CA2575994A1 - Optimizing expression of active botulinum toxin type a - Google Patents
Optimizing expression of active botulinum toxin type a Download PDFInfo
- Publication number
- CA2575994A1 CA2575994A1 CA002575994A CA2575994A CA2575994A1 CA 2575994 A1 CA2575994 A1 CA 2575994A1 CA 002575994 A CA002575994 A CA 002575994A CA 2575994 A CA2575994 A CA 2575994A CA 2575994 A1 CA2575994 A1 CA 2575994A1
- Authority
- CA
- Canada
- Prior art keywords
- open reading
- reading frame
- cell
- seq
- active bont
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 230000014509 gene expression Effects 0.000 title claims abstract description 775
- 108010057266 Type A Botulinum Toxins Proteins 0.000 title description 2
- 229940094657 botulinum toxin type a Drugs 0.000 title description 2
- 108700026244 Open Reading Frames Proteins 0.000 claims abstract description 791
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 505
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 496
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 496
- 230000001965 increasing effect Effects 0.000 claims abstract description 340
- 101710117542 Botulinum neurotoxin type A Proteins 0.000 claims abstract description 164
- 210000004027 cell Anatomy 0.000 claims description 1043
- 239000002773 nucleotide Substances 0.000 claims description 227
- 125000003729 nucleotide group Chemical group 0.000 claims description 227
- 239000013604 expression vector Substances 0.000 claims description 190
- 108020004705 Codon Proteins 0.000 claims description 183
- 241000238631 Hexapoda Species 0.000 claims description 95
- 210000004962 mammalian cell Anatomy 0.000 claims description 76
- 210000001236 prokaryotic cell Anatomy 0.000 claims description 51
- 241000283690 Bos taurus Species 0.000 claims description 46
- 241000283073 Equus caballus Species 0.000 claims description 46
- 241000288906 Primates Species 0.000 claims description 43
- 241000588724 Escherichia coli Species 0.000 claims description 41
- 241000699800 Cricetinae Species 0.000 claims description 40
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims description 38
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 claims description 38
- 210000005253 yeast cell Anatomy 0.000 claims description 38
- 241001112696 Clostridia Species 0.000 claims description 24
- 210000005260 human cell Anatomy 0.000 claims description 23
- 241000235058 Komagataella pastoris Species 0.000 claims description 22
- 241000256251 Spodoptera frugiperda Species 0.000 claims description 19
- 230000009465 prokaryotic expression Effects 0.000 claims description 19
- 241000255601 Drosophila melanogaster Species 0.000 claims description 16
- 241000255908 Manduca sexta Species 0.000 claims description 16
- 241001452677 Ogataea methanolica Species 0.000 claims description 16
- 241000255993 Trichoplusia ni Species 0.000 claims description 14
- 241000235015 Yarrowia lipolytica Species 0.000 claims description 13
- 241000194108 Bacillus licheniformis Species 0.000 claims description 12
- 235000014469 Bacillus subtilis Nutrition 0.000 claims description 12
- 241000606124 Bacteroides fragilis Species 0.000 claims description 12
- 241000010804 Caulobacter vibrioides Species 0.000 claims description 12
- 241000589308 Methylobacterium extorquens Species 0.000 claims description 12
- 241000320412 Ogataea angusta Species 0.000 claims description 12
- 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 claims description 12
- 244000057717 Streptococcus lactis Species 0.000 claims description 12
- 241000589540 Pseudomonas fluorescens Species 0.000 claims description 11
- 244000063299 Bacillus subtilis Species 0.000 claims description 10
- 241000588653 Neisseria Species 0.000 claims description 10
- 241000235347 Schizosaccharomyces pombe Species 0.000 claims description 10
- 235000014897 Streptococcus lactis Nutrition 0.000 claims description 10
- 238000000034 method Methods 0.000 abstract description 166
- 150000001413 amino acids Chemical class 0.000 description 152
- 235000001014 amino acid Nutrition 0.000 description 148
- 108090000765 processed proteins & peptides Proteins 0.000 description 96
- 230000027455 binding Effects 0.000 description 89
- 108090000623 proteins and genes Proteins 0.000 description 69
- 108030001720 Bontoxilysin Proteins 0.000 description 51
- 102000004169 proteins and genes Human genes 0.000 description 42
- 230000001404 mediated effect Effects 0.000 description 39
- 239000013612 plasmid Substances 0.000 description 39
- 239000013598 vector Substances 0.000 description 37
- 230000007017 scission Effects 0.000 description 36
- 238000003776 cleavage reaction Methods 0.000 description 35
- 235000018102 proteins Nutrition 0.000 description 35
- 241000196324 Embryophyta Species 0.000 description 34
- 241000699666 Mus <mouse, genus> Species 0.000 description 32
- 241000700159 Rattus Species 0.000 description 32
- 230000008859 change Effects 0.000 description 31
