics, Inc. Method for quantitative measurement of fluorescent and phosphorescent drugs within tissue utilizing a fiber optic probe
US6253109B1 (en) 1998-11-05 2001-06-26 Medtronic Inc. System for optimized brain stimulation
EP1128769A4 (en) 1998-11-06 2007-08-01 Univ Rochester METHODS FOR IMPROVING BLOOD CIRCULATION IN ISCHEMIC TISSUE
US6303362B1 (en) 1998-11-19 2001-10-16 The Board Of Trustees Of The Leland Stanford Junior University Adenoviral vector and methods for making and using the same
US6790657B1 (en) 1999-01-07 2004-09-14 The United States Of America As Represented By The Department Of Health And Human Services Lentivirus vector system
US7507545B2 (en) 1999-03-31 2009-03-24 Cardiome Pharma Corp. Ion channel modulating activity method
US6224566B1 (en) 1999-05-04 2001-05-01 Cardiodyne, Inc. Method and devices for creating a trap for confining therapeutic drugs and/or genes in the myocardium
US6161045A (en) 1999-06-01 2000-12-12 Neuropace, Inc. Method for determining stimulation parameters for the treatment of epileptic seizures
US7655423B2 (en) 1999-06-14 2010-02-02 Henry Ford Health System Nitric oxide donors for inducing neurogenesis
US7674463B1 (en) 1999-07-15 2010-03-09 Research Development Foundation Method of inhibiting angiogenesis by administration of a corticotropin releasing factor receptor 2 agonist
US20040034882A1 (en) 1999-07-15 2004-02-19 Vale Wylie W. Corticotropin releasing factor receptor 2 deficient mice and uses thereof
EP1207788A4 (en) 1999-07-19 2009-12-09 St Jude Medical Atrial Fibrill DEVICE AND METHOD FOR THE ABLATION OF TISSUE
ES2152900B1 (es) 1999-07-23 2001-08-16 Palleja Xavier Estivill Ratones transgenicos y modelo de sobreexpresion del gen ntrk3 (trkc) basado en los mismos para el estudio y monitorizacion de tratamientos de la ansiedad, depresion y enfermedades psiquiatricas relacionadas.
KR100630292B1 (ko) 1999-08-06 2006-09-29 알프스 덴키 가부시키가이샤 자기 디스크용 자기헤드를 반송하기 위한 트레이
GB9923558D0 (en) 1999-10-05 1999-12-08 Oxford Biomedica Ltd Producer cell
GB9928248D0 (en) 1999-12-01 2000-01-26 Gill Steven S An implantable guide tube for neurosurgery
ATE291737T1 (de) 2000-01-14 2005-04-15 Migenix Corp Screening-assays unter verwendung von intramitochondrialem kalzium
US6595934B1 (en) 2000-01-19 2003-07-22 Medtronic Xomed, Inc. Methods of skin rejuvenation using high intensity focused ultrasound to form an ablated tissue area containing a plurality of lesions
US7706882B2 (en) 2000-01-19 2010-04-27 Medtronic, Inc. Methods of using high intensity focused ultrasound to form an ablated tissue area
ATE490338T1 (de) 2000-02-18 2010-12-15 Univ Leland Stanford Junior Veränderte rekombinasen zur modifizierung des genoms
US6473639B1 (en) 2000-03-02 2002-10-29 Neuropace, Inc. Neurological event detection procedure using processed display channel based algorithms and devices incorporating these procedures
JP2003531609A (ja) 2000-05-01 2003-10-28 ノバルティス アクチエンゲゼルシャフト 目に関する形質導入用ベクターおよび遺伝子治療を目的とするその用途
US6599281B1 (en) 2000-05-03 2003-07-29 Aspect Medical Systems, Inc. System and method for adaptive drug delivery
US7250294B2 (en) 2000-05-17 2007-07-31 Geron Corporation Screening small molecule drugs using neural cells differentiated from human embryonic stem cells
US6551346B2 (en) 2000-05-17 2003-04-22 Kent Crossley Method and apparatus to prevent infections
AU2001268149B2 (en) 2000-06-01 2005-08-18 University Of North Carolina At Chapel Hill Methods and compounds for controlled release of recombinant parvovirus vectors
EP1307551A2 (en) 2000-07-05 2003-05-07 PHARMACIA & UPJOHN COMPANY Human ion channels
US6686193B2 (en) 2000-07-10 2004-02-03 Vertex Pharmaceuticals, Inc. High throughput method and system for screening candidate compounds for activity against target ion channels
WO2002013906A1 (en) 2000-08-16 2002-02-21 Vanderbilt University Methods and devices for optical stimulation of neural tissues
US6567690B2 (en) 2000-10-16 2003-05-20 Cole Giller Method and apparatus for probe localization in brain matter
US7350522B2 (en) 2000-10-17 2008-04-01 Sony Corporation Scanning method for applying ultrasonic acoustic data to the human neural cortex
US6536440B1 (en) 2000-10-17 2003-03-25 Sony Corporation Method and system for generating sensory data onto the human neural cortex
US6584357B1 (en) 2000-10-17 2003-06-24 Sony Corporation Method and system for forming an acoustic signal from neural timing difference data
US20020106327A1 (en) 2000-11-15 2002-08-08 Brian Storrie B/b-like fragment targeting for the purposes of photodynamic therapy and medical imaging
US6506154B1 (en) 2000-11-28 2003-01-14 Insightec-Txsonics, Ltd. Systems and methods for controlling a phased array focused ultrasound system
SE525540C2 (sv) 2000-11-30 2005-03-08 Datainnovation I Lund Ab System och förfarande för automatisk provtagning från ett provobjekt
US20070196838A1 (en) 2000-12-08 2007-08-23 Invitrogen Corporation Methods and compositions for synthesis of nucleic acid molecules using multiple recognition sites
US6489115B2 (en) 2000-12-21 2002-12-03 The Board Of Regents Of The University Of Nebraska Genetic assays for trinucleotide repeat mutations in eukaryotic cells
US6615080B1 (en) 2001-03-29 2003-09-02 John Duncan Unsworth Neuromuscular electrical stimulation of the foot muscles for prevention of deep vein thrombosis and pulmonary embolism
US7047078B2 (en) 2001-03-30 2006-05-16 Case Western Reserve University Methods for stimulating components in, on, or near the pudendal nerve or its branches to achieve selective physiologic responses
AU2002303283A1 (en) 2001-04-04 2002-10-21 Irm Llc Methods for treating drug addiction
US7107996B2 (en) 2001-04-10 2006-09-19 Ganz Robert A Apparatus and method for treating atherosclerotic vascular disease through light sterilization
US6961045B2 (en) 2001-06-16 2005-11-01 Che-Chih Tsao Pattern projection techniques for volumetric 3D displays and 2D displays
