WO2015148974A2 - Engineered light-activated anion channel proteins and methods of use thereof - Google Patents

Engineered light-activated anion channel proteins and methods of use thereof Download PDF

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Publication number
WO2015148974A2
WO2015148974A2 PCT/US2015/023087 US2015023087W WO2015148974A2 WO 2015148974 A2 WO2015148974 A2 WO 2015148974A2 US 2015023087 W US2015023087 W US 2015023087W WO 2015148974 A2 WO2015148974 A2 WO 2015148974A2
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Prior art keywords
amino acid
seq
acid sequence
residue
polypeptide
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PCT/US2015/023087
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English (en)
French (fr)
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WO2015148974A3 (en
Inventor
Karl A. DEISSEROTH
Soo Yeun Lee
Charu RAMAKRISHNAN
Andre Berndt
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Leland Stanford Junior University
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Leland Stanford Junior University
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Priority to US15/126,859 priority Critical patent/US10052383B2/en
Priority to ES15770114T priority patent/ES2725951T3/es
Priority to AU2015237265A priority patent/AU2015237265A1/en
Priority to CN201580028022.1A priority patent/CN106459138A/zh
Priority to EP19156461.6A priority patent/EP3581580A1/en
Priority to JP2016559160A priority patent/JP2017511129A/ja
Priority to EP15770114.5A priority patent/EP3122761B1/en
Priority to CA2943367A priority patent/CA2943367A1/en
Application filed by Leland Stanford Junior University filed Critical Leland Stanford Junior University
Publication of WO2015148974A2 publication Critical patent/WO2015148974A2/en
Publication of WO2015148974A3 publication Critical patent/WO2015148974A3/en
Anticipated expiration legal-status Critical
Priority to US16/057,639 priority patent/US10478499B2/en
Priority to US16/600,076 priority patent/US20200030446A1/en
Ceased legal-status Critical Current

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    • 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
    • A61K41/0042—Photocleavage of drugs in vivo, e.g. cleavage of photolabile linkers in vivo by UV radiation for releasing the pharmacologically-active agent from the administered agent; photothrombosis or photoocclusion
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/405—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from algae
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif

