RU2595384C2 - Мутантный канальный родопсин-2 - Google Patents
Мутантный канальный родопсин-2 Download PDFInfo
- Publication number
- RU2595384C2 RU2595384C2 RU2013115454/10A RU2013115454A RU2595384C2 RU 2595384 C2 RU2595384 C2 RU 2595384C2 RU 2013115454/10 A RU2013115454/10 A RU 2013115454/10A RU 2013115454 A RU2013115454 A RU 2013115454A RU 2595384 C2 RU2595384 C2 RU 2595384C2
- Authority
- RU
- Russia
- Prior art keywords
- cell
- light
- channel
- cys
- ion channel
- Prior art date
Links
- 239000011575 calcium Substances 0.000 claims abstract description 106
- 102000004310 Ion Channels Human genes 0.000 claims abstract description 69
- 108090000862 Ion Channels Proteins 0.000 claims abstract description 69
- 108091006146 Channels Proteins 0.000 claims abstract description 48
- 108010035848 Channelrhodopsins Proteins 0.000 claims abstract description 24
- 229910052791 calcium Inorganic materials 0.000 claims abstract description 15
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims abstract description 13
- YFHXZQPUBCBNIP-UHFFFAOYSA-N fura-2 Chemical compound CC1=CC=C(N(CC(O)=O)CC(O)=O)C(OCCOC=2C(=CC=3OC(=CC=3C=2)C=2OC(=CN=2)C(O)=O)N(CC(O)=O)CC(O)=O)=C1 YFHXZQPUBCBNIP-UHFFFAOYSA-N 0.000 claims abstract description 10
- 210000004027 cell Anatomy 0.000 claims description 170
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 91
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 75
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 48
- 230000001965 increasing effect Effects 0.000 claims description 45
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims description 38
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims description 36
- 239000012528 membrane Substances 0.000 claims description 36
- 150000001413 amino acids Chemical group 0.000 claims description 33
- 230000002207 retinal effect Effects 0.000 claims description 26
- 206010034972 Photosensitivity reaction Diseases 0.000 claims description 23
- 238000000034 method Methods 0.000 claims description 23
- 230000036211 photosensitivity Effects 0.000 claims description 23
- 230000000638 stimulation Effects 0.000 claims description 21
- 150000007523 nucleic acids Chemical class 0.000 claims description 20
- 108020004707 nucleic acids Proteins 0.000 claims description 18
- 102000039446 nucleic acids Human genes 0.000 claims description 18
- 210000004295 hippocampal neuron Anatomy 0.000 claims description 16
- 239000013604 expression vector Substances 0.000 claims description 15
- 238000006467 substitution reaction Methods 0.000 claims description 15
- 108090000623 proteins and genes Proteins 0.000 claims description 14
- 241000700605 Viruses Species 0.000 claims description 13
- 238000013537 high throughput screening Methods 0.000 claims description 13
- 230000001404 mediated effect Effects 0.000 claims description 10
- 239000013598 vector Substances 0.000 claims description 10
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 8
- 235000004279 alanine Nutrition 0.000 claims description 8
- 230000008859 change Effects 0.000 claims description 8
- 238000001415 gene therapy Methods 0.000 claims description 8
- 239000002773 nucleotide Substances 0.000 claims description 7
- 150000003726 retinal derivatives Chemical class 0.000 claims description 7
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 6
- 210000004962 mammalian cell Anatomy 0.000 claims description 6
- 125000003729 nucleotide group Chemical group 0.000 claims description 6
- 239000011591 potassium Substances 0.000 claims description 6
- 229910052700 potassium Inorganic materials 0.000 claims description 6
- NCYCYZXNIZJOKI-OVSJKPMPSA-N retinal group Chemical group C\C(=C/C=O)\C=C\C=C(\C=C\C1=C(CCCC1(C)C)C)/C NCYCYZXNIZJOKI-OVSJKPMPSA-N 0.000 claims description 6
- 208000003098 Ganglion Cysts Diseases 0.000 claims description 5
- 208000005400 Synovial Cyst Diseases 0.000 claims description 5
- 230000007423 decrease Effects 0.000 claims description 5
- 239000004475 Arginine Substances 0.000 claims description 4
- 241000238631 Hexapoda Species 0.000 claims description 4
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 4
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims description 4
- 239000004473 Threonine Substances 0.000 claims description 4
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 4
- 210000004978 chinese hamster ovary cell Anatomy 0.000 claims description 4
- 201000001441 melanoma Diseases 0.000 claims description 4
- 210000003994 retinal ganglion cell Anatomy 0.000 claims description 4
- 238000012546 transfer Methods 0.000 claims description 4
- 241000235058 Komagataella pastoris Species 0.000 claims description 3
- 239000004472 Lysine Substances 0.000 claims description 3
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims description 3
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 claims description 3
- 125000000539 amino acid group Chemical group 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 238000003384 imaging method Methods 0.000 claims description 3
- 201000000050 myeloid neoplasm Diseases 0.000 claims description 3