- 229920002704 polyhistidine Polymers 0.000 description 31
- 108700010070 Codon Usage Proteins 0.000 description 30
- 108091008146 restriction endonucleases Proteins 0.000 description 29
- 241000251468 Actinopterygii Species 0.000 description 28
- 102000004196 processed proteins & peptides Human genes 0.000 description 25
- 241000282414 Homo sapiens Species 0.000 description 24
- 230000003612 virological effect Effects 0.000 description 23
- 231100001102 clostridial toxin Toxicity 0.000 description 22
- 230000010076 replication Effects 0.000 description 22
- 108091034117 Oligonucleotide Proteins 0.000 description 19
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 19
- 210000003527 eukaryotic cell Anatomy 0.000 description 19
- 239000012634 fragment Substances 0.000 description 19
- 108020004414 DNA Proteins 0.000 description 18
- 108091005804 Peptidases Proteins 0.000 description 18
- 239000004365 Protease Substances 0.000 description 17
- 102100038132 Endogenous retrovirus group K member 6 Pro protein Human genes 0.000 description 16
- 230000000670 limiting effect Effects 0.000 description 16
- 235000019419 proteases Nutrition 0.000 description 16
- 230000001105 regulatory effect Effects 0.000 description 16
- 239000003053 toxin Substances 0.000 description 15
- 231100000765 toxin Toxicity 0.000 description 15
- 108700012359 toxins Proteins 0.000 description 15
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 14
- 231100001103 botulinum neurotoxin Toxicity 0.000 description 14
- 238000004113 cell culture Methods 0.000 description 14
- 239000000284 extract Substances 0.000 description 14
- 229940053031 botulinum toxin Drugs 0.000 description 13
- 241000894006 Bacteria Species 0.000 description 12
- 108091035707 Consensus sequence Proteins 0.000 description 12
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 12
- 239000002581 neurotoxin Substances 0.000 description 12
- 231100000618 neurotoxin Toxicity 0.000 description 12
- 102000005962 receptors Human genes 0.000 description 12
- 108020003175 receptors Proteins 0.000 description 12
- 241000894007 species Species 0.000 description 12
- 238000001890 transfection Methods 0.000 description 11
- 238000012546 transfer Methods 0.000 description 11
- 241000193155 Clostridium botulinum Species 0.000 description 10
- 108091028043 Nucleic acid sequence Proteins 0.000 description 10
- 239000003153 chemical reaction reagent Substances 0.000 description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
- 230000003957 neurotransmitter release Effects 0.000 description 10
- 241000287828 Gallus gallus Species 0.000 description 9
- 241000269457 Xenopus tropicalis Species 0.000 description 9
- 238000013459 approach Methods 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 208000035475 disorder Diseases 0.000 description 9
- 238000003752 polymerase chain reaction Methods 0.000 description 9
- 230000001177 retroviral effect Effects 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- 238000002560 therapeutic procedure Methods 0.000 description 9
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 8
- 102100031077 Calcineurin B homologous protein 3 Human genes 0.000 description 8
- 101100007328 Cocos nucifera COS-1 gene Proteins 0.000 description 8
- 101000777270 Homo sapiens Calcineurin B homologous protein 3 Proteins 0.000 description 8
- 241000209510 Liliopsida Species 0.000 description 8
- 241001233957 eudicotyledons Species 0.000 description 8
- 230000001939 inductive effect Effects 0.000 description 8
- 238000010369 molecular cloning Methods 0.000 description 8
- 238000006467 substitution reaction Methods 0.000 description 8
- 238000010361 transduction Methods 0.000 description 8
- 230000026683 transduction Effects 0.000 description 8
- 238000011282 treatment Methods 0.000 description 8
- 241000701161 unidentified adenovirus Species 0.000 description 8
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 7
- 241000168726 Dictyostelium discoideum Species 0.000 description 7
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 7
- 241000701832 Enterobacteria phage T3 Species 0.000 description 7
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 7
- 101710138657 Neurotoxin Proteins 0.000 description 7
- 108010029485 Protein Isoforms Proteins 0.000 description 7
- 102000001708 Protein Isoforms Human genes 0.000 description 7
- 240000008042 Zea mays Species 0.000 description 7
- MZVQCMJNVPIDEA-UHFFFAOYSA-N [CH2]CN(CC)CC Chemical group [CH2]CN(CC)CC MZVQCMJNVPIDEA-UHFFFAOYSA-N 0.000 description 7
- 235000004279 alanine Nutrition 0.000 description 7
- 238000003556 assay Methods 0.000 description 7
- 238000004422 calculation algorithm Methods 0.000 description 7
- 230000002255 enzymatic effect Effects 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- 230000035772 mutation Effects 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- 241000282552 Chlorocebus aethiops Species 0.000 description 6
- 101000933563 Clostridium botulinum Botulinum neurotoxin type G Proteins 0.000 description 6