Definitions

  • the polypeptide comprises an amino acid sequence that is at least 75%, at least 80%>, at least 85%, at least 90%, at least 95%, at least 98%), or at least 99% identical, or is 100% identical, identical to the amino acid sequence provided in SEQ ID NO:56 and comprises 1, 2, 3, 4, 5, 6, 7, 8, or 9 amino acid substitutions selected from T99S, E130S, E141S, E163S, V157K, H174R, A286N, P282K and/or N298Q, relative to the amino acid sequence of ReaChR (SEQ ID NO:81).
  • the first 51 N-terminal amino acid residues are replaced by the following amino acids residues:
  • light-activated protein means a protein that undergoes a
  • an effective dosage of a drug, compound, or pharmaceutical composition is an amount sufficient to accomplish prophylactic or therapeutic treatment either directly or indirectly.
  • an effective dosage of a drag, compound, or pharmaceutical composition may or may not be achieved in conjunction with another drug, compound, or pharmaceutical composition.
  • an "effective dosage" may be considered in the context of administering one or more therapeutic agents, and a single agent may be considered to be given in an effective amount if, in conjunction with one or more other agents, a desirable result may be or is achieved.
  • a subject light-activated anion channel polypeptide comprises an amino acid sequence having at least 58%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100%, amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: l ; and comprises V156K, H173R, V281K, and N297Q substitutions relative to the amino acid sequence of C1C2 (SEQ ID NO: 78).
  • This polypeptide is referred to herein as ClC2_4x.
  • KSRITSEGEYIPLDQIDINV (SEQ ID NO:83)
  • FCYENEV (SEQ ID NO: 84)
  • a subject light-activated anion channel polypeptide comprises an amino acid sequence having at least 60%>, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%o, at least 99%, or 100%, amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO:95; and comprises 98S, 122N, 129Q, 140S, 156R, 162S, 281R, 285N, 297Q and 312S, and comprises 195N, where the amino acid numbering is as set forth in SEQ ID NO: 95.
  • a subject engineered light-activated anion channel polypeptide comprises an amino acid sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100% amino acid sequence identity to the amino acid sequence set forth SEQ ID NO: 100; and comprises 98S, 122N, 129Q, 140S, 156R, 162S, 281R, 285N, 297Q and 312S; and comprises 167S, where the amino acid numbering is as set forth in SEQ ID NO: 100.
  • a subject engineered light- activated anion channel polypeptide comprises the amino acid sequence provided in SEQ ID NO: 100.
  • a subject engineered light-activated anion channel polypeptide comprises an amino acid sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100%, amino acid sequence identity to the amino acid sequence set forth SEQ ID NO:105; and comprises 98S, 122N, 129Q, 140S, 156R, 162S, 281R, 285N, 297Q and 312S; comprises 167S; and comprises 195C, where the amino acid numbering is as set forth in SEQ ID NO: 105.
  • a subject engineered light-activated anion channel polypeptide comprises an amino acid sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100%, amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 109; and comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 of: 59S, 83N, 90Q, 101 S, 117R, 123S, 242R, 246N, 258Q and 273S; and comprises 128S, where the amino acid numbering is as set forth in SEQ ID NO: 109.
  • a subject anion channel polypeptide comprises a membrane trafficking signal (e.g., KSRITSEGEYIPLDQIDINV (SEQ ID NO:83)).
  • a subject anion channel polypeptide comprises an ER export signal (e.g., FCYENEV (SEQ ID NO:84)).
  • a subject anion channel polypeptide comprises both a membrane trafficking signal (e.g., KSRITSEGEYIPLDQIDINV (SEQ ID NO:83)) and an ER export signal (e.g., FCYENEV (SEQ ID NO:84)).
  • amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: l 15; and comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 of: 59S, 83N, 90Q, 101 S, 117R, 123S, 242R, 246N, 258Q and 273S; and comprises 128S and 156N, where the amino acid numbering is as set forth in SEQ ID NO: l 15.
  • amino acid sequence identity to the amino acid sequence set forth SEQ ID NO:41; and comprises 1, 2, 3, 4, 5, 6, 7, 8, or 9 of: S98, S129, S140, S162, K156, R173, N285, K281, and Q297; comprises A195; and comprises T167, where the amino acid numbering is as set forth in SEQ ID NO:41.
  • a subject engineered light-activated anion channel polypeptide [00135] In some embodiments, a subject engineered light-activated anion channel polypeptide
  • a subject anion channel polypeptide comprises a membrane trafficking signal (e.g., KSRITSEGEYIPLDQIDINV (SEQ ID NO:83)).
  • a subject anion channel polypeptide comprises an ER export signal (e.g., FCYENEV (SEQ ID NO:84)).
  • a subject anion channel polypeptide comprises both a membrane trafficking signal (e.g., KSRITSEGEYIPLDQIDINV (SEQ ID NO:83)) and an ER export signal (e.g., FCYENEV (SEQ ID NO:84)).
  • amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO:49; and comprises 1, 2, 3, 4, 5, 6, 7, 8, or 9 of: S59, S90, SlOl, S123, K117, R134, N246, K242, and Q258; and comprises S128, where the amino acid numbering is as set forth in SEQ ID NO:49.
  • KSRITSEGEYIPLDQIDINV (SEQ ID NO:83)
  • FCYENEV (SEQ ID NO: 84)
  • amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO:51; and comprises 1, 2, 3, 4, 5, 6, 7, 8, or 9 of: S59, S90, SlOl, S123, K117, R134, N246, K242, and Q258; and comprises T128 and N156, where the amino acid numbering is as set forth in SEQ ID NO:51.
  • KSRITSEGEYIPLDQIDINV (SEQ ID NO:83)
  • FCYENEV (SEQ ID NO: 84)
  • a subject engineered light-activated anion channel polypeptide comprises an amino acid sequence having at least 58%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100%, amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO:52; and comprises S59, S90, SlOl, S123, Kl 17, R134, N246, K242, and Q258; and comprises A128 and A156, where the amino acid numbering is as set forth in SEQ ID NO:52.
  • KSRITSEGEYIPLDQIDINV (SEQ ID NO:83)
  • FCYENEV (SEQ ID NO: 84)
  • a subject anion channel polypeptide comprises a membrane trafficking signal (e.g., KSRITSEGEYIPLDQIDINV (SEQ ID NO:83)). In any one of these embodiments, a subject anion channel polypeptide comprises an ER export signal (e.g., FCYENEV (SEQ ID NO:84)). In any one of these embodiments, a subject anion channel polypeptide comprises both a membrane trafficking signal (e.g., KSRITSEGEYIPLDQIDINV (SEQ ID NO:83)). In any one of these embodiments, a subject anion channel polypeptide comprises an ER export signal (e.g., FCYENEV (SEQ ID NO:84)). In any one of these embodiments, a subject anion channel polypeptide comprises both a membrane trafficking signal (e.g.,
  • a subject engineered light-activated anion channel polypeptide is based on the amino acid sequence of the protein C1V1 (SEQ ID NO:80), wherein the amino acid sequence has been modified by replacing the first 50 N-terminal amino acids of C1V1 with amino acids 1-11 from the protein ChR2 (MDYGGALSAVG) (SEQ ID NO:82).
  • a subject engineered light-activated anion channel polypeptide is based on the amino acid sequence of the protein C1V1, wherein the cysteine amino acid residue at position 167 has been replaced by a serine residue.
  • a subject engineered light- activated anion channel polypeptide comprises an amino acid sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100%, amino acid sequence identity to the amino acid sequence set forth SEQ ID NO:133; and comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 of: 98S, 122N, 129Q, 140S, 156R, 162S, 281R, 285N, 297Q, and 312S; and comprises 167S, where the amino acid numbering is as set forth in SEQ ID NO: 133.
  • a subject engineered light-activated anion channel polypeptide comprises an amino acid sequence having at least 60%>, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100%, amino acid sequence identity to the amino acid sequence set forth SEQ ID NO:136; and comprises 98S, 122N, 129Q, 140S, 156R, 162S, 281R, 285N, 297Q, and 312S; comprises 167A; and comprises 195C, where the amino acid numbering is as set forth in SEQ ID NO: 136.
  • amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO:144; and comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 of: 59S, 83N, 90Q, 101S, 117R, 123S, 242R, 246N, 258Q and 273S; and comprises 128T and 156N, where the amino acid numbering is as set forth in SEQ ID NO:144.
  • a subject engineered light-activated anion channel polypeptide comprises an amino acid sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100%, amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 146; and comprises 59S, 83N, 90Q, 101 S, 117R, 123S, 242R, 246N, 258Q and 273S; and comprises 128A and 156N, where the amino acid numbering is as set forth in SEQ ID NO: 146.
  • a subject anion channel polypeptide comprises a membrane trafficking signal (e.g., KSRITSEGEYIPLDQIDINV (SEQ ID NO:83)).
  • a subject anion channel polypeptide comprises an ER export signal (e.g., FCYENEV (SEQ ID NO:84)).
  • a subject engineered light-activated anion channel polypeptide comprises an amino acid sequence having at least 58%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100%, amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO:73; and comprises S59, S90, SlOl, S123, Kl 17, R134, N246, K242, and Q258; and comprises T128 and N156, where the amino acid numbering is as set forth in SEQ ID NO: 73.
  • the amino acid sequence of the ReaChR protein has been modified by introducing one or more of the following mutations into the amino acid sequence: T99S, E123N, E130Q, E141 S, V157R, E163S, P282R, A286N, N298Q and/or E313S.
  • a subject engineered light-activated anion channel polypeptide comprises the amino acid sequence of the protein ReaChR with all 10 of the above-listed amino acid substitutions, such that the amino acid sequence of the polypeptide is provided in SEQ ID NO: 149.