- 210000000608 photoreceptor cell Anatomy 0.000 claims description 3
- 238000012800 visualization Methods 0.000 claims description 3
- MIMKOTXYWWOEFT-UHFFFAOYSA-N 3,7-dimethyldeca-2,4,6,8-tetraenal Chemical compound CC=CC(C)=CC=CC(C)=CC=O MIMKOTXYWWOEFT-UHFFFAOYSA-N 0.000 claims description 2
- UDYGWSPUYSRWRN-UHFFFAOYSA-N 3,7-dimethylocta-2,4,6-trienal Chemical compound CC(C)=CC=CC(C)=CC=O UDYGWSPUYSRWRN-UHFFFAOYSA-N 0.000 claims description 2
- QPRQNCDEPWLQRO-UHFFFAOYSA-N 3R-hydroxy-all-trans-retinal Natural products O=CC=C(C)C=CC=C(C)C=CC1=C(C)CC(O)CC1(C)C QPRQNCDEPWLQRO-UHFFFAOYSA-N 0.000 claims description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims description 2
- 241000235347 Schizosaccharomyces pombe Species 0.000 claims description 2
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims description 2
- QPRQNCDEPWLQRO-DAWLFQHYSA-N all-trans-3-Hydroxyretinal Chemical compound O=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CC(O)CC1(C)C QPRQNCDEPWLQRO-DAWLFQHYSA-N 0.000 claims description 2
- CYVVUYORRQQAQE-RMWYGNQTSA-N all-trans-4-hydroxyretinal Chemical compound O=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)C(O)CCC1(C)C CYVVUYORRQQAQE-RMWYGNQTSA-N 0.000 claims description 2
- 235000003704 aspartic acid Nutrition 0.000 claims description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 2
- 210000001052 bipolar neuron Anatomy 0.000 claims description 2
- 235000013922 glutamic acid Nutrition 0.000 claims description 2
- 239000004220 glutamic acid Substances 0.000 claims description 2
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 claims description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 210000003078 multipolar neuron Anatomy 0.000 claims description 2
- 210000001176 projection neuron Anatomy 0.000 claims description 2
- 210000001510 pseudounipolar neuron Anatomy 0.000 claims description 2
- 210000000449 purkinje cell Anatomy 0.000 claims description 2
- 235000020945 retinal Nutrition 0.000 claims 8
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 claims 1
- 210000005253 yeast cell Anatomy 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 19
- 239000000126 substance Substances 0.000 abstract description 10
- 125000003275 alpha amino acid group Chemical group 0.000 abstract 2
- 238000009877 rendering Methods 0.000 abstract 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 89
- 210000002569 neuron Anatomy 0.000 description 37
- 239000000243 solution Substances 0.000 description 29
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 22
- 230000004913 activation Effects 0.000 description 21
- 210000003050 axon Anatomy 0.000 description 20
- NCYCYZXNIZJOKI-UHFFFAOYSA-N vitamin A aldehyde Natural products O=CC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C NCYCYZXNIZJOKI-UHFFFAOYSA-N 0.000 description 20
- 238000002474 experimental method Methods 0.000 description 19
- 230000035699 permeability Effects 0.000 description 19
- 230000014509 gene expression Effects 0.000 description 18
- 230000035772 mutation Effects 0.000 description 15
- 235000001014 amino acid Nutrition 0.000 description 14
- 210000000287 oocyte Anatomy 0.000 description 14
- 230000001419 dependent effect Effects 0.000 description 13
- 230000028161 membrane depolarization Effects 0.000 description 13
- 230000003834 intracellular effect Effects 0.000 description 12
- 230000004044 response Effects 0.000 description 12
- 239000011734 sodium Substances 0.000 description 12
- 210000001787 dendrite Anatomy 0.000 description 11
- 238000005259 measurement Methods 0.000 description 11
- 239000011780 sodium chloride Substances 0.000 description 11
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 10
- 230000036982 action potential Effects 0.000 description 10
- 230000004438 eyesight Effects 0.000 description 10
- 230000004941 influx Effects 0.000 description 10
- 102000004169 proteins and genes Human genes 0.000 description 10
- 108010092555 Large-Conductance Calcium-Activated Potassium Channels Proteins 0.000 description 9
- 102000016469 Large-Conductance Calcium-Activated Potassium Channels Human genes 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 9
- 239000011777 magnesium Substances 0.000 description 9
- 210000002763 pyramidal cell Anatomy 0.000 description 9
- 230000002336 repolarization Effects 0.000 description 9
- 108010062745 Chloride Channels Proteins 0.000 description 8
- 102000011045 Chloride Channels Human genes 0.000 description 8
- 108020004414 DNA Proteins 0.000 description 8
- 239000007995 HEPES buffer Substances 0.000 description 8
- 230000005284 excitation Effects 0.000 description 8
- 239000001963 growth medium Substances 0.000 description 8
- 230000008569 process Effects 0.000 description 8
- 238000001228 spectrum Methods 0.000 description 8
- 238000005286 illumination Methods 0.000 description 7
- 239000000543 intermediate Substances 0.000 description 7
- 230000003211 malignant effect Effects 0.000 description 7
- 235000018102 proteins Nutrition 0.000 description 7
- 108091005957 yellow fluorescent proteins Proteins 0.000 description 7