- 101000985023 Clostridium botulinum C phage Botulinum neurotoxin type C Proteins 0.000 description 6
- 241000699802 Cricetulus griseus Species 0.000 description 6
- 101100440639 Drosophila melanogaster Cont gene Proteins 0.000 description 6
- 241000713666 Lentivirus Species 0.000 description 6
- 241000699660 Mus musculus Species 0.000 description 6
- 241000588650 Neisseria meningitidis Species 0.000 description 6
- 208000002193 Pain Diseases 0.000 description 6
- 102000005917 R-SNARE Proteins Human genes 0.000 description 6
- 108010005730 R-SNARE Proteins Proteins 0.000 description 6
- 241000700157 Rattus norvegicus Species 0.000 description 6
- 108010083644 Ribonucleases Proteins 0.000 description 6
- 102000006382 Ribonucleases Human genes 0.000 description 6
- 241000282898 Sus scrofa Species 0.000 description 6
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 6
- 235000007244 Zea mays Nutrition 0.000 description 6
- 230000001580 bacterial effect Effects 0.000 description 6
- 239000001506 calcium phosphate Substances 0.000 description 6
- 229910000389 calcium phosphate Inorganic materials 0.000 description 6
- 235000011010 calcium phosphates Nutrition 0.000 description 6
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 6
- 238000012217 deletion Methods 0.000 description 6
- 230000037430 deletion Effects 0.000 description 6
- 238000004520 electroporation Methods 0.000 description 6
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 6
- 230000035987 intoxication Effects 0.000 description 6
- 231100000566 intoxication Toxicity 0.000 description 6
- 210000002569 neuron Anatomy 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 230000005030 transcription termination Effects 0.000 description 6
- 230000005945 translocation Effects 0.000 description 6
- 238000012384 transportation and delivery Methods 0.000 description 6
- 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 6
- 241001515965 unidentified phage Species 0.000 description 6
- 241000219195 Arabidopsis thaliana Species 0.000 description 5
- 239000004475 Arginine Substances 0.000 description 5
- 101710117515 Botulinum neurotoxin type E Proteins 0.000 description 5
- 101710117520 Botulinum neurotoxin type F Proteins 0.000 description 5
- 241000252212 Danio rerio Species 0.000 description 5
- 229920002307 Dextran Polymers 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 229920002873 Polyethylenimine Polymers 0.000 description 5
- 102000000583 SNARE Proteins Human genes 0.000 description 5
- 108010041948 SNARE Proteins Proteins 0.000 description 5
- 241000700584 Simplexvirus Species 0.000 description 5
- 108010055044 Tetanus Toxin Proteins 0.000 description 5
- 241000723792 Tobacco etch virus Species 0.000 description 5
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000002537 cosmetic Substances 0.000 description 5
- 235000018417 cysteine Nutrition 0.000 description 5
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 5
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 238000001476 gene delivery Methods 0.000 description 5
- 230000007246 mechanism Effects 0.000 description 5
- 238000000520 microinjection Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 238000001668 nucleic acid synthesis Methods 0.000 description 5
- 230000008488 polyadenylation Effects 0.000 description 5
- 238000010186 staining Methods 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 230000014616 translation Effects 0.000 description 5
- 241000701447 unidentified baculovirus Species 0.000 description 5
- 241001430294 unidentified retrovirus Species 0.000 description 5
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 4
- 101710117524 Botulinum neurotoxin type B Proteins 0.000 description 4
- 101000985020 Clostridium botulinum D phage Botulinum neurotoxin type D Proteins 0.000 description 4
- 102000053602 DNA Human genes 0.000 description 4
- 229920000209 Hexadimethrine bromide Polymers 0.000 description 4
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 4
- 241001599018 Melanogaster Species 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 241001582326 Renia Species 0.000 description 4
- 108030001722 Tentoxilysin Proteins 0.000 description 4
- 206010043376 Tetanus Diseases 0.000 description 4
- 241000209140 Triticum Species 0.000 description 4
- 235000021307 Triticum Nutrition 0.000 description 4
- 241000269368 Xenopus laevis Species 0.000 description 4
- 230000006229 amino acid addition Effects 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 238000010367 cloning Methods 0.000 description 4
- 230000000295 complement effect Effects 0.000 description 4
- 238000010276 construction Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000001502 gel electrophoresis Methods 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 150000002632 lipids Chemical class 0.000 description 4
- 238000002887 multiple sequence alignment Methods 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 238000001243 protein synthesis Methods 0.000 description 4