US6810285B2 (en) 2001-06-28 2004-10-26 Neuropace, Inc. Seizure sensing and detection using an implantable device
US7144733B2 (en) 2001-08-16 2006-12-05 Sloan-Kettering Institute For Cancer Research Bio-synthetic photostimulators and methods of use
WO2003018777A1 (en) 2001-08-23 2003-03-06 The Regents Of The University Of California A universal light-switchable gene promoter system
US6974448B2 (en) 2001-08-30 2005-12-13 Medtronic, Inc. Method for convection enhanced delivery catheter to treat brain and other tumors
US7904176B2 (en) 2006-09-07 2011-03-08 Bio Control Medical (B.C.M.) Ltd. Techniques for reducing pain associated with nerve stimulation
WO2003020103A2 (en) 2001-09-04 2003-03-13 Amit Technology Science & Medicine Ltd. Method of and device for therapeutic illumination of internal organs and tissues
EP1496860A1 (en) 2001-09-28 2005-01-19 Saoirse Corporation Localized non-invasive biological modulation system
US7175596B2 (en) 2001-10-29 2007-02-13 Insightec-Txsonics Ltd System and method for sensing and locating disturbances in an energy path of a focused ultrasound system
US7303578B2 (en) 2001-11-01 2007-12-04 Photothera, Inc. Device and method for providing phototherapy to the brain
US8308784B2 (en) 2006-08-24 2012-11-13 Jackson Streeter Low level light therapy for enhancement of neurologic function of a patient affected by Parkinson's disease
AU2002363478A1 (en) 2001-11-08 2003-05-19 Children's Medical Center Corporation Bacterial ion channel and a method for screening ion channel modulators
CA2465337A1 (en) 2001-11-14 2003-05-22 Yamanouchi Pharmaceutical Co., Ltd. Transgenic animal
MXPA04005010A (es) 2001-11-26 2005-04-08 Advanced Cell Tech Inc METODO PARA HACER Y USAR NUCLEOS CELULARES SOMáTICOS METODOS PARA HACER Y USAR NUCLEOS CELULARES SOMáTICOS HUMANOS REPROGRAMADOS Y CELULAS DEL TALLO HUMANAS AUTOLOGAS E ISOGENICAS.
US20030104512A1 (en) 2001-11-30 2003-06-05 Freeman Alex R. Biosensors for single cell and multi cell analysis
US6873868B2 (en) 2001-12-31 2005-03-29 Infraredx, Inc. Multi-fiber catheter probe arrangement for tissue analysis or treatment
US6721603B2 (en) 2002-01-25 2004-04-13 Cyberonics, Inc. Nerve stimulation as a treatment for pain
US6666857B2 (en) 2002-01-29 2003-12-23 Robert F. Smith Integrated wavefront-directed topography-controlled photoablation
JP2005516684A (ja) 2002-02-01 2005-06-09 ザ クリーブランド クリニック ファウンデイション マイクロ注入装置
EP1476080A4 (en) 2002-02-20 2010-06-02 Medicis Technologies Corp ULTRASOUND TREATMENT AND COMPOSITE EXPLANATION OF FAT FABRICS
JP4363843B2 (ja) 2002-03-08 2009-11-11 オリンパス株式会社 カプセル型内視鏡
US20030186249A1 (en) 2002-04-01 2003-10-02 Zairen Sun Human TARPP genes and polypeptides
US20070135875A1 (en) 2002-04-08 2007-06-14 Ardian, Inc. Methods and apparatus for thermally-induced renal neuromodulation
DE10216005A1 (de) 2002-04-11 2003-10-30 Max Planck Gesellschaft Verwendung von biologischen Photorezeptoren als direkt lichtgesteuerte Ionenkanäle
US9592409B2 (en) 2002-04-30 2017-03-14 The Regents Of The University Of California Methods for modifying electrical currents in neuronal circuits
US7283861B2 (en) 2002-04-30 2007-10-16 Alexander Bystritsky Methods for modifying electrical currents in neuronal circuits
AU2003224374A1 (en) 2002-05-13 2003-11-11 Koninklijke Philips Electronics N.V. Reduction of susceptibility artifacts in subencoded single-shot magnetic resonance imaging
JP2006511197A (ja) 2002-05-31 2006-04-06 スローン − ケッタリング インスティチュート フォー キャンサー リサーチ 異種刺激依存性イオンチャンネル及びその使用方法
EP1513584A2 (en) 2002-06-04 2005-03-16 Cyberkinetics, Inc. Optically-connected implants and related systems and methods of use
US7292890B2 (en) 2002-06-20 2007-11-06 Advanced Bionics Corporation Vagus nerve stimulation via unidirectional propagation of action potentials
US20040049134A1 (en) 2002-07-02 2004-03-11 Tosaya Carol A. System and methods for treatment of alzheimer's and other deposition-related disorders of the brain
US20050020945A1 (en) 2002-07-02 2005-01-27 Tosaya Carol A. Acoustically-aided cerebrospinal-fluid manipulation for neurodegenerative disease therapy
WO2004021243A2 (de) 2002-08-09 2004-03-11 Siemens Aktiengesellschaft Verfahren sowie computerprogramm mit programmcode-mitteln und computerprogramm-produkt zur analyse einer wirksamkeit eines pharmazeutischen präparats
AU2003265509A1 (en) 2002-08-19 2004-03-03 Arizona Board Regents Neurostimulator
US20060014206A1 (en) 2002-10-10 2006-01-19 Menghang Xia Assay methods for state-dependent calcium channel agonists/antagonists
US7355033B2 (en) 2002-11-18 2008-04-08 Health Research, Inc. Screening for West Nile Virus antiviral therapy
AU2003297023A1 (en) 2002-12-16 2004-07-29 Genentech, Inc. Transgenic mice expressing human cd20
US20040122475A1 (en) 2002-12-18 2004-06-24 Myrick Andrew J. Electrochemical neuron systems
EP1601965A4 (en) 2003-03-12 2010-11-10 Samaritan Pharmaceuticals Inc SIMULATION OF NEUROLOGICAL DISEASES WITH ANIMAL MODEL
US20040216177A1 (en) 2003-04-25 2004-10-28 Otsuka Pharmaceutical Co., Ltd. Congenic rats containing a mutant GPR10 gene
US7377900B2 (en) 2003-06-02 2008-05-27 Insightec - Image Guided Treatment Ltd. Endo-cavity focused ultrasound transducer
US7442685B2 (en) 2003-06-13 2008-10-28 The University Of North Carolina At Chapel Hill DOT1 histone methyltransferases as a target for identifying therapeutic agents for leukemia
CA2432810A1 (en) 2003-06-19 2004-12-19 Andres M. Lozano Method of treating depression, mood disorders and anxiety disorders by brian infusion
US7091500B2 (en) 2003-06-20 2006-08-15 Lucent Technologies Inc. Multi-photon endoscopic imaging system
WO2005007233A2 (en) 2003-06-20 2005-01-27 Massachusetts Institute Of Technology Application of electrical stimulation for functional tissue engineering in vitro and in vivo
JP2005034073A (ja) 2003-07-16 2005-02-10 Masamitsu Iino ミオシン軽鎖リン酸化の測定用蛍光性プローブ