- 210000000170 cell membrane Anatomy 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- 230000003287 optical effect Effects 0.000 description 6
- 230000002035 prolonged effect Effects 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 238000011282 treatment Methods 0.000 description 6
- FTEDXVNDVHYDQW-UHFFFAOYSA-N BAPTA Chemical compound OC(=O)CN(CC(O)=O)C1=CC=CC=C1OCCOC1=CC=CC=C1N(CC(O)=O)CC(O)=O FTEDXVNDVHYDQW-UHFFFAOYSA-N 0.000 description 5
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 5
- 102000004257 Potassium Channel Human genes 0.000 description 5
- 239000002262 Schiff base Substances 0.000 description 5
- 150000004753 Schiff bases Chemical class 0.000 description 5
- 150000001768 cations Chemical class 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000008103 glucose Substances 0.000 description 5
- 108020001213 potassium channel Proteins 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 210000001525 retina Anatomy 0.000 description 5
- 210000000225 synapse Anatomy 0.000 description 5
- UQNAFPHGVPVTAL-UHFFFAOYSA-N 2,3-Dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline Chemical compound N1C(=O)C(=O)NC2=C1C=C([N+]([O-])=O)C1=C2C=CC=C1S(=O)(=O)N UQNAFPHGVPVTAL-UHFFFAOYSA-N 0.000 description 4
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 4
- 241000269370 Xenopus <genus> Species 0.000 description 4
- 241000269368 Xenopus laevis Species 0.000 description 4
- 229930002945 all-trans-retinaldehyde Natural products 0.000 description 4
- 210000000411 amacrine cell Anatomy 0.000 description 4
- 210000004899 c-terminal region Anatomy 0.000 description 4
- 230000010221 calcium permeability Effects 0.000 description 4
- 235000018417 cysteine Nutrition 0.000 description 4
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 4
- 230000002999 depolarising effect Effects 0.000 description 4
- 239000000975 dye Substances 0.000 description 4
- 229960004198 guanidine Drugs 0.000 description 4
- 230000000971 hippocampal effect Effects 0.000 description 4
- 210000001320 hippocampus Anatomy 0.000 description 4
- 230000001976 improved effect Effects 0.000 description 4
- 238000003780 insertion Methods 0.000 description 4
- 230000037431 insertion Effects 0.000 description 4
- 150000002500 ions Chemical class 0.000 description 4
- 239000013307 optical fiber Substances 0.000 description 4
- 108091008695 photoreceptors Proteins 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 150000003109 potassium Chemical class 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 230000000284 resting effect Effects 0.000 description 4
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
- 238000001890 transfection Methods 0.000 description 4
- 108010082845 Bacteriorhodopsins Proteins 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 238000002679 ablation Methods 0.000 description 3
- 238000001720 action spectrum Methods 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 239000002738 chelating agent Substances 0.000 description 3
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 3
- 230000004907 flux Effects 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 230000001771 impaired effect Effects 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 210000003292 kidney cell Anatomy 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 229960003975 potassium Drugs 0.000 description 3
- 210000000278 spinal cord Anatomy 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 102000035160 transmembrane proteins Human genes 0.000 description 3
- 108091005703 transmembrane proteins Proteins 0.000 description 3
- 239000013603 viral vector Substances 0.000 description 3
- 230000000007 visual effect Effects 0.000 description 3
- VOROEQBFPPIACJ-SCSAIBSYSA-N (2r)-2-amino-5-phosphonopentanoic acid Chemical compound OC(=O)[C@H](N)CCCP(O)(O)=O VOROEQBFPPIACJ-SCSAIBSYSA-N 0.000 description 2
- NCYCYZXNIZJOKI-HPNHMNAASA-N 11Z-retinal Natural products CC(=C/C=O)C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C NCYCYZXNIZJOKI-HPNHMNAASA-N 0.000 description 2
- FYIHPNCKLYPALH-UHFFFAOYSA-N 2-[2-(2-aminophenoxy)ethenoxy]aniline Chemical compound NC1=CC=CC=C1OC=COC1=CC=CC=C1N FYIHPNCKLYPALH-UHFFFAOYSA-N 0.000 description 2
- URNCTMHGJQSLOC-UHFFFAOYSA-N 4-[4-[(1z,3e)-4-[4-(dipentylamino)phenyl]buta-1,3-dienyl]pyridin-1-ium-1-yl]butane-1-sulfonate Chemical compound C1=CC(N(CCCCC)CCCCC)=CC=C1C=CC=CC1=CC=[N+](CCCCS([O-])(=O)=O)C=C1 URNCTMHGJQSLOC-UHFFFAOYSA-N 0.000 description 2
- QZXAEJGHNXJTSE-UHFFFAOYSA-N 7-(ethylamino)-4,6-dimethylchromen-2-one Chemical compound O1C(=O)C=C(C)C2=C1C=C(NCC)C(C)=C2 QZXAEJGHNXJTSE-UHFFFAOYSA-N 0.000 description 2
- 241000702423 Adeno-associated virus - 2 Species 0.000 description 2
- HJCMDXDYPOUFDY-WHFBIAKZSA-N Ala-Gln Chemical compound C[C@H](N)C(=O)N[C@H](C(O)=O)CCC(N)=O HJCMDXDYPOUFDY-WHFBIAKZSA-N 0.000 description 2
- 201000004569 Blindness Diseases 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 239000012097 Lipofectamine 2000 Substances 0.000 description 2
