DK2614079T3 - Mutant channelrhodopsin 2 - Google Patents
Mutant channelrhodopsin 2 Download PDFInfo
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- DK2614079T3 DK2614079T3 DK11760432.2T DK11760432T DK2614079T3 DK 2614079 T3 DK2614079 T3 DK 2614079T3 DK 11760432 T DK11760432 T DK 11760432T DK 2614079 T3 DK2614079 T3 DK 2614079T3
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Classifications
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- 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
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- 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
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- 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
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- 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
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- 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
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- 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
Claims (17)
1. Lysinducerbar ionkanal, hvor den lysinducerbare ionkanal omfatter en aminosyresekvens som har mindst 70% homologi til aminosyresekvensen vist i positionerne 1-309 af SEQ ID NO: 1 (CHOP-2), og som omfatter en substitution på en position svarende til L132 i SEQ ID NO: 1, hvilken substitution forøger polariteten af kanalen, og hvor ledningsevnen for calcium af den lysinducerbare ionkanal er forøget mindst to-fold, sammenlignet med wt CHOP-2, som bestemt ved Fura-2-billeddannelse på HEK293-celler.
2. Den lysinducerbare ionkanal ifølge krav 1, hvor den lysinducerbare ionkanal omfatter, fortrinsvis består af aminosyresekvensen vist i positionerne 1-309 af SEQ ID NO: 1 (CHOP-2), bortset fra en substitution på position L132, hvor substitutionen forøger polariteten af kanalen.
3. Den lysinducerbare ionkanal ifølge krav 1 eller 2, hvor substitutionen er valgt fra L132C, L132S, L132E, L132D, og L132T, fortrinsvis hvor substitutionen er L132C.
4. Den lysinducerbare ionkanal ifølge et hvilket som helst af de foregående krav, hvor (a) lysfølsomheden er forøget med mere end 5 gange, fortrinsvis med mere end 10 gange, mere fortrinsvis med mere end 20 gange, såsom 30 gange, endnu mere fortrinsvis med mere end 40 gange, såsom 50 gange, og mest fortrinsvis med mere end 60 gange, eller med endnu mere end 70 gange, som sammenlignet med wt CHOP-2 i hippocampus neuroner; og/eller (b) ledningsevnen for calcium er forøget mindst tre-fold, mere fortrinsvis mindst fire-fold sammenlignet med wt CHOP-2, som bestemt ved Fura-2-billeddannelse på HEK293-celler; og/eller (c) stimuleringsfrekvensen er forøget mindst 1,5-fold, mere fortrinsvis tofold, eller endnu mere fortrinsvis 2,5-fold, sammenlignet med wt CHOP-2 som bestemt med helcelle elektrofysiologiske målinger i hippocampus neuroner.
5. Den lysinducerbare ionkanal ifølge et hvilket som helst af de foregående krav, hvor den lysinducerbare ionkanal yderligere omfatter mindst en af de følgende aminosyrerester: asparaginsyre på en position tilsvarende position 253 af SEQ ID NO: 1; lysin på en position tilsvarende position 257 af SEQ ID NO: 1; tryptofan på en position tilsvarende position 260 af SEQ ID NO: 1; glutaminsyre på en position tilsvarende position 123 af SEQ ID NO: 1; histidin eller arginin, fortrinsvis arginin, på en position tilsvarende position 134 af SEQ ID NO: 1; threonin, serin, eller alanin på en position tilsvarende position 128 af SEQ ID NO: 1; og/eller alanin på en position tilsvarende position 156 af SEQ ID NO: 1.
6. Den lysinducerbare ionkanal ifølge et hvilket som helst af de foregående krav, hvor den lysinducerbare ionkanal omfatter konsensusmotivet L(I)DxxxKxxW(F,Y).
7. Channelrhodopsin, omfattende den lysinducerbare ionkanal ifølge kravene 1-6 og et retinal eller retinalderivat, fortrinsvis hvor retinalderivatet er valgt fra gruppen bestående af 3,4-dehydroretinal, 13-ethylretinal, 9-dm-retinal, 3-hydroxyretinal, 4-hydroxyretinal, naphthylretinal; 3,7,11 -trimethyl-dodeca-2,4,6,8, 10- pentaenal; 3,7-dimethyl-deca-2,4,6,8-tetraenal; 3 ,7-dimethyl-octa-2,4,6-trienal; og 6-7 rotationsblokerede retinaler, 8-9 rotationsblokerede retinaler, og 10-11 rotationsblokerede retinaler.
8. Nukleinsyresammensætning omfattende en nukleotidsekvens som koder for den lysinducerbare ionkanal ifølge et hvilket som helst af kravene 1-6.