US20050153885A1 (en) 2003-10-08 2005-07-14 Yun Anthony J. Treatment of conditions through modulation of the autonomic nervous system
US7548775B2 (en) 2003-10-21 2009-06-16 The Regents Of The University Of Michigan Intracranial neural interface system
US6952097B2 (en) 2003-10-22 2005-10-04 Siemens Aktiengesellschaft Method for slice position planning of tomographic measurements, using statistical images
US20060034943A1 (en) 2003-10-31 2006-02-16 Technology Innovations Llc Process for treating a biological organism
US20080119421A1 (en) 2003-10-31 2008-05-22 Jack Tuszynski Process for treating a biological organism
EP1701772A4 (en) 2003-11-21 2012-03-28 Univ Johns Hopkins BIOMOLECOLE PARTITIONING MOTIVES AND USES THEREOF
US20050124897A1 (en) 2003-12-03 2005-06-09 Scimed Life Systems, Inc. Apparatus and methods for delivering acoustic energy to body tissue
US7783349B2 (en) 2006-04-10 2010-08-24 Cardiac Pacemakers, Inc. System and method for closed-loop neural stimulation
CN1236305C (zh) * 2004-02-03 2006-01-11 复旦大学 生物光敏蛋白－纳米半导体复合光电极的制备方法
US7662114B2 (en) 2004-03-02 2010-02-16 Focus Surgery, Inc. Ultrasound phased arrays
US20050215764A1 (en) 2004-03-24 2005-09-29 Tuszynski Jack A Biological polymer with differently charged portions
ITMI20040598A1 (it) 2004-03-26 2004-06-26 Carlotta Giorgi Metodo per la rilevazione di parametri intracellulari con sonde proteiche luminescenti per lo screening di molecole in grado di alterare detti parametri
US8512219B2 (en) 2004-04-19 2013-08-20 The Invention Science Fund I, Llc Bioelectromagnetic interface system
WO2005107858A1 (en) 2004-04-30 2005-11-17 Advanced Neuromodulation Systems, Inc. Method of treating mood disorders and/or anxiety disorders by brain stimulation
US7670838B2 (en) 2004-05-24 2010-03-02 The Board Of Trustees Of The Leland Stanford Junior University Coupling of excitation and neurogenesis in neural stem/progenitor cells
US20050279354A1 (en) 2004-06-21 2005-12-22 Harvey Deutsch Structures and Methods for the Joint Delivery of Fluids and Light
US20060057614A1 (en) 2004-08-04 2006-03-16 Nathaniel Heintz Tethering neuropeptides and toxins for modulation of ion channels and receptors
US7699780B2 (en) 2004-08-11 2010-04-20 Insightec—Image-Guided Treatment Ltd. Focused ultrasound system with adaptive anatomical aperture shaping
US8409099B2 (en) 2004-08-26 2013-04-02 Insightec Ltd. Focused ultrasound system for surrounding a body tissue mass and treatment method
US8821559B2 (en) 2004-08-27 2014-09-02 Codman & Shurtleff, Inc. Light-based implants for treating Alzheimer's disease
EP1827580A1 (en) 2004-10-21 2007-09-05 Advanced Neuromodulation Systems, Inc. New stimulation design for neuromodulation
US7544171B2 (en) 2004-10-22 2009-06-09 General Patent Llc Methods for promoting nerve regeneration and neuronal growth and elongation
US7833257B2 (en) 2004-11-12 2010-11-16 Northwestern University Apparatus and methods for optical stimulation of the auditory nerve
JP2008520280A (ja) 2004-11-15 2008-06-19 デチャームス，クリストファー 光を使用した神経組織の刺激の適用
US8109981B2 (en) 2005-01-25 2012-02-07 Valam Corporation Optical therapies and devices
US7686839B2 (en) 2005-01-26 2010-03-30 Lumitex, Inc. Phototherapy treatment devices for applying area lighting to a wound
US9034650B2 (en) 2005-02-02 2015-05-19 Intrexon Corporation Site-specific serine recombinases and methods of their use
US7553284B2 (en) 2005-02-02 2009-06-30 Vaitekunas Jeffrey J Focused ultrasound for pain reduction
JP2006217866A (ja) 2005-02-10 2006-08-24 Tohoku Univ 光感受性を新たに賦与した神経細胞
US7548780B2 (en) 2005-02-22 2009-06-16 Cardiac Pacemakers, Inc. Cell therapy and neural stimulation for cardiac repair
US7288108B2 (en) 2005-03-14 2007-10-30 Codman & Shurtleff, Inc. Red light implant for treating Parkinson's disease
US20070059775A1 (en) * 2005-03-29 2007-03-15 The Trustees Of Columbia University In The City Of New York Synthesis and conjugation of iron oxide nanoparticles to antibodies for targeting specific cells using fluorescence and MR imaging techniques
ES2668959T3 (es) 2005-03-31 2018-05-23 Esther Mayer Dispositivo de sonda para la fotobiomodulación del tejido que reviste una cavidad corporal
JP2006295350A (ja) 2005-04-07 2006-10-26 Sony Corp 撮像装置及び撮像結果の処理方法
US9445211B2 (en) 2005-04-11 2016-09-13 St. Jude Medical, Atrial Fibrillation Division, Inc. Methods for manufacturing high intensity ultrasound transducers
GB0508254D0 (en) 2005-04-23 2005-06-01 Smith & Nephew Ultrasound device
US7640057B2 (en) 2005-04-25 2009-12-29 Cardiac Pacemakers, Inc. Methods of providing neural markers for sensed autonomic nervous system activity
JP5766389B2 (ja) 2005-05-02 2015-08-19 ジェンザイム・コーポレーション 脊髄疾患の遺伝子療法
CN1879906A (zh) 2005-06-15 2006-12-20 郑云峰 中枢神经系统磁刺激装置及其使用方法
US20070027443A1 (en) 2005-06-29 2007-02-01 Ondine International, Ltd. Hand piece for the delivery of light and system employing the hand piece
US20090093403A1 (en) 2007-03-01 2009-04-09 Feng Zhang Systems, methods and compositions for optical stimulation of target cells
WO2007024391A2 (en) 2005-07-22 2007-03-01 The Board Of Trustees Of The Leland Stanford Junior University Light-activated cation channel and uses thereof
US10052497B2 (en) 2005-07-22 2018-08-21 The Board Of Trustees Of The Leland Stanford Junior University System for optical stimulation of target cells
US9274099B2 (en) 2005-07-22 2016-03-01 The Board Of Trustees Of The Leland Stanford Junior University Screening test drugs to identify their effects on cell membrane voltage-gated ion channel
US8926959B2 (en) 2005-07-22 2015-01-06 The Board Of Trustees Of The Leland Stanford Junior University System for optical stimulation of target cells
US9238150B2 (en) 2005-07-22 2016-01-19 The Board Of Trustees Of The Leland Stanford Junior University Optical tissue interface method and apparatus for stimulating cells
US7736382B2 (en) 2005-09-09 2010-06-15 Lockheed Martin Corporation Apparatus for optical stimulation of nerves and other animal tissue