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 108090000526 Papain Proteins 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- HLCFGWHYROZGBI-JJKGCWMISA-M Potassium gluconate Chemical compound [K+].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O HLCFGWHYROZGBI-JJKGCWMISA-M 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 102000004330 Rhodopsin Human genes 0.000 description 2
- 108090000820 Rhodopsin Proteins 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 102000016913 Voltage-Gated Sodium Channels Human genes 0.000 description 2
- 108010053752 Voltage-Gated Sodium Channels Proteins 0.000 description 2
- 230000003376 axonal effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000002457 bidirectional effect Effects 0.000 description 2
- 238000013378 biophysical characterization Methods 0.000 description 2
- 108010006025 bovine growth hormone Proteins 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- -1 calcium-activated chlorine Chemical class 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 210000000805 cytoplasm Anatomy 0.000 description 2
- 210000000172 cytosol Anatomy 0.000 description 2
- 230000001086 cytosolic effect Effects 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000002964 excitative effect Effects 0.000 description 2
- 239000012894 fetal calf serum Substances 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- VPSRLGDRGCKUTK-UHFFFAOYSA-N fura-2-acetoxymethyl ester Chemical compound CC(=O)OCOC(=O)CN(CC(=O)OCOC(C)=O)C1=CC=C(C)C=C1OCCOC(C(=C1)N(CC(=O)OCOC(C)=O)CC(=O)OCOC(C)=O)=CC2=C1OC(C=1OC(=CN=1)C(=O)OCOC(C)=O)=C2 VPSRLGDRGCKUTK-UHFFFAOYSA-N 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 230000017813 membrane repolarization Effects 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
- 230000008587 neuronal excitability Effects 0.000 description 2
- 239000011664 nicotinic acid Substances 0.000 description 2
- 229940055729 papain Drugs 0.000 description 2
- 235000019834 papain Nutrition 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 238000006303 photolysis reaction Methods 0.000 description 2
- 230000015843 photosynthesis, light reaction Effects 0.000 description 2
- 238000007747 plating Methods 0.000 description 2
- 230000008488 polyadenylation Effects 0.000 description 2
- 229960003189 potassium gluconate Drugs 0.000 description 2
- 239000004224 potassium gluconate Substances 0.000 description 2
- 235000013926 potassium gluconate Nutrition 0.000 description 2
- 238000005086 pumping Methods 0.000 description 2
- 210000001747 pupil Anatomy 0.000 description 2
- 239000010453 quartz Substances 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 238000002741 site-directed mutagenesis Methods 0.000 description 2
- 230000003595 spectral effect Effects 0.000 description 2
- 238000004611 spectroscopical analysis Methods 0.000 description 2
- 238000012453 sprague-dawley rat model Methods 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- 230000008625 synaptic signaling Effects 0.000 description 2
- CFMYXEVWODSLAX-QOZOJKKESA-N tetrodotoxin Chemical compound O([C@@]([C@H]1O)(O)O[C@H]2[C@@]3(O)CO)[C@H]3[C@@H](O)[C@]11[C@H]2[C@@H](O)N=C(N)N1 CFMYXEVWODSLAX-QOZOJKKESA-N 0.000 description 2
- 229950010357 tetrodotoxin Drugs 0.000 description 2
- CFMYXEVWODSLAX-UHFFFAOYSA-N tetrodotoxin Natural products C12C(O)NC(=N)NC2(C2O)C(O)C3C(CO)(O)C1OC2(O)O3 CFMYXEVWODSLAX-UHFFFAOYSA-N 0.000 description 2
- 238000010361 transduction Methods 0.000 description 2
- 230000026683 transduction Effects 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 241001430294 unidentified retrovirus Species 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- NCYCYZXNIZJOKI-IOUUIBBYSA-N 11-cis-retinal Chemical compound O=C/C=C(\C)/C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C NCYCYZXNIZJOKI-IOUUIBBYSA-N 0.000 description 1
- NCYCYZXNIZJOKI-HWCYFHEPSA-N 13-cis-retinal Chemical compound O=C/C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C NCYCYZXNIZJOKI-HWCYFHEPSA-N 0.000 description 1
- WWRGFLIMFQYXRS-UHFFFAOYSA-N 3,7,11-trimethyldodeca-2,4,6,8,10-pentaenal Chemical compound CC(C)=CC=CC(C)=CC=CC(C)=CC=O WWRGFLIMFQYXRS-UHFFFAOYSA-N 0.000 description 1
- NCYCYZXNIZJOKI-MKOSUFFBSA-N 9-cis-retinal Chemical compound O=C/C=C(\C)/C=C/C=C(/C)\C=C\C1=C(C)CCCC1(C)C NCYCYZXNIZJOKI-MKOSUFFBSA-N 0.000 description 1
- 239000012103 Alexa Fluor 488 Substances 0.000 description 1
- 241000710929 Alphavirus Species 0.000 description 1
- 239000000592 Artificial Cell Substances 0.000 description 1
- 101001086405 Bos taurus Rhodopsin Proteins 0.000 description 1
- 102000005702 Calcium-Activated Potassium Channels Human genes 0.000 description 1
- 108010045489 Calcium-Activated Potassium Channels Proteins 0.000 description 1
- 102220598266 Cancer/testis antigen family 45 member A10_C36A_mutation Human genes 0.000 description 1
- 108091005462 Cation channels Proteins 0.000 description 1
- 241000195597 Chlamydomonas reinhardtii Species 0.000 description 1
- 241000282552 Chlorocebus aethiops Species 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- 206010011878 Deafness Diseases 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 241000283074 Equus asinus Species 0.000 description 1