- 239000007790 solid phase Substances 0.000 description 4
- 230000001052 transient effect Effects 0.000 description 4
- 230000004572 zinc-binding Effects 0.000 description 4
- 229930024421 Adenine Natural products 0.000 description 3
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 3
- 108010025188 Alcohol oxidase Proteins 0.000 description 3
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 3
- 241001112695 Clostridiales Species 0.000 description 3
- 241000701022 Cytomegalovirus Species 0.000 description 3
- 206010019233 Headaches Diseases 0.000 description 3
- 239000006142 Luria-Bertani Agar Substances 0.000 description 3
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 3
- 108010039918 Polylysine Proteins 0.000 description 3
- 108010010469 Qa-SNARE Proteins Proteins 0.000 description 3
- 102000050389 Syntaxin Human genes 0.000 description 3
- 108020004566 Transfer RNA Proteins 0.000 description 3
- 244000098338 Triticum aestivum Species 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 229960000643 adenine Drugs 0.000 description 3
- 230000004075 alteration Effects 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 3
- 108010006025 bovine growth hormone Proteins 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 3
- 210000000805 cytoplasm Anatomy 0.000 description 3
- 229940104302 cytosine Drugs 0.000 description 3
- 239000000975 dye Substances 0.000 description 3
- 230000004927 fusion Effects 0.000 description 3
- 238000001415 gene therapy Methods 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 3
- 231100000869 headache Toxicity 0.000 description 3
- 238000001597 immobilized metal affinity chromatography Methods 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 238000002372 labelling Methods 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 238000002703 mutagenesis Methods 0.000 description 3
- 231100000350 mutagenesis Toxicity 0.000 description 3
- 208000018360 neuromuscular disease Diseases 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- 230000002093 peripheral effect Effects 0.000 description 3
- 210000002856 peripheral neuron Anatomy 0.000 description 3
- 229920000656 polylysine Polymers 0.000 description 3
- 239000013615 primer Substances 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000001742 protein purification Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 102000005969 steroid hormone receptors Human genes 0.000 description 3
- 108020003113 steroid hormone receptors Proteins 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 229940118376 tetanus toxin Drugs 0.000 description 3
- 229940104230 thymidine Drugs 0.000 description 3
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 3
- 230000011215 vesicle docking Effects 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- 102100036826 Aldehyde oxidase Human genes 0.000 description 2
- 101710131969 Aldehyde oxidase 1 Proteins 0.000 description 2
- 241000710929 Alphavirus Species 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 241000193163 Clostridioides difficile Species 0.000 description 2
- 241000193468 Clostridium perfringens Species 0.000 description 2
- 241000702421 Dependoparvovirus Species 0.000 description 2
- 108010016626 Dipeptides Proteins 0.000 description 2
- 208000017701 Endocrine disease Diseases 0.000 description 2
- 108010013369 Enteropeptidase Proteins 0.000 description 2
- 102100029727 Enteropeptidase Human genes 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 241000700662 Fowlpox virus Species 0.000 description 2
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 2
- 102100034349 Integrase Human genes 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 241000713869 Moloney murine leukemia virus Species 0.000 description 2
- 241000714177 Murine leukemia virus Species 0.000 description 2
- 208000029549 Muscle injury Diseases 0.000 description 2
- 208000016222 Pancreatic disease Diseases 0.000 description 2
- 208000018737 Parkinson disease Diseases 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- 101710182846 Polyhedrin Proteins 0.000 description 2
- 108010076504 Protein Sorting Signals Proteins 0.000 description 2
- 241000710961 Semliki Forest virus Species 0.000 description 2
- 241000710960 Sindbis virus Species 0.000 description 2
- 108010043401 Small Ubiquitin-Related Modifier Proteins Proteins 0.000 description 2
- 102000002669 Small Ubiquitin-Related Modifier Proteins Human genes 0.000 description 2
- 208000004350 Strabismus Diseases 0.000 description 2
- 241000701093 Suid alphaherpesvirus 1 Species 0.000 description 2
- 108700005078 Synthetic Genes Proteins 0.000 description 2
- 108090000190 Thrombin Proteins 0.000 description 2
- 101150050575 URA3 gene Proteins 0.000 description 2
- 241000700618 Vaccinia virus Species 0.000 description 2
- 230000001594 aberrant effect Effects 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 238000000246 agarose gel electrophoresis Methods 0.000 description 2