  • a subject engineered light-activated anion channel polypeptide comprises an amino acid sequence having at least 60%>, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100%, amino acid sequence identity to the amino acid sequence set forth SEQ ID NO: 155; and comprises 99S, 123N, 130Q, 141 S, 157R, 163S, 282R, 286N, 298Q and 313S; and comprises 168S, where the amino acid numbering is as set forth in SEQ ID NO: 155.
  • a subject engineered light-activated anion channel polypeptide comprises an amino acid sequence having at least 60%>, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99%, or 100%, amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 168; and comprises 59S, 83N, 90Q, 101 S, 117R, 123S, 242R, 246N, 258Q and 273S; and comprises 128A and 156N, where the amino acid numbering is as set forth in SEQ ID NO: 168.
  • a subject engineered light-activated anion channel polypeptide is based on the amino acid sequence of the protein ChR2, wherein the cysteine amino acid residue at position 128 has been replaced by an alanine residue.
  • a subject engineered light-activated anion channel polypeptide comprises an amino acid sequence having at least 58%), at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%), at least 98%), at least 99%, or 100%), amino acid sequence identity to the amino acid sequence set forth SEQ ID NO:26; and comprises 1, 2, 3, 4, 5, 6, 7, 8, or 9 of: S59, S90, S101, S123, Kl 17, R134, K242, N246 and Q258; and comprises A128, where the amino acid numbering is as set forth in SEQ ID NO:26.
  • a subject anion channel polypeptide comprises both a membrane trafficking signal (e.g., KSRITSEGEYIPLDQIDINV (SEQ ID NO:83)) and an ER export signal (e.g., FCYENEV (SEQ ID NO:84)).
  • a membrane trafficking signal e.g., KSRITSEGEYIPLDQIDINV (SEQ ID NO:83)
  • an ER export signal e.g., FCYENEV (SEQ ID NO:84)
  • amino acid sequence identity to the amino acid sequence set forth SEQ ID NO:33; and comprises 1, 2, 3, 4, 5, 6, 7, 8, or 9 of: S59, S90, S101, S123, K117, R134, K242, N246 and Q258; comprises Nl 56; and comprises S128, where the amino acid numbering is as set forth in SEQ ID NO:33.
  • a subject anion channel polypeptide comprises both a membrane trafficking signal (e.g., KSRITSEGEYIPLDQIDINV (SEQ ID NO:83)) and an ER export signal (e.g., FCYENEV (SEQ ID NO:84)).
  • a membrane trafficking signal e.g., KSRITSEGEYIPLDQIDINV (SEQ ID NO:83)
  • an ER export signal e.g., FCYENEV (SEQ ID NO:84)
  • a portion of a polynucleotide encoding a subject protein is operably linked to a promoter sequence.
  • Any suitable promoter that functions in a target cell can be used for expression of the subject polynucleotides.
  • a promoter sequence can be a promoter that is specific to a particular target cell type or to a particular tissue type, such as a particular neuron or a pan-neuronal promoter.
  • Initiation control regions of promoters which are useful to drive expression of polynucleotides in a specific animal cell, are numerous and familiar to those skilled in the art. Virtually any promoter capable of driving expression of the subject polynucleotides can be used.
  • the replication-defective recombinant AAVs according to the present disclosure can be prepared by co-transfecting a plasmid containing the nucleic acid sequence of interest flanked by two AAV inverted terminal repeat (ITR) regions, and a plasmid carrying the AAV encapsidation genes (rep and cap genes), into a cell line that is infected with a human helper virus (for example an adenovirus).
  • ITR inverted terminal repeat
  • rep and cap genes AAV encapsidation genes
  • Another major viral transduction system utilizes lentivirus including the following potential expression vectors: pLenti-CamKII-iChR-XFP, pLenti-Efl a-iChR-XFP, pLenti-mThyl -iChR-XFP, pLenti-hThyl-iChR-XFP, pLenti-hSyn-iChR-XFP, pLenti-VGAT-iChR-XFP, pLenti-Hcrt-iChRXFP.
  • Herpes simplex virus HSV
  • HSV Herpes simplex virus
  • Suitable Shigella strains include, but are not limited to, Shigella flexneri, Shigella sonnei, and Shigella disenteriae.
  • the laboratory strain is one that is non-pathogenic.
  • suitable bacteria include, but are not limited to, Bacillus subtilis, Pseudomonas pudita, Pseudomonas aeruginosa, Pseudomonas mevalonii, Rhodobacter sphaeroides, Rhodobacter capsulatus, Rhodospirillum rubrum, Rhodococcus sp., and the like.
  • the host cell is Escherichia coli.
  • the light-generating device may comprise a light emitting diode
  • a light generating device may generate blue light having a wavelength ranging from about 475 nm to about 500 nm.
  • a light generating device may generate green light having a wavelength ranging from about 500 nm to about 560 nm.
  • a light generating device may generate yellow light having a wavelength ranging from about 560 nm to about 590 nm.
  • a light generating device may generate orange light having a wavelength ranging from about 590 nm to about 620 nm.
  • a light generating device may generate red light having a wavelength ranging from about 620 nm to about 650 nm.