US8852184B2 (en) 2005-09-15 2014-10-07 Cannuflow, Inc. Arthroscopic surgical temperature control system
US20080077200A1 (en) 2006-09-21 2008-03-27 Aculight Corporation Apparatus and method for stimulation of nerves and automated control of surgical instruments
US8058509B2 (en) 2005-12-21 2011-11-15 Pioneer Hi-Bred International, Inc. Methods and compositions for in planta production of inverted repeats
US7610100B2 (en) 2005-12-30 2009-10-27 Boston Scientific Neuromodulation Corporation Methods and systems for treating osteoarthritis
US20070191906A1 (en) 2006-02-13 2007-08-16 Anand Iyer Method and apparatus for selective nerve stimulation
US20070219600A1 (en) 2006-03-17 2007-09-20 Michael Gertner Devices and methods for targeted nasal phototherapy
US20070282404A1 (en) 2006-04-10 2007-12-06 University Of Rochester Side-firing linear optic array for interstitial optical therapy and monitoring using compact helical geometry
US20070253995A1 (en) 2006-04-28 2007-11-01 Medtronic, Inc. Drug Delivery Methods and Devices for Treating Stress Urinary Incontinence
US8057464B2 (en) 2006-05-03 2011-11-15 Light Sciences Oncology, Inc. Light transmission system for photoreactive therapy
JP2009536219A (ja) 2006-05-04 2009-10-08 ウェイン・ステート・ユニバーシティー ロドプシン拡散のインビボ送達による視覚応答の回復
US20080262411A1 (en) 2006-06-02 2008-10-23 Dobak John D Dynamic nerve stimulation in combination with other eating disorder treatment modalities
CN101500644A (zh) 2006-06-19 2009-08-05 高地仪器公司 用于刺激生物组织的设备和方法
US7795632B2 (en) 2006-06-26 2010-09-14 Osram Sylvania Inc. Light emitting diode with direct view optic
US20080027505A1 (en) 2006-07-26 2008-01-31 G&L Consulting, Llc System and method for treatment of headaches
WO2008014382A2 (en) 2006-07-26 2008-01-31 Case Western Reserve University System and method for controlling g-protein coupled receptor pathways
SG139588A1 (en) 2006-07-28 2008-02-29 St Microelectronics Asia Addressable led architecure
US7848797B2 (en) 2006-08-17 2010-12-07 Neurometrix, Inc. Motor unit number estimation (MUNE) for the assessment of neuromuscular function
US7521590B2 (en) 2006-09-01 2009-04-21 Korea Institute Of Science And Technology Phospholipase C β1 (PLCβ1) knockout mice as a model system for testing schizophrenia drugs
US10420948B2 (en) 2006-10-30 2019-09-24 Medtronic, Inc. Implantable medical device with variable data retransmission characteristics based upon data type
WO2008070765A2 (en) 2006-12-06 2008-06-12 Case Western Reserve University Light-sensitive constructs for inducing cell death and cell signaling
EE200600039A (et) 2006-12-12 2008-10-15 Tartu Ülikool Transgeenne loommudel patoloogilise ärevuse modelleerimiseks, meetod patoloogilisest ärevusest p?hjustatud haiguste v?i seisundite ravimiseks sobilike ühendite tuvastamiseks ja meetod Wfs1 valgu kasutamiseks sihtmärgina patoloogilise ärevuse vastase
WO2008086470A1 (en) 2007-01-10 2008-07-17 The Board Of Trustees Of The Leland Stanford Junior University System for optical stimulation of target cells
US7883536B1 (en) 2007-01-19 2011-02-08 Lockheed Martin Corporation Hybrid optical-electrical probes
US8401609B2 (en) 2007-02-14 2013-03-19 The Board Of Trustees Of The Leland Stanford Junior University System, method and applications involving identification of biological circuits such as neurological characteristics
US8282559B2 (en) 2007-03-09 2012-10-09 Philip Chidi Njemanze Method for inducing and monitoring long-term potentiation and long-term depression using transcranial doppler ultrasound device in head-down bed rest
US8139339B2 (en) 2007-03-16 2012-03-20 Old Dominion University Research Foundation Modulation of neuromuscular functions with ultrashort electrical pulses
US20080287821A1 (en) 2007-03-30 2008-11-20 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Computational user-health testing
CN101288768A (zh) 2007-04-20 2008-10-22 中央研究院 用于治疗渐进神经退化症的医药组合物
JP5361868B2 (ja) 2007-05-01 2013-12-04 ニューロフォーカス・インコーポレーテッド 神経情報貯蔵システム
US20110165681A1 (en) 2009-02-26 2011-07-07 Massachusetts Institute Of Technology Light-Activated Proton Pumps and Applications Thereof
US8097422B2 (en) 2007-06-20 2012-01-17 Salk Institute For Biological Studies Kir channel modulators
US9138596B2 (en) 2007-08-22 2015-09-22 Cardiac Pacemakers, Inc. Optical depolarization of cardiac tissue
US10434327B2 (en) 2007-10-31 2019-10-08 The Board Of Trustees Of The Leland Stanford Junior University Implantable optical stimulators
US10035027B2 (en) 2007-10-31 2018-07-31 The Board Of Trustees Of The Leland Stanford Junior University Device and method for ultrasonic neuromodulation via stereotactic frame based technique
DE112008003192T5 (de) 2007-11-26 2010-10-07 Micro-Transponder, Inc., Dallas Übertragungsspulenarchitektur
US8562658B2 (en) 2007-12-06 2013-10-22 Technion Research & Development Foundation Limited Method and system for optical stimulation of neurons
US8883719B2 (en) 2008-01-16 2014-11-11 University Of Connecticut Bacteriorhodopsin protein variants and methods of use for long term data storage
US20090254134A1 (en) 2008-02-04 2009-10-08 Medtrode Inc. Hybrid ultrasound/electrode device for neural stimulation and recording
WO2009119782A1 (ja) 2008-03-24 2009-10-01 国立大学法人東北大学 改変された光受容体チャネル型ロドプシンタンパク質
CA3095369C (en) 2008-04-04 2023-09-26 Immunolight, Llc Non-invasive systems and methods for in-situ photobiomodulation
MX2010011657A (es) 2008-04-23 2011-01-21 Univ Leland Stanford Junior Sistemas, metodos y composiciones para la estimulacion optica de celulas objetivo.
EP2910637A1 (en) 2008-05-20 2015-08-26 University of Florida Research Foundation, Inc. Vectors for delivery of light-sensitive proteins and methods of use
MY152003A (en) 2008-05-29 2014-08-15 Univ Leland Stanford Junior Cell line, system and method for optical control of secondary messengers
US8636653B2 (en) 2008-06-09 2014-01-28 Capso Vision, Inc. In vivo camera with multiple sources to illuminate tissue at different distances