- 101000834253 Gallus gallus Actin, cytoplasmic 1 Proteins 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101001032837 Homo sapiens Metabotropic glutamate receptor 6 Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 241000713666 Lentivirus Species 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 102100038300 Metabotropic glutamate receptor 6 Human genes 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 108091061960 Naked DNA Proteins 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 102000001675 Parvalbumin Human genes 0.000 description 1
- 108060005874 Parvalbumin Proteins 0.000 description 1
- 108700019535 Phosphoprotein Phosphatases Proteins 0.000 description 1
- 102000045595 Phosphoprotein Phosphatases Human genes 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 102220467332 Protein BEX4_L94A_mutation Human genes 0.000 description 1
- 102220465425 Protein arginine N-methyltransferase 1_L93A_mutation Human genes 0.000 description 1
- 241000711798 Rabies lyssavirus Species 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 101710150115 Sensory rhodopsin-2 Proteins 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- 241000195614 Volvox carteri Species 0.000 description 1
- 108091093126 WHP Posttrascriptional Response Element Proteins 0.000 description 1
- 241001492404 Woodchuck hepatitis virus Species 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 239000004178 amaranth Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000000823 artificial membrane Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000005441 aurora Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000005388 borosilicate glass Substances 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 230000009460 calcium influx Effects 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 230000003185 calcium uptake Effects 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 239000002458 cell surface marker Substances 0.000 description 1
- 230000010001 cellular homeostasis Effects 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 150000001804 chlorine Chemical class 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 230000027288 circadian rhythm Effects 0.000 description 1
- 238000000975 co-precipitation Methods 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 238000000942 confocal micrograph Methods 0.000 description 1
- 238000004624 confocal microscopy Methods 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
- 238000013480 data collection Methods 0.000 description 1
- 230000009849 deactivation Effects 0.000 description 1
- 231100000895 deafness Toxicity 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 239000000412 dendrimer Substances 0.000 description 1
- 229920000736 dendritic polymer Polymers 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000003372 electrophysiological method Methods 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 210000002308 embryonic cell Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 108010048367 enhanced green fluorescent protein Proteins 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000028023 exocytosis Effects 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 210000000609 ganglia Anatomy 0.000 description 1
- 238000012637 gene transfection Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 229960002518 gentamicin Drugs 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 150000002333 glycines Chemical class 0.000 description 1
- 210000002288 golgi apparatus Anatomy 0.000 description 1
- 210000004565 granule cell Anatomy 0.000 description 1
- 208000016354 hearing loss disease Diseases 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 230000006882 induction of apoptosis Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000006525 intracellular process Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000004446 light reflex Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 210000001259 mesencephalon Anatomy 0.000 description 1
- 210000002161 motor neuron Anatomy 0.000 description 1
- 230000004118 muscle contraction Effects 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 238000001208 nuclear magnetic resonance pulse sequence Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 238000009806 oophorectomy Methods 0.000 description 1
- 210000003463 organelle Anatomy 0.000 description 1
- 230000010355 oscillation Effects 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 150000004291 polyenes Chemical class 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000001242 postsynaptic effect Effects 0.000 description 1
- 230000001124 posttranscriptional effect Effects 0.000 description 1
- 229940125422 potassium channel blocker Drugs 0.000 description 1
- 239000003450 potassium channel blocker Substances 0.000 description 1
- USIVOYQBKKKGKK-UHFFFAOYSA-N potassium tetraethylazanium Chemical compound [K+].CC[N+](CC)(CC)CC USIVOYQBKKKGKK-UHFFFAOYSA-N 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 230000032554 response to blue light Effects 0.000 description 1