- 230000003698 anagen phase Effects 0.000 description 2
- 210000004102 animal cell Anatomy 0.000 description 2
- 230000003466 anti-cipated effect Effects 0.000 description 2
- 206010005159 blepharospasm Diseases 0.000 description 2
- 230000000744 blepharospasm Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 230000007248 cellular mechanism Effects 0.000 description 2
- 230000002759 chromosomal effect Effects 0.000 description 2
- 210000000349 chromosome Anatomy 0.000 description 2
- NKLPQNGYXWVELD-UHFFFAOYSA-M coomassie brilliant blue Chemical compound [Na+].C1=CC(OCC)=CC=C1NC1=CC=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C=CC(=CC=2)N(CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=C1 NKLPQNGYXWVELD-UHFFFAOYSA-M 0.000 description 2
- 239000008358 core component Substances 0.000 description 2
- 210000000172 cytosol Anatomy 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 230000028023 exocytosis Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 208000030533 eye disease Diseases 0.000 description 2
- 108020001507 fusion proteins Proteins 0.000 description 2
- 102000037865 fusion proteins Human genes 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 238000009396 hybridization Methods 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 230000000415 inactivating effect Effects 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 239000002858 neurotransmitter agent Substances 0.000 description 2
- 238000005457 optimization Methods 0.000 description 2
- 238000007858 polymerase cycling assembly Methods 0.000 description 2
- 108091033319 polynucleotide Proteins 0.000 description 2
- 102000040430 polynucleotide Human genes 0.000 description 2
- 239000002157 polynucleotide Substances 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 238000001273 protein sequence alignment Methods 0.000 description 2
- 210000001938 protoplast Anatomy 0.000 description 2
- 210000001995 reticulocyte Anatomy 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 230000002103 transcriptional effect Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- DIGQNXIGRZPYDK-WKSCXVIASA-N (2R)-6-amino-2-[[2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-[[(2R,3S)-2-[[2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S,3S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2R)-2-[[2-[[2-[[2-[(2-amino-1-hydroxyethylidene)amino]-3-carboxy-1-hydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1,5-dihydroxy-5-iminopentylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]hexanoic acid Chemical compound C[C@@H]([C@@H](C(=N[C@@H](CS)C(=N[C@@H](C)C(=N[C@@H](CO)C(=NCC(=N[C@@H](CCC(=N)O)C(=NC(CS)C(=N[C@H]([C@H](C)O)C(=N[C@H](CS)C(=N[C@H](CO)C(=NCC(=N[C@H](CS)C(=NCC(=N[C@H](CCCCN)C(=O)O)O)O)O)O)O)O)O)O)O)O)O)O)O)N=C([C@H](CS)N=C([C@H](CO)N=C([C@H](CO)N=C([C@H](C)N=C(CN=C([C@H](CO)N=C([C@H](CS)N=C(CN=C(C(CS)N=C(C(CC(=O)O)N=C(CN)O)O)O)O)O)O)O)O)O)O)O)O DIGQNXIGRZPYDK-WKSCXVIASA-N 0.000 description 1
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- 108010091324 3C proteases Proteins 0.000 description 1
- 101150096273 ADE2 gene Proteins 0.000 description 1
- 102100038740 Activator of RNA decay Human genes 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 108091093088 Amplicon Proteins 0.000 description 1
- 206010002153 Anal fissure Diseases 0.000 description 1
- 208000016583 Anus disease Diseases 0.000 description 1
- 101100437118 Arabidopsis thaliana AUG1 gene Proteins 0.000 description 1
- 208000002109 Argyria Diseases 0.000 description 1
- XFTWUNOVBCHBJR-UHFFFAOYSA-N Aspergillomarasmine A Chemical compound OC(=O)C(N)CNC(C(O)=O)CNC(C(O)=O)CC(O)=O XFTWUNOVBCHBJR-UHFFFAOYSA-N 0.000 description 1
- 102100022717 Atypical chemokine receptor 1 Human genes 0.000 description 1
- 208000008035 Back Pain Diseases 0.000 description 1
- 108010077805 Bacterial Proteins Proteins 0.000 description 1
- 208000018084 Bone neoplasm Diseases 0.000 description 1
- 208000003508 Botulism Diseases 0.000 description 1
- 101100095557 Caenorhabditis elegans ulp-1 gene Proteins 0.000 description 1
- 102000000584 Calmodulin Human genes 0.000 description 1
- 108010041952 Calmodulin Proteins 0.000 description 1
- 241000222178 Candida tropicalis Species 0.000 description 1
- 101710132601 Capsid protein Proteins 0.000 description 1
- 241000193403 Clostridium Species 0.000 description 1
- 241000193171 Clostridium butyricum Species 0.000 description 1
- 241000193449 Clostridium tetani Species 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 102000012410 DNA Ligases Human genes 0.000 description 1
- 108010061982 DNA Ligases Proteins 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 241000450599 DNA viruses Species 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 208000014094 Dystonic disease Diseases 0.000 description 1
- 102100031780 Endonuclease Human genes 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 108010059378 Endopeptidases Proteins 0.000 description 1