SG191593A1 (en) 2008-06-17 2013-07-31 Univ Leland Stanford Junior Methods, systems and devices for optical stimulation of target cells using an optical transmission element
BRPI0915583A2 (pt) 2008-06-17 2016-01-26 Univ Leland Stanford Junior aparelho e métodos para controle do desenvolvimento celular
WO2010006049A1 (en) 2008-07-08 2010-01-14 The Board Of Trustees Of The Leland Stanford Junior University Materials and approaches for optical stimulation of the peripheral nervous system
US8770203B2 (en) * 2008-07-14 2014-07-08 Immunolight, Llc. Advanced methods and systems for treating cell proliferation disorders
CA2738652A1 (en) 2008-09-25 2010-04-01 The Trustees Of Columbia University In The City Of New York Device, apparatus and method for providing photostimulation and imaging of structures
NZ602416A (en) 2008-11-14 2014-08-29 Univ Leland Stanford Junior Optically-based stimulation of target cells and modifications thereto
US8878760B2 (en) 2008-11-26 2014-11-04 Sharp Kabushiki Kaisha Liquid crystal display device, method for driving liquid crystal display device, and television receiver
WO2010111358A2 (en) 2009-03-24 2010-09-30 Spinal Modulation, Inc. Pain management with stimulation subthreshold to parasthesia
KR101081360B1 (ko) * 2009-03-25 2011-11-08 한국과학기술연구원 어레이형 광 자극 장치
WO2011005978A2 (en) 2009-07-08 2011-01-13 Duke University Methods of manipulating cell signaling
US20110112463A1 (en) 2009-11-12 2011-05-12 Jerry Silver Compositions and methods for treating a neuronal injury or neuronal disorders
US8936630B2 (en) 2009-11-25 2015-01-20 Medtronic, Inc. Optical stimulation therapy
EP2539015B1 (en) 2010-02-26 2015-12-30 Cornell University Retina prosthesis
ES2676274T3 (es) 2010-03-17 2018-07-18 The Board Of Trustees Of The Leland Stanford Junior University Moléculas sensibles a la luz que permiten el paso de iones
GB2492719A (en) 2010-04-05 2013-01-09 Eos Neuroscience Inc Methods and compositions for decreasing chronic pain
US10051240B2 (en) 2010-06-14 2018-08-14 Howard Hughes Medical Institute Structured plane illumination microscopy
CN103168236B (zh) 2010-08-23 2016-01-20 哈佛大学管理委员会 用于膜电位测定的光遗传学探针
HRP20150846T1 (hr) 2010-09-08 2015-09-11 MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. Mutirani kalanski rodopsin 2
CN106947741A (zh) 2010-11-05 2017-07-14 斯坦福大学托管董事会 光活化嵌合视蛋白及其使用方法
AU2011323237B2 (en) 2010-11-05 2015-11-12 The Board Of Trustees Of The Leland Stanford Junior University Optically-controlled CNS dysfunction
WO2012061681A1 (en) 2010-11-05 2012-05-10 The Board Of Trustees Of The Leland Stanford Junior University. Control and characterization of memory function
AU2011323197B2 (en) 2010-11-05 2015-11-19 The Board Of Trustees Of The Leland Stanford Junior University Control and characterization of psychotic states
EP2635341B1 (en) 2010-11-05 2018-08-08 The Board of Trustees of the Leland Stanford Junior University Upconversion of light for use in optogenetic methods
CA2816990A1 (en) 2010-11-05 2012-05-10 The Board Of Trustees Of The Leland Stanford Junior University Stabilized step function opsin proteins and methods of using the same
WO2012061688A1 (en) 2010-11-05 2012-05-10 The Board Of Trustees Of The Leland Stanford Junior University Optogenetic control of reward-related behaviors
US8957028B2 (en) 2010-11-13 2015-02-17 Massachusetts Institute Of Technology Red-shifted opsin molecules and uses thereof
US8696722B2 (en) 2010-11-22 2014-04-15 The Board Of Trustees Of The Leland Stanford Junior University Optogenetic magnetic resonance imaging
WO2012106407A2 (en) 2011-02-01 2012-08-09 The University Of Vermont And State Agricultural College Diagnostic and therapeutic methods and products related to anxiety disorders
US20120253261A1 (en) 2011-03-29 2012-10-04 Medtronic, Inc. Systems and methods for optogenetic modulation of cells within a patient
CA2839938A1 (en) 2011-06-28 2013-01-03 University Of Rochester Photoactivatable receptors and their uses
US9782091B2 (en) 2011-07-25 2017-10-10 Neuronexus Technologies, Inc. Opto-electrical device for artifact reduction
KR102023754B1 (ko) 2011-07-27 2019-09-20 더 보오드 오브 트러스티스 오브 더 유니버시티 오브 일리노이즈 생체분자 특성규명용 나노포어 센서
CA3036859A1 (en) 2011-12-16 2013-06-20 The Board Of Trustees Of The Leland Stanford Junior University Opsin polypeptides and methods of use thereof
US20140024701A1 (en) 2012-02-21 2014-01-23 Circuit Therapeutics, Inc. Compositions and Methods for Treating Neurogenic Disorders of the Pelvic Floor
EP2817670B1 (en) 2012-02-23 2020-07-29 The United States Of America, As Represented By The Sectretary, Department Of Health And Human Services Multi-focal structured illumination microscopy systems and methods
CN104270942B (zh) 2012-03-20 2018-02-02 斯坦福大学托管董事会 非人类动物抑郁症模型及其使用方法
EP3659518A1 (en) 2012-11-21 2020-06-03 Circuit Therapeutics, Inc. System and method for optogenetic therapy
JP2016507078A (ja) 2013-01-25 2016-03-07 ザ トラスティーズ オブ コロンビア ユニバーシティ イン ザ シティオブ ニューヨーク 被写界深度３ｄイメージングｓｌｍ顕微鏡
CA2906756A1 (en) 2013-03-15 2014-09-18 The Board Of Trustees Of The Leland Stanford Junior University Optogenetic control of behavioral state
US9636380B2 (en) 2013-03-15 2017-05-02 The Board Of Trustees Of The Leland Stanford Junior University Optogenetic control of inputs to the ventral tegmental area
EP2991491B1 (en) 2013-04-29 2019-12-25 The Board of Trustees of the Leland Stanford Junior University Devices, systems and methods for optogenetic modulation of action potentials in target cells
US20150112411A1 (en) 2013-10-18 2015-04-23 Varaya Photoceuticals, Llc High powered light emitting diode photobiology compositions, methods and systems
WO2016019075A1 (en) 2014-07-29 2016-02-04 Circuit Therapeutics, Inc. System and method for optogenetic therapy
AU2014411185B2 (en) 2014-11-11 2017-10-26 Guangdong Oppo Mobile Telecommunications Corp., Ltd. Power adaptor, terminal and charging system