- 210000000964 retinal cone photoreceptor cell Anatomy 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 102220029346 rs34541442 Human genes 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000009291 secondary effect Effects 0.000 description 1
- 210000001044 sensory neuron Anatomy 0.000 description 1
- 210000000697 sensory organ Anatomy 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 231100000873 signs of neurotoxicity Toxicity 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 238000005476 soldering Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 210000001103 thalamus Anatomy 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000003151 transfection method Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000010474 transient expression Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 238000002834 transmittance Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 125000000430 tryptophan group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 229910052724 xenon Inorganic materials 0.000 description 1
- FHNFHKCVQCLJFQ-UHFFFAOYSA-N xenon atom Chemical compound [Xe] FHNFHKCVQCLJFQ-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- 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
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
-
- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
-
- 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
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/10—Cells modified by introduction of foreign genetic material
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6872—Intracellular protein regulatory factors and their receptors, e.g. including ion channels
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Medicinal Chemistry (AREA)
- Biotechnology (AREA)
- Zoology (AREA)
- Cell Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biomedical Technology (AREA)
- Biophysics (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Microbiology (AREA)
- Toxicology (AREA)
- General Engineering & Computer Science (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Food Science & Technology (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Plant Pathology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Ophthalmology & Optometry (AREA)
- Public Health (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US38079310P | 2010-09-08 | 2010-09-08 | |
| US61/380,793 | 2010-09-08 | ||
| EP10175832 | 2010-09-08 | ||
| EP10175832.4 | 2010-09-08 | ||
| PCT/EP2011/065510 WO2012032103A1 (en) | 2010-09-08 | 2011-09-08 | Mutant channelrhodopsin 2 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2013115454A RU2013115454A (ru) | 2014-10-20 |
| RU2595384C2 true RU2595384C2 (ru) | 2016-08-27 |
Family
ID=42979822
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2013115454/10A RU2595384C2 (ru) | 2010-09-08 | 2011-09-08 | Мутантный канальный родопсин-2 |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US8748578B2 (enExample) |
| EP (1) | EP2614079B1 (enExample) |
| JP (1) | JP5933556B2 (enExample) |
| KR (1) | KR101945962B1 (enExample) |
| CN (1) | CN103261219B (enExample) |
| AU (1) | AU2011298745B2 (enExample) |
| BR (1) | BR112013005634A2 (enExample) |
| CA (1) | CA2810757C (enExample) |
| DK (1) | DK2614079T3 (enExample) |
| ES (1) | ES2545992T3 (enExample) |
| HR (1) | HRP20150846T1 (enExample) |
| HU (1) | HUE025952T2 (enExample) |
| IL (1) | IL225060A (enExample) |
| MX (1) | MX347453B (enExample) |
| PL (1) | PL2614079T3 (enExample) |
| PT (1) | PT2614079E (enExample) |
| RU (1) | RU2595384C2 (enExample) |
| SG (1) | SG188409A1 (enExample) |
| SI (1) | SI2614079T1 (enExample) |
| WO (1) | WO2012032103A1 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US12234267B2 (en) | 2016-08-29 | 2025-02-25 | Wayne State University | Identification of mutations in channelopsin variants having improved light sensitivity and methods of use thereof |
Families Citing this family (50)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| US20070053996A1 (en) | 2005-07-22 | 2007-03-08 | Boyden Edward S | 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 |
| 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 |
| 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 |
| US8470790B2 (en) | 2006-05-04 | 2013-06-25 | Wayne State University | Restoration of visual responses by in vivo delivery of rhodopsin nucleic acids |
| 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 |
| WO2008101128A1 (en) | 2007-02-14 | 2008-08-21 | The Board Of Trustees Of The Leland Stanford Junior University | System, method and applications involving identification of biological circuits such as neurological characteristics |
| WO2008106694A2 (en) | 2007-03-01 | 2008-09-04 | The Board Of Trustees Of The Leland Stanford Junior University | Systems, methods and compositions for optical stimulation of target cells |
| 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 |
| SG189813A1 (en) | 2008-04-23 | 2013-05-31 | Univ Leland Stanford Junior | Systems, methods and compositions for optical stimulation of target cells |