- 102000005593 Endopeptidases Human genes 0.000 description 1
- 101710091045 Envelope protein Proteins 0.000 description 1
- 241001198387 Escherichia coli BL21(DE3) Species 0.000 description 1
- 208000000289 Esophageal Achalasia Diseases 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 206010063006 Facial spasm Diseases 0.000 description 1
- 108010074860 Factor Xa Proteins 0.000 description 1
- 208000001640 Fibromyalgia Diseases 0.000 description 1
- 208000009531 Fissure in Ano Diseases 0.000 description 1
- 101000930822 Giardia intestinalis Dipeptidyl-peptidase 4 Proteins 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 102000005720 Glutathione transferase Human genes 0.000 description 1
- 108010070675 Glutathione transferase Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 101100246753 Halobacterium salinarum (strain ATCC 700922 / JCM 11081 / NRC-1) pyrF gene Proteins 0.000 description 1
- 208000004095 Hemifacial Spasm Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000678879 Homo sapiens Atypical chemokine receptor 1 Proteins 0.000 description 1
- 241000430519 Human rhinovirus sp. Species 0.000 description 1
- 208000008454 Hyperhidrosis Diseases 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- 208000027601 Inner ear disease Diseases 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- 244000207747 Lemna gibba Species 0.000 description 1
- 235000006438 Lemna gibba Nutrition 0.000 description 1
- 244000207740 Lemna minor Species 0.000 description 1
- 235000006439 Lemna minor Nutrition 0.000 description 1
- 208000008930 Low Back Pain Diseases 0.000 description 1
- 238000003231 Lowry assay Methods 0.000 description 1
- 238000009013 Lowry's assay Methods 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 101710175625 Maltose/maltodextrin-binding periplasmic protein Proteins 0.000 description 1
- 108010006035 Metalloproteases Proteins 0.000 description 1
- 102000005741 Metalloproteases Human genes 0.000 description 1
- 102000003792 Metallothionein Human genes 0.000 description 1
- 108090000157 Metallothionein Proteins 0.000 description 1
- 208000008238 Muscle Spasticity Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 206010030136 Oesophageal achalasia Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 241000235648 Pichia Species 0.000 description 1
- 241000709664 Picornaviridae Species 0.000 description 1
- 108700001094 Plant Genes Proteins 0.000 description 1
- 108010030975 Polyketide Synthases Proteins 0.000 description 1
- 101710188315 Protein X Proteins 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 206010040744 Sinus headache Diseases 0.000 description 1
- 206010067672 Spasmodic dysphonia Diseases 0.000 description 1
- 108091081024 Start codon Proteins 0.000 description 1
- 102000004183 Synaptosomal-Associated Protein 25 Human genes 0.000 description 1
- 108010057722 Synaptosomal-Associated Protein 25 Proteins 0.000 description 1
- 108010076818 TEV protease Proteins 0.000 description 1
- 206010043269 Tension headache Diseases 0.000 description 1
- 208000008548 Tension-Type Headache Diseases 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 208000024799 Thyroid disease Diseases 0.000 description 1
- 206010044074 Torticollis Diseases 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 101710082245 Ubiquitin-like protein 1 Proteins 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 229910052770 Uranium Inorganic materials 0.000 description 1
- 208000016599 Uterine disease Diseases 0.000 description 1
- 241000711975 Vesicular stomatitis virus Species 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 241000269370 Xenopus <genus> Species 0.000 description 1
- 108091006982 Zinc-dependent endopeptidases Proteins 0.000 description 1
- 102000036861 Zinc-dependent endopeptidases Human genes 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 201000000621 achalasia Diseases 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 150000003838 adenosines Chemical class 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 238000005377 adsorption chromatography Methods 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 238000012870 ammonium sulfate precipitation Methods 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 238000007845 assembly PCR Methods 0.000 description 1
- 238000000376 autoradiography Methods 0.000 description 1
- 230000010310 bacterial transformation Effects 0.000 description 1
- 230000000721 bacterilogical effect Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- OHJMTUPIZMNBFR-UHFFFAOYSA-N biuret Chemical compound NC(=O)NC(N)=O OHJMTUPIZMNBFR-UHFFFAOYSA-N 0.000 description 1
- 229930189065 blasticidin Natural products 0.000 description 1
- 238000010504 bond cleavage reaction Methods 0.000 description 1
- 229940089093 botox Drugs 0.000 description 1
- 206010006514 bruxism Diseases 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 102000028861 calmodulin binding Human genes 0.000 description 1
- 108091000084 calmodulin binding Proteins 0.000 description 1