9. Ekspressionsvektor omfattende en nukleotidsekvens som koder for den lysinducerbare ionkanal ifølge et hvilket som helst af kravene 1-6 eller nukleinsyresammensætningen ifølge krav 8, fortrinsvis hvor vektoren er egnet til genterapi, i særdeleshed hvor vektoren er egnet til virus-medieret genoverførsel.
10. Celle omfattende channelrhodopsinen ifølge krav 7, nukleinsyresammensætningen ifølge krav 8 eller ekspressionsvektoren ifølge krav 9.
11. Cellen ifølge krav 10, hvor cellen er en pattedyrscelle eller en insektcelle, eller hvor cellen er en gærcelle, fortrinsvis fra Saccharomyces cerevisiae, Schizosaccharomyces pombe, eller Pichia pastoris.
12. Cellen ifølge krav 11, hvor pattedyrscellen er (a) en fotoreceptor celle, en retinal stavcelle, en retinal tapcelle, en retinal gangliecelle, en bipolær neuron, en gangliecelle, en pseudounipolær neuron, en multipolær neuron, en pyramidal neuron, en Purkinje celle, eller en granulcelle; eller (b) en melanomcelle, en COS-celle; en BHK-celle; en HEK293-celle; en CHO-celle; en myelomcelle; eller en MDCK-celle.
13. Den lysinducerbare ionkanal ifølge kravene 1-6, eller the channelrhodopsin ifølge krav 7, eller nukleinsyresammensætningen ifølge krav 8, eller ekspressionsvektoren ifølge krav 9, eller cellen ifølge krav 10 til anvendelse som et lægemiddel.
14. Ekspressionsvektoren ifølge krav 10 til anvendelse i genterapi.
15. Den lysinducerbare ionkanal ifølge kravene 1-6, eller channelrhodopsinen ifølge krav 7, eller nukleinsyresammensætningen ifølge krav 8, eller ekspressionsvektoren ifølge krav 9, eller cellen ifølge krav 10 til anvendelse i behandlingen af blindhed eller nedsat syn.
16. Den lysinducerbare ionkanal ifølge krav 5 havende threonin, serin eller alanin på en position svarende til position 128 af SEQ ID NO: 1; og/eller alanin på en position svarende til position 156 af SEQ ID NO: 1, til anvendelse i fjernelsen af cancerceller, fortrinsvis hvor cancercellerne er melanom cancerceller.
17. Anvendelse afen lysinducerbar ionkanal ifølge kravene 1-6, eller en channelrhodopsin ifølge krav 7, eller en celle ifølge krav 10 i high-throughput screening.
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| PCT/EP2011/065510 WO2012032103A1 (en) | 2010-09-08 | 2011-09-08 | Mutant channelrhodopsin 2 |
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| CN101484005A (zh) * | 2006-05-04 | 2009-07-15 | 韦恩州立大学 | 通过向体内递送视紫红质核酸恢复视觉响应 |
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| NZ602416A (en) * | 2008-11-14 | 2014-08-29 | Univ Leland Stanford Junior | Optically-based stimulation of target cells and modifications thereto |
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| KR101945962B1 (ko) | 2019-02-08 |
| WO2012032103A1 (en) | 2012-03-15 |
| SI2614079T1 (sl) | 2015-10-30 |
| PL2614079T3 (pl) | 2016-01-29 |
| CN103261219B (zh) | 2017-05-17 |
| JP2013544494A (ja) | 2013-12-19 |
| US8748578B2 (en) | 2014-06-10 |
| CA2810757A1 (en) | 2012-03-15 |
| US20130281379A1 (en) | 2013-10-24 |
| AU2011298745A1 (en) | 2013-03-21 |
| BR112013005634A2 (pt) | 2017-06-27 |
| EP2614079B1 (en) | 2015-07-15 |
| SG188409A1 (en) | 2013-04-30 |
| HRP20150846T1 (hr) | 2015-09-11 |
| RU2013115454A (ru) | 2014-10-20 |
| CN103261219A (zh) | 2013-08-21 |
| RU2595384C2 (ru) | 2016-08-27 |
| PT2614079E (pt) | 2015-10-06 |
| CA2810757C (en) | 2020-06-09 |
| KR20130108335A (ko) | 2013-10-02 |
| JP5933556B2 (ja) | 2016-06-15 |
| MX2013002591A (es) | 2013-07-22 |
| IL225060A (en) | 2016-10-31 |
| HUE025952T2 (en) | 2016-04-28 |
| AU2011298745B2 (en) | 2015-05-07 |
| MX347453B (es) | 2017-04-27 |
| ES2545992T3 (es) | 2015-09-17 |
| EP2614079A1 (en) | 2013-07-17 |
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