| JP5890176B2 (ja) | 2008-05-29 | 2016-03-22 | 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 | セカンドメッセンジャーを光制御するためのセルライン、システム、および方法 |
| AU2009260029B2 (en) | 2008-06-17 | 2016-03-17 | 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 |
| EP2303405A4 (en) | 2008-06-17 | 2017-12-27 | The Board of Trustees of the Leland Stanford Junior University | Apparatus and methods for controlling cellular development |
| 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 |
| NZ602416A (en) | 2008-11-14 | 2014-08-29 | Univ Leland Stanford Junior | Optically-based stimulation of target cells and modifications thereto |
| JP5866332B2 (ja) | 2010-03-17 | 2016-02-17 | 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 | 感光性イオンを通過させる分子 |
| US9453241B2 (en) | 2010-05-04 | 2016-09-27 | Wayne State University | AAV-mediated subcellular targeting of heterologous rhodopsins in retinal ganglion cells |
| WO2012061681A1 (en) | 2010-11-05 | 2012-05-10 | The Board Of Trustees Of The Leland Stanford Junior University. | Control and characterization of memory function |
| CN103491770B (zh) | 2010-11-05 | 2016-06-08 | 斯坦福大学托管董事会 | 稳定阶跃函数视蛋白及其使用方法 |
| US9992981B2 (en) | 2010-11-05 | 2018-06-12 | The Board Of Trustees Of The Leland Stanford Junior University | Optogenetic control of reward-related behaviors |
| CA2817175C (en) | 2010-11-05 | 2019-09-24 | The Board Of Trustees Of The Leland Stanford Junior University | Upconversion of light using lanthanide-doped nanoparticles for use in optogenetic methods |
| 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 |
| CN106106368A (zh) | 2010-11-05 | 2016-11-16 | 斯坦福大学托管董事会 | 光控cns功能障碍 |
| US8696722B2 (en) | 2010-11-22 | 2014-04-15 | The Board Of Trustees Of The Leland Stanford Junior University | Optogenetic magnetic resonance imaging |
| EP3524676A1 (en) | 2011-12-16 | 2019-08-14 | The Board of Trustees of The Leland Stanford Junior University | Opsin polypeptides and methods of use thereof |
| ES2628006T3 (es) | 2012-02-21 | 2017-08-01 | Circuit Therapeutics, Inc. | Composiciones para el tratamiento de trastornos neurogénicos del suelo pélvico |
| CN111378020A (zh) * | 2012-03-05 | 2020-07-07 | 韦恩州立大学 | 通道视蛋白-2(Chop2)突变的鉴定及使用方法 |
| 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 |
| WO2014179331A2 (en) | 2013-04-29 | 2014-11-06 | The Board Of Trustees Of The Leland Stanford Junior University | Devices, systems and methods for optogenetic modulation of action potentials in target cells |
| CA2921221A1 (en) | 2013-08-14 | 2015-02-19 | The Board Of Trustees Of The Leland Stanford Junior University | Compositions and methods for controlling pain |
| JP6118239B2 (ja) | 2013-11-29 | 2017-04-19 | 雅敏 堀 | 害虫の防除方法及び防除装置 |
| EP3102290A1 (en) | 2014-02-07 | 2016-12-14 | Massachusetts Institute Of Technology | Blue light-activated ion channel molecules and uses thereof |
| WO2015142984A1 (en) * | 2014-03-18 | 2015-09-24 | Washington University | Methods and compositions for red-shifted chromophore substitution for optogenetic applications |
| WO2015161308A1 (en) * | 2014-04-18 | 2015-10-22 | Massachusetts Institute Of Technology | Mutant channelrhodopsins with altered ion selectivity |
| WO2016209654A1 (en) | 2015-06-22 | 2016-12-29 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and devices for imaging and/or optogenetic control of light-responsive neurons |
| JP2019522469A (ja) * | 2016-06-03 | 2019-08-15 | マックス−プランク−ゲゼルシャフト ツア フェルデルンク デア ヴィッセンシャフテン エー．ファウ． | チャネルロドプシンの変異型光誘導性イオンチャネル |
| WO2017207761A1 (en) | 2016-06-03 | 2017-12-07 | Max-Planck-Gesellschaft Zur Foerderung Der Wissenschaften E.V. | Mutant light-inducible ion channel of chrimson |
| WO2018106369A2 (en) | 2016-11-06 | 2018-06-14 | Nanoscope Technologies Llc | Optogenetic modulation by multi-characteristic opsins for vision restoration and other applications thereof |
| 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 |
| WO2018189247A1 (en) * | 2017-04-12 | 2018-10-18 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | New optogenetic tool |
| CN110483645B (zh) * | 2018-05-14 | 2023-05-12 | 郑州大学第一附属医院 | 线粒体定位质子泵型视紫红质、其突变蛋白及其应用 |
| GB2586751B (en) * | 2018-07-26 | 2022-12-07 | Council Scient Ind Res | Screening kit for detection of grades of cervical cancer and process for the preparation thereof |
| WO2020054868A1 (ja) * | 2018-09-14 | 2020-03-19 | 国立大学法人名古屋工業大学 | 光応答性タンパク質及びその利用 |
| JP7723983B2 (ja) * | 2020-03-13 | 2025-08-15 | 国立大学法人 名古屋工業大学 | 色認識のための光応答性タンパク質及びその利用 |
| WO2022176754A1 (ja) * | 2021-02-18 | 2022-08-25 | 国立大学法人名古屋工業大学 | 青色光もしくは藍色光応答性タンパク質及びその利用 |
| EP4223768A1 (en) | 2022-02-04 | 2023-08-09 | Georg-August-Universität Göttingen Stiftung Öffentlichen Rechts, Universitätsmedizin | Novel mutant bacteriorhodopsin-like-channelrhodopsin ion channel |
| WO2024092248A1 (en) * | 2022-10-28 | 2024-05-02 | The Board Of Trustees Of The Leland Stanford Junior University | Enhanced light gated potassium selective channelrhodopsin |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2112510A1 (de) * | 2008-04-22 | 2009-10-28 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Verwendung von biologischen Photorezeptoren als direkt lichtgesteuerte lonenkanäle |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2112501A1 (de) | 1998-02-05 | 2009-10-28 | Novartis Ag | Verfahren und Vorrichtung zur Lumineszenzmessung |