- 210000000234 capsid Anatomy 0.000 description 1
- 229920006317 cationic polymer Polymers 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 210000004671 cell-free system Anatomy 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 206010008129 cerebral palsy Diseases 0.000 description 1
- 201000002866 cervical dystonia Diseases 0.000 description 1
- 230000001713 cholinergic effect Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 230000005782 double-strand break Effects 0.000 description 1
- 230000012361 double-strand break repair Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 208000010118 dystonia Diseases 0.000 description 1
- -1 e.g. Proteins 0.000 description 1
- 108010057988 ecdysone receptor Proteins 0.000 description 1
- 230000005684 electric field Effects 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 230000009144 enzymatic modification Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 201000006517 essential tremor Diseases 0.000 description 1
- 238000012869 ethanol precipitation Methods 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 238000012757 fluorescence staining Methods 0.000 description 1
- 230000037433 frameshift Effects 0.000 description 1
- 238000002825 functional assay Methods 0.000 description 1
- 150000002270 gangliosides Chemical class 0.000 description 1
- 208000021302 gastroesophageal reflux disease Diseases 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000001641 gel filtration chromatography Methods 0.000 description 1
- 239000010437 gem Substances 0.000 description 1
- 108091008053 gene clusters Proteins 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 238000004191 hydrophobic interaction chromatography Methods 0.000 description 1
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 1
- 230000037315 hyperhidrosis Effects 0.000 description 1
- 230000001660 hyperkinetic effect Effects 0.000 description 1
- 229960004716 idoxuridine Drugs 0.000 description 1
- 239000002596 immunotoxin Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 238000012804 iterative process Methods 0.000 description 1
- 230000000366 juvenile effect Effects 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 201000003890 low compliance bladder Diseases 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 210000004779 membrane envelope Anatomy 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 230000002151 myoclonic effect Effects 0.000 description 1
- 230000024717 negative regulation of secretion Effects 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 238000001821 nucleic acid purification Methods 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 229940046166 oligodeoxynucleotide Drugs 0.000 description 1
- 229940124276 oligodeoxyribonucleotide Drugs 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 208000024691 pancreas disease Diseases 0.000 description 1
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 1
- 230000008823 permeabilization Effects 0.000 description 1
- 230000002974 pharmacogenomic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229940080469 phosphocellulose Drugs 0.000 description 1
- 150000008300 phosphoramidites Chemical class 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 230000001323 posttranslational effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000001566 pro-viral effect Effects 0.000 description 1
- 102000003998 progesterone receptors Human genes 0.000 description 1
- 108090000468 progesterone receptors Proteins 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 238000002731 protein assay Methods 0.000 description 1
- 230000030788 protein refolding Effects 0.000 description 1
- 231100000654 protein toxin Toxicity 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 238000002708 random mutagenesis Methods 0.000 description 1
- 108091007054 readthrough proteins Proteins 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000004153 renaturation Methods 0.000 description 1
- 230000008263 repair mechanism Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 108090000589 ribonuclease E Proteins 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 239000010979 ruby Substances 0.000 description 1
- 229910001750 ruby Inorganic materials 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- QSHGUCSTWRSQAF-FJSLEGQWSA-N s-peptide Chemical compound C([C@@H](C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC(OS(O)(=O)=O)=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C1=CC=C(OS(O)(=O)=O)C=C1 QSHGUCSTWRSQAF-FJSLEGQWSA-N 0.000 description 1
- 238000003345 scintillation counting Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 201000002849 spasmodic dystonia Diseases 0.000 description 1
- 208000018198 spasticity Diseases 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000003153 stable transfection Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000013179 statistical model Methods 0.000 description 1