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020164577A1 (en) * 1995-06-07 2002-11-07 The Regents Of The University Of California Detection of transmembrane potentials by optical methods
US20030009103A1 (en) * 1999-06-18 2003-01-09 Rafael Yuste Optical probing of neuronal connections with fluorescent indicators
US20080290318A1 (en) * 2005-04-26 2008-11-27 Van Veggel Franciscus C J M Production of Light from Sol-Gel Derived Thin Films Made with Lanthanide Doped Nanoparticles, and Preparation Thereof
US20080176076A1 (en) * 2006-05-11 2008-07-24 University Of Victoria Innovation And Development Corporation Functionalized lanthanide rich nanoparticles and use thereof
US20110021970A1 (en) * 2007-11-06 2011-01-27 Duke University Non-invasive energy upconversion methods and systems for in-situ photobiomodulation
WO2010123993A1 (en) * 2009-04-21 2010-10-28 Tuan Vo-Dinh Non-invasive energy upconversion methods and systems for in-situ photobiomodulation

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP2635341A4 *

Cited By (104)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10451608B2 (en) 2005-07-22 2019-10-22 The Board Of Trustees Of The Leland Stanford Junior University Cell line, system and method for optical-based screening of ion-channel modulators
US9101690B2 (en) 2005-07-22 2015-08-11 The Board Of Trustees Of The Leland Stanford Junior University Light-activated cation channel and uses thereof
US10422803B2 (en) 2005-07-22 2019-09-24 The Board Of Trustees Of The Leland Stanford Junior University Light-activated cation channel and uses thereof
US9360472B2 (en) 2005-07-22 2016-06-07 The Board Of Trustees Of The Leland Stanford Junior University Cell line, system and method for optical-based screening of ion-channel modulators
US10036758B2 (en) 2005-07-22 2018-07-31 The Board Of Trustees Of The Leland Stanford Junior University Delivery of a light-activated cation channel into the brain of a subject
US10094840B2 (en) 2005-07-22 2018-10-09 The Board Of Trustees Of The Leland Stanford Junior University Light-activated cation channel and uses thereof
US10052497B2 (en) 2005-07-22 2018-08-21 The Board Of Trustees Of The Leland Stanford Junior University System for optical stimulation of target cells
US10627410B2 (en) 2005-07-22 2020-04-21 The Board Of Trustees Of The Leland Stanford Junior University Light-activated cation channel and uses thereof
US9278159B2 (en) 2005-07-22 2016-03-08 The Board Of Trustees Of The Leland Stanford Junior University Light-activated cation channel and uses thereof
US9238150B2 (en) 2005-07-22 2016-01-19 The Board Of Trustees Of The Leland Stanford Junior University Optical tissue interface method and apparatus for stimulating cells
US8926959B2 (en) 2005-07-22 2015-01-06 The Board Of Trustees Of The Leland Stanford Junior University System for optical stimulation of target cells
US9274099B2 (en) 2005-07-22 2016-03-01 The Board Of Trustees Of The Leland Stanford Junior University Screening test drugs to identify their effects on cell membrane voltage-gated ion channel
US10569099B2 (en) 2005-07-22 2020-02-25 The Board Of Trustees Of The Leland Stanford Junior University System for optical stimulation of target cells
US8906360B2 (en) 2005-07-22 2014-12-09 The Board Of Trustees Of The Leland Stanford Junior University Light-activated cation channel and uses thereof
US9829492B2 (en) 2005-07-22 2017-11-28 The Board Of Trustees Of The Leland Stanford Junior University Implantable prosthetic device comprising a cell expressing a channelrhodopsin
US10046174B2 (en) 2005-07-22 2018-08-14 The Board Of Trustees Of The Leland Stanford Junior University System for electrically stimulating target neuronal cells of a living animal in vivo
US9187745B2 (en) 2007-01-10 2015-11-17 The Board Of Trustees Of The Leland Stanford Junior University System for optical stimulation of target cells
US10369378B2 (en) 2007-01-10 2019-08-06 The Board Of Trustees Of The Leland Stanford Junior University System for optical stimulation of target cells
US11007374B2 (en) 2007-01-10 2021-05-18 The Board Of Trustees Of The Leland Stanford Junior University System for optical stimulation of target cells
US8864805B2 (en) 2007-01-10 2014-10-21 The Board Of Trustees Of The Leland Stanford Junior University System for optical stimulation of target cells
US10105551B2 (en) 2007-01-10 2018-10-23 The Board Of Trustees Of The Leland Stanford Junior University System for optical stimulation of target cells
US9693692B2 (en) 2007-02-14 2017-07-04 The Board Of Trustees Of The Leland Stanford Junior University System, method and applications involving identification of biological circuits such as neurological characteristics
US9757587B2 (en) 2007-03-01 2017-09-12 The Board Of Trustees Of The Leland Stanford Junior University Optogenetic method for generating an inhibitory current in a mammalian neuron
US9855442B2 (en) 2007-03-01 2018-01-02 The Board Of Trustees Of The Leland Stanford Junior University Method for optically controlling a neuron with a mammalian codon optimized nucleotide sequence that encodes a variant opsin polypeptide derived from natromonas pharaonis (NpHR)
US10589123B2 (en) 2007-03-01 2020-03-17 The Board Of Trustees Of The Leland Stanford Junior University Systems, methods and compositions for optical stimulation of target cells
US9284353B2 (en) 2007-03-01 2016-03-15 The Board Of Trustees Of The Leland Stanford Junior University Mammalian codon optimized nucleotide sequence that encodes a variant opsin polypeptide derived from Natromonas pharaonis (NpHR)
US10426970B2 (en) 2007-10-31 2019-10-01 The Board Of Trustees Of The Leland Stanford Junior University Implantable optical stimulators
US10035027B2 (en) 2007-10-31 2018-07-31 The Board Of Trustees Of The Leland Stanford Junior University Device and method for ultrasonic neuromodulation via stereotactic frame based technique
US10434327B2 (en) 2007-10-31 2019-10-08 The Board Of Trustees Of The Leland Stanford Junior University Implantable optical stimulators
US9249200B2 (en) 2008-04-23 2016-02-02 The Board Of Trustees Of The Leland Stanford Junior University Expression vector comprising a nucleotide sequence encoding a Volvox carteri light-activated ion channel protein (VChR1) and implantable device thereof
US8815582B2 (en) 2008-04-23 2014-08-26 The Board Of Trustees Of The Leland Stanford Junior University Mammalian cell expressing Volvox carteri light-activated ion channel protein (VChR1)
US9878176B2 (en) 2008-04-23 2018-01-30 The Board Of Trustees Of The Leland Stanford Junior University System utilizing Volvox carteri light-activated ion channel protein (VChR1) for optical stimulation of target cells
US8603790B2 (en) 2008-04-23 2013-12-10 The Board Of Trustees Of The Leland Stanford Junior University Systems, methods and compositions for optical stimulation of target cells
US9394347B2 (en) 2008-04-23 2016-07-19 The Board Of Trustees Of The Leland Stanford Junior University Methods for treating parkinson's disease by optically stimulating target cells
US10350430B2 (en) 2008-04-23 2019-07-16 The Board Of Trustees Of The Leland Stanford Junior University System comprising a nucleotide sequence encoding a volvox carteri light-activated ion channel protein (VCHR1)
US8729040B2 (en) 2008-05-29 2014-05-20 The Board Of Trustees Of The Leland Stanford Junior University Cell line, system and method for optical control of secondary messengers
US9453215B2 (en) 2008-05-29 2016-09-27 The Board Of Trustees Of The Leland Stanford Junior University Cell line, system and method for optical control of secondary messengers
US8962589B2 (en) 2008-05-29 2015-02-24 The Board Of Trustees Of The Leland Stanford Junior University Cell line, system and method for optical control of secondary messengers
US8956363B2 (en) 2008-06-17 2015-02-17 The Board Of Trustees Of The Leland Stanford Junior University Methods, systems and devices for optical stimulation of target cells using an optical transmission element
US10711242B2 (en) 2008-06-17 2020-07-14 The Board Of Trustees Of The Leland Stanford Junior University Apparatus and methods for controlling cellular development
US9084885B2 (en) 2008-06-17 2015-07-21 The Board Of Trustees Of The Leland Stanford Junior University Methods, systems and devices for optical stimulation of target cells using an optical transmission element
US9101759B2 (en) 2008-07-08 2015-08-11 The Board Of Trustees Of The Leland Stanford Junior University Materials and approaches for optical stimulation of the peripheral nervous system
US9308392B2 (en) 2008-07-08 2016-04-12 The Board Of Trustees Of The Leland Stanford Junior University Materials and approaches for optical stimulation of the peripheral nervous system