| DE10216005A1 (de) | 2002-04-11 | 2003-10-30 | Max Planck Gesellschaft | Verwendung von biologischen Photorezeptoren als direkt lichtgesteuerte Ionenkanäle |
| US8470790B2 (en) * | 2006-05-04 | 2013-06-25 | Wayne State University | Restoration of visual responses by in vivo delivery of rhodopsin nucleic acids |
| NZ602416A (en) * | 2008-11-14 | 2014-08-29 | Univ Leland Stanford Junior | Optically-based stimulation of target cells and modifications thereto |
-
2011
- 2011-09-08 SI SI201130552T patent/SI2614079T1/sl unknown
- 2011-09-08 WO PCT/EP2011/065510 patent/WO2012032103A1/en not_active Ceased
- 2011-09-08 EP EP11760432.2A patent/EP2614079B1/en active Active
- 2011-09-08 PT PT117604322T patent/PT2614079E/pt unknown
- 2011-09-08 AU AU2011298745A patent/AU2011298745B2/en active Active
- 2011-09-08 KR KR1020137008660A patent/KR101945962B1/ko active Active
- 2011-09-08 ES ES11760432.2T patent/ES2545992T3/es active Active
- 2011-09-08 CA CA2810757A patent/CA2810757C/en active Active
- 2011-09-08 HR HRP20150846TT patent/HRP20150846T1/hr unknown
- 2011-09-08 PL PL11760432T patent/PL2614079T3/pl unknown
- 2011-09-08 HU HUE11760432A patent/HUE025952T2/en unknown
- 2011-09-08 SG SG2013016332A patent/SG188409A1/en unknown
- 2011-09-08 US US13/821,353 patent/US8748578B2/en active Active
- 2011-09-08 MX MX2013002591A patent/MX347453B/es active IP Right Grant
- 2011-09-08 DK DK11760432.2T patent/DK2614079T3/en active
- 2011-09-08 RU RU2013115454/10A patent/RU2595384C2/ru active
- 2011-09-08 CN CN201180052156.9A patent/CN103261219B/zh active Active
- 2011-09-08 BR BR112013005634A patent/BR112013005634A2/pt not_active Application Discontinuation
- 2011-09-08 JP JP2013527595A patent/JP5933556B2/ja active Active
-
2013
- 2013-03-05 IL IL225060A patent/IL225060A/en active IP Right Grant
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2112510A1 (de) * | 2008-04-22 | 2009-10-28 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Verwendung von biologischen Photorezeptoren als direkt lichtgesteuerte lonenkanäle |
Non-Patent Citations (1)
| Title |
|---|
| BAMANN C. et al, Structural guidance of the photocycle of channelrhodopsin-2 by an interhelical hydrogen bond, Biochemistery, 2010 Jan., 49 (2), abstract. PMID:20000562. * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US12234267B2 (en) | 2016-08-29 | 2025-02-25 | Wayne State University | Identification of mutations in channelopsin variants having improved light sensitivity and methods of use thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2013544494A (ja) | 2013-12-19 |
| US20130281379A1 (en) | 2013-10-24 |
| AU2011298745A1 (en) | 2013-03-21 |
| PL2614079T3 (pl) | 2016-01-29 |
| HUE025952T2 (en) | 2016-04-28 |
| AU2011298745B2 (en) | 2015-05-07 |
| CA2810757A1 (en) | 2012-03-15 |
| EP2614079A1 (en) | 2013-07-17 |
| CA2810757C (en) | 2020-06-09 |
| PT2614079E (pt) | 2015-10-06 |
| MX2013002591A (es) | 2013-07-22 |
| US8748578B2 (en) | 2014-06-10 |
| IL225060A (en) | 2016-10-31 |
| CN103261219B (zh) | 2017-05-17 |
| SG188409A1 (en) | 2013-04-30 |
| RU2013115454A (ru) | 2014-10-20 |
| EP2614079B1 (en) | 2015-07-15 |
| HRP20150846T1 (hr) | 2015-09-11 |
| JP5933556B2 (ja) | 2016-06-15 |
| ES2545992T3 (es) | 2015-09-17 |
| DK2614079T3 (en) | 2015-08-10 |
| MX347453B (es) | 2017-04-27 |
| WO2012032103A1 (en) | 2012-03-15 |
| BR112013005634A2 (pt) | 2017-06-27 |
| CN103261219A (zh) | 2013-08-21 |
| KR20130108335A (ko) | 2013-10-02 |
| SI2614079T1 (sl) | 2015-10-30 |
| KR101945962B1 (ko) | 2019-02-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2595384C2 (ru) | Мутантный канальный родопсин-2 | |
| Kleinlogel et al. | Ultra light-sensitive and fast neuronal activation with the Ca2+-permeable channelrhodopsin CatCh | |
| US7144733B2 (en) | Bio-synthetic photostimulators and methods of use | |
| Sugiyama et al. | Photocurrent attenuation by a single polar-to-nonpolar point mutation of channelrhodopsin-2 | |
| KR20110018924A (ko) | 세포주, 2차 전달물질의 광학적 조절을 위한 시스템 및 방법 | |
| Berlin et al. | Optical control of glutamate receptors of the NMDA-kind in mammalian neurons, with the use of photoswitchable ligands | |
| US20190218256A1 (en) | Mutant light-inducible ion channel of channelrhodopsin | |
| Sonnemann et al. | cAMP-induced changes in the cytosolic free Ca2+ concentration in Dictyostelium discoideum are light sensitive | |
| US11384132B2 (en) | Mutant light-inducible ion channel of chrimson | |
| JP2020516295A (ja) | 新規光遺伝学ツール | |
| Kleinlogel et al. | Ultra light-sensitive and fast neuronal activation with the Ca permeable Channelrhodopsin CatCh | |
| Hayward | Optogenetic Control and Monitoring of Ion Transport in Cells | |
| Meijer | Genetically encoded optical control of protein function | |
| Jagadish | Activity Dependent Trans-synaptic Tracing Of Neural Circuits In Drosophila |