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PCT/US2015/023087 2014-03-28 2015-03-27 Engineered light-activated anion channel proteins and methods of use thereof Ceased WO2015148974A2 (en)

Priority Applications (10)

Application Number Priority Date Filing Date Title
EP15770114.5A EP3122761B1 (en) 2014-03-28 2015-03-27 Engineered light-activated anion channel proteins and methods of use thereof
AU2015237265A AU2015237265A1 (en) 2014-03-28 2015-03-27 Engineered light-activated anion channel proteins and methods of use thereof
CN201580028022.1A CN106459138A (zh) 2014-03-28 2015-03-27 工程化的光激活阴离子通道蛋白及其使用方法
EP19156461.6A EP3581580A1 (en) 2014-03-28 2015-03-27 Engineered light-activated anion channel proteins and methods of use thereof
JP2016559160A JP2017511129A (ja) 2014-03-28 2015-03-27 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
US15/126,859 US10052383B2 (en) 2014-03-28 2015-03-27 Engineered light-activated anion channel proteins and methods of use thereof
ES15770114T ES2725951T3 (es) 2014-03-28 2015-03-27 Proteínas de canales aniónicos activadas por la luz modificadas por ingeniería genética y métodos de uso de las mismas
CA2943367A CA2943367A1 (en) 2014-03-28 2015-03-27 Engineered light-activated anion channel proteins and methods of use thereof
US16/057,639 US10478499B2 (en) 2014-03-28 2018-08-07 Engineered light-activated anion channel proteins and methods of use thereof
US16/600,076 US20200030446A1 (en) 2014-03-28 2019-10-11 Engineered light-activated anion channel proteins and methods of use thereof

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US201461972182P 2014-03-28 2014-03-28
US61/972,182 2014-03-28

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US16/057,639 Division US10478499B2 (en) 2014-03-28 2018-08-07 Engineered light-activated anion channel proteins and methods of use thereof

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CN (1) CN106459138A (enExample)
AU (1) AU2015237265A1 (enExample)
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Cited By (20)

* Cited by examiner, † Cited by third party
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WO2017048808A1 (en) * 2015-09-15 2017-03-23 The Board Of Trustees Of The Leland Stanford Junior University Light-responsive polypeptides and methods of use thereof
CN108192896A (zh) * 2018-02-10 2018-06-22 中国烟草总公司郑州烟草研究院 一个烟草慢阴离子通道蛋白NtSLAH1及其应用
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)
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
US10371776B2 (en) 2010-11-22 2019-08-06 The Board Of Trustees Of The Leland Stanford Junior University Optogenetic magnetic resonance imaging
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
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