US10583309B2 (en) 2008-07-08 2020-03-10 The Board Of Trustees Of The Leland Stanford Junior University Materials and approaches for optical stimulation of the peripheral nervous system
US8716447B2 (en) 2008-11-14 2014-05-06 The Board Of Trustees Of The Leland Stanford Junior University Optically-based stimulation of target cells and modifications thereto
US10071132B2 (en) 2008-11-14 2018-09-11 The Board Of Trustees Of The Leland Stanford Junior University Optically-based stimulation of target cells and modifications thereto
US10064912B2 (en) 2008-11-14 2018-09-04 The Board Of Trustees Of The Leland Stanford Junior University Optically-based stimulation of target cells and modifications thereto
US9309296B2 (en) 2008-11-14 2016-04-12 The Board Of Trustees Of The Leland Stanford Junior University Optically-based stimulation of target cells and modifications thereto
US9458208B2 (en) 2008-11-14 2016-10-04 The Board Of Trustees Of The Leland Stanford Junior University Optically-based stimulation of target cells and modifications thereto
US9249234B2 (en) 2010-03-17 2016-02-02 The Board Of Trustees Of The Leland Stanford Junior University Light-sensitive ion-passing molecules
US9604073B2 (en) 2010-03-17 2017-03-28 The Board Of Trustees Of The Leland Stanford Junior University Light-sensitive ion-passing molecules
US9079940B2 (en) 2010-03-17 2015-07-14 The Board Of Trustees Of The Leland Stanford Junior University Light-sensitive ion-passing molecules
US9359449B2 (en) 2010-03-17 2016-06-07 The Board Of Trustees Of The Leland Stanford Junior University Light-sensitive ion-passing molecules
EP2547762A4 (en) * 2010-03-17 2013-09-04 Univ Leland Stanford Junior LIGHT-SENSITIVE ION-TURNING MOLECULES
EP3399024A1 (en) * 2010-03-17 2018-11-07 The Board of Trustees of The Leland Stanford Junior University Light-sensitive ion-passing molecules
US9850290B2 (en) 2010-11-05 2017-12-26 The Board Of Trustees Of The Leland Stanford Junior University Light-activated chimeric opsins and methods of using the same
US9340589B2 (en) 2010-11-05 2016-05-17 The Board Of Trustees Of The Leland Stanford Junior University Light-activated chimeric opsins and methods of using the same
US8932562B2 (en) 2010-11-05 2015-01-13 The Board Of Trustees Of The Leland Stanford Junior University Optically controlled CNS dysfunction
US9968652B2 (en) 2010-11-05 2018-05-15 The Board Of Trustees Of The Leland Stanford Junior University Optically-controlled CNS dysfunction
US9992981B2 (en) 2010-11-05 2018-06-12 The Board Of Trustees Of The Leland Stanford Junior University Optogenetic control of reward-related behaviors
US9175095B2 (en) 2010-11-05 2015-11-03 The Board Of Trustees Of The Leland Stanford Junior University Light-activated chimeric opsins and methods of using the same
US10568307B2 (en) 2010-11-05 2020-02-25 The Board Of Trustees Of The Leland Stanford Junior University Stabilized step function opsin proteins and methods of using the same
US9421258B2 (en) 2010-11-05 2016-08-23 The Board Of Trustees Of The Leland Stanford Junior University Optically controlled CNS dysfunction
EP3486253A1 (en) * 2010-11-05 2019-05-22 The Board of Trustees of The Leland Stanford Junior University Light-activated chimeric opsins and methods of using the same
US10252076B2 (en) 2010-11-05 2019-04-09 The Board Of Trustees Of The Leland Stanford Junior University Upconversion of light for use in optogenetic methods
EP2635108A4 (en) * 2010-11-05 2014-02-26 Univ Leland Stanford Junior LIGHT-ACTIVATED CHIMERIC OPSINES AND METHOD OF USE THEREOF
US10196431B2 (en) 2010-11-05 2019-02-05 The Board Of Trustees Of The Leland Stanford Junior University Light-activated chimeric opsins and methods of using the same
US9522288B2 (en) 2010-11-05 2016-12-20 The Board Of Trustees Of The Leland Stanford Junior University Upconversion of light for use in optogenetic methods
US10086012B2 (en) 2010-11-05 2018-10-02 The Board Of Trustees Of The Leland Stanford Junior University Control and characterization of memory function
US8696722B2 (en) 2010-11-22 2014-04-15 The Board Of Trustees Of The Leland Stanford Junior University Optogenetic magnetic resonance imaging
US10371776B2 (en) 2010-11-22 2019-08-06 The Board Of Trustees Of The Leland Stanford Junior University Optogenetic magnetic resonance imaging
US9615789B2 (en) 2010-11-22 2017-04-11 The Board Of Trustees Of The Leland Stanford Junior University Optogenetic magnetic resonance imaging
US8834546B2 (en) 2010-11-22 2014-09-16 The Board Of Trustees Of The Leland Stanford Junior University Optogenetic magnetic resonance imaging
US10018695B2 (en) 2010-11-22 2018-07-10 The Board Of Trustees Of The Leland Stanford Junior University Optogenetic magnetic resonance imaging
US10914803B2 (en) 2010-11-22 2021-02-09 The Board Of Trustees Of The Leland Stanford Junior University Optogenetic magnetic resonance imaging
US9271674B2 (en) 2010-11-22 2016-03-01 The Board Of Trustees Of The Leland Stanford Junior University Optogenetic magnetic resonance imaging
US10538560B2 (en) 2011-12-16 2020-01-21 The Board Of Trustees Of The Leland Stanford Junior University Opsin polypeptides and methods of use thereof
US9365628B2 (en) 2011-12-16 2016-06-14 The Board Of Trustees Of The Leland Stanford Junior University Opsin polypeptides and methods of use thereof
US9840541B2 (en) 2011-12-16 2017-12-12 The Board Of Trustees Of The Leland Stanford Junior University Opsin polypeptides and methods of use thereof
US9505817B2 (en) 2011-12-16 2016-11-29 The Board Of Trustees Of The Leland Stanford Junior University Opsin polypeptides and methods of use thereof
US9969783B2 (en) 2011-12-16 2018-05-15 The Board Of Trustees Of The Leland Stanford Junior University Opsin polypeptides and methods of use thereof
US10087223B2 (en) 2011-12-16 2018-10-02 The Board Of Trustees Of The Leland Stanford Junior University Opsin polypeptides and methods of use thereof
US11103723B2 (en) 2012-02-21 2021-08-31 The Board Of Trustees Of The Leland Stanford Junior University Methods for treating neurogenic disorders of the pelvic floor
EP2866892A4 (en) * 2012-06-29 2016-03-23 Gen Hospital Corp EMBEDDED PHOTONIC SYSTEMS AND METHOD FOR IRRADIATING A MEDIUM THEREFOR
US10188870B2 (en) 2012-11-21 2019-01-29 Circuit Therapeutics, Inc. System and method for optogenetic therapy
EP2922476A4 (en) * 2012-11-21 2016-07-13 Circuit Therapeutics Inc SYSTEM AND METHOD FOR OPTOGENETIC THERAPY
US10022553B2 (en) 2012-11-21 2018-07-17 Circuit Therapeutics, Inc. System and method for optogenetic therapy
JP2016509487A (ja) * 2012-11-21 2016-03-31 サーキット セラピューティクス， インコーポレイテッド 光遺伝学的治療のためのシステムおよび方法
US9821170B2 (en) 2012-11-21 2017-11-21 Circuit Therapeutics, Inc. System and method for optogenetic therapy
US10512787B2 (en) 2012-11-21 2019-12-24 Circuit Therapeutics, Inc. System and method for optogenetic therapy
US9814900B2 (en) 2012-11-21 2017-11-14 Circuit Therapeutics, Inc. System and method for optogenetic therapy
US10213617B2 (en) 2012-11-21 2019-02-26 Circuit Therapeutics, Inc. System and method for optogenetic therapy
US9662508B2 (en) 2012-11-21 2017-05-30 Circuit Therapeutics, Inc. System and method for optogenetic therapy
US10022552B2 (en) 2012-11-21 2018-07-17 Circuit Therapeutics, Inc. System and method for optogenetic therapy
US10105550B2 (en) 2012-11-21 2018-10-23 Circuit Therapeutics, Inc. System and method for optogenetic therapy
US9649503B2 (en) 2012-11-21 2017-05-16 Circuit Therapeutic, Inc. System and method for optogenetic therapy
US9636380B2 (en) 2013-03-15 2017-05-02 The Board Of Trustees Of The Leland Stanford Junior University Optogenetic control of inputs to the ventral tegmental area
US10974064B2 (en) 2013-03-15 2021-04-13 The Board Of Trustees Of The Leland Stanford Junior University Optogenetic control of behavioral state
US10220092B2 (en) 2013-04-29 2019-03-05 The Board Of Trustees Of The Leland Stanford Junior University Devices, systems and methods for optogenetic modulation of action potentials in target cells
US10307609B2 (en) 2013-08-14 2019-06-04 The Board Of Trustees Of The Leland Stanford Junior University Compositions and methods for controlling pain
US10568516B2 (en) 2015-06-22 2020-02-25 The Board Of Trustees Of The Leland Stanford Junior University Methods and devices for imaging and/or optogenetic control of light-responsive neurons
WO2018085253A1 (en) * 2016-11-01 2018-05-11 Massachusetts Institute Of Technology Transdermal optogenetic peripheral nerve stimulation
US11504530B2 (en) 2016-11-01 2022-11-22 Massachusetts Institute Of Technology Transdermal optogenetic peripheral nerve stimulation
US11294165B2 (en) 2017-03-30 2022-04-05 The Board Of Trustees Of The Leland Stanford Junior University Modular, electro-optical device for increasing the imaging field of view using time-sequential capture

Also Published As

Publication number Publication date
JP2017170163A (ja) 2017-09-28
CN106422081A (zh) 2017-02-22
EP2635341B1 (en) 2018-08-08
CA2817175A1 (en) 2012-05-10
AU2016202003B2 (en) 2018-06-14
JP2014502177A (ja) 2014-01-30
US20160317658A1 (en) 2016-11-03
US20190217118A1 (en) 2019-07-18
US10252076B2 (en) 2019-04-09
CN103313752A (zh) 2013-09-18
JP6505158B2 (ja) 2019-04-24
JP6145043B2 (ja) 2017-06-07
AU2011323231A1 (en) 2013-05-09
US20140148880A1 (en) 2014-05-29
EP2635341A1 (en) 2013-09-11
CN110215614A (zh) 2019-09-10
AU2011323231B2 (en) 2016-01-07
CN103313752B (zh) 2016-10-19
AU2016202003A1 (en) 2016-04-21
ES2690172T3 (es) 2018-11-19
CA2817175C (en) 2019-09-24
CN106422081B (zh) 2019-06-21
US9522288B2 (en) 2016-12-20
EP2635341A4 (en) 2016-05-25

Similar Documents

Publication Publication Date Title
US10252076B2 (en) Upconversion of light for use in optogenetic methods
JP2014502177A5 (cg-RX-API-DMAC7.html)
Bansal et al. Towards translational optogenetics
ES2725951T3 (es) Proteínas de canales aniónicos activadas por la luz modificadas por ingeniería genética y métodos de uso de las mismas
US10307609B2 (en) Compositions and methods for controlling pain
JP6549559B2 (ja) 標的細胞における活動電位の光遺伝学的調節のための装置、システム及び方法
CN103339505B (zh) 精神病状态的控制和表征
EP2968997B1 (en) Optogenetic control of behavioral state
CN109069852A (zh) 通过皮肤转移遗传信息调节疼痛和搔痒的系统和方法

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 11838859

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2013537855

Country of ref document: JP

Kind code of ref document: A

ENP Entry into the national phase

Ref document number: 2817175

Country of ref document: CA

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 2011323231

Country of ref document: AU

Date of ref document: 20111104

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 2011838859

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 13882703

Country of ref document: US