- 108010018381 streptavidin-binding peptide Proteins 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 210000000106 sweat gland Anatomy 0.000 description 1
- 230000000946 synaptic effect Effects 0.000 description 1
- 210000002504 synaptic vesicle Anatomy 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 238000012876 topography Methods 0.000 description 1
- 238000006257 total synthesis reaction Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000007888 toxin activity Effects 0.000 description 1
- 230000024033 toxin binding Effects 0.000 description 1
- 230000013715 transcription antitermination Effects 0.000 description 1
- 239000012096 transfection reagent Substances 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 230000010474 transient expression Effects 0.000 description 1
- 238000003146 transient transfection Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000012863 translational readthrough Effects 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/33—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Clostridium (G)
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US59912104P | 2004-08-04 | 2004-08-04 | |
| US60/599,121 | 2004-08-04 | ||
| PCT/US2005/027917 WO2006017749A2 (en) | 2004-08-04 | 2005-08-03 | Optimizing expression of active botulinum toxin type a |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2575994A1 true CA2575994A1 (en) | 2006-02-16 |
Family
ID=35355531
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002575994A Abandoned CA2575994A1 (en) | 2004-08-04 | 2005-08-03 | Optimizing expression of active botulinum toxin type a |
Country Status (6)
| Country | Link |
|---|---|
| US (2) | US20080057575A1 (https=) |
| EP (1) | EP1773874B1 (https=) |
| JP (1) | JP2008508886A (https=) |
| AU (1) | AU2005271372B2 (https=) |
| CA (1) | CA2575994A1 (https=) |
| WO (1) | WO2006017749A2 (https=) |
Families Citing this family (50)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7514088B2 (en) | 2005-03-15 | 2009-04-07 | Allergan, Inc. | Multivalent Clostridial toxin derivatives and methods of their use |
| US20080057575A1 (en) * | 2004-08-04 | 2008-03-06 | Allergan, Inc. | Optimizing Expression of Active Botulinum Toxin Type A |
| WO2006068794A2 (en) | 2004-11-22 | 2006-06-29 | New York University | Genetically engineered clostridial genes, proteins encoded by the engineered genes, and uses thereof |
| ATE518882T1 (de) | 2005-09-19 | 2011-08-15 | Allergan Inc | Mit clostridientoxin aktivierbare clostridientoxine |
| US8168206B1 (en) | 2005-10-06 | 2012-05-01 | Allergan, Inc. | Animal protein-free pharmaceutical compositions |
| EP2021489A2 (en) * | 2006-05-30 | 2009-02-11 | Dow Global Technologies Inc. | Codon optimization method |
| CA2693958A1 (en) | 2007-06-14 | 2008-12-18 | Emergent Biosolutions, Inc. | Chemically modified peptides with improved immunogenicity |
| CN105833254A (zh) | 2008-12-10 | 2016-08-10 | 阿勒根公司 | 梭菌毒素药物组合物 |
| EP2218783A1 (en) | 2009-02-05 | 2010-08-18 | Merz Pharma GmbH & Co. KGaA | Novel method for the manufacturing of neurotoxins |
| KR101923847B1 (ko) | 2009-03-13 | 2018-11-29 | 알러간, 인코포레이티드 | 면역 기반 재표적화된 엔도펩티다제 활성 검정 |
| SG181772A1 (en) | 2009-12-16 | 2012-07-30 | Allergan Inc | Modified clostridial toxins comprising an integrated protease cleavage site-binding domain |
| EP2528941A4 (en) * | 2010-01-25 | 2013-05-29 | Univ New York | FOR TRANSPORT STUDIES AND NEURONAL ADMINISTRATION, MANIPULATED RECOMBINANT DERIVATIVES FROM BOTULINUM NEUROTOXINES |
| JP5956350B2 (ja) | 2010-01-25 | 2016-07-27 | アラーガン、インコーポレイテッドＡｌｌｅｒｇａｎ，Ｉｎｃｏｒｐｏｒａｔｅｄ | 単鎖タンパク質をそれらの２鎖形態に細胞内変換する方法 |
| MX2013005749A (es) | 2010-11-23 | 2013-08-01 | Allergan Inc | Composiciones y metodos para producir enterocinasa en levaduras. |
| US20120244188A1 (en) | 2011-03-25 | 2012-09-27 | Allergan, Inc. | Treatment of Sensory Disturbance Disorders |
| US20120251573A1 (en) | 2011-03-28 | 2012-10-04 | Allergan, Inc. | Endopeptidase Treatment of Neuroendocrine Disorders |
| US20120251575A1 (en) | 2011-03-28 | 2012-10-04 | Allergan, Inc. | Endopeptidase Treatment of Involuntary Movement Disorders |
| US20120251574A1 (en) | 2011-03-28 | 2012-10-04 | Allergan, Inc. | Endopeptidase and Neurotoxin Combination Treatment of Multiple Medical Conditions |
| US20120251515A1 (en) | 2011-03-29 | 2012-10-04 | Allergan, Inc. | Endopeptidase Treatment of Cosmesis Disorders |
| US20120251518A1 (en) | 2011-03-29 | 2012-10-04 | Allergan, Inc. | Endopeptidase Treatment of Sexual Dysfunction Disorders |
| US20120251519A1 (en) | 2011-03-29 | 2012-10-04 | Allergan, Inc. | Endopeptidase Treatment of Smooth Muscle Disorders |
| WO2012135304A1 (en) | 2011-03-29 | 2012-10-04 | Allergan, Inc. | Vagal nerve-based disorders |
| EP2709723B1 (en) * | 2011-05-17 | 2019-11-20 | Boston Scientific Neuromodulation Corporation | User-defined graphical shapes used as a visualization aid for stimulator programming |
| WO2012174123A1 (en) | 2011-06-13 | 2012-12-20 | Allergan, Inc. | Treatment of psychological trauma |
| EP2793934B1 (en) | 2011-12-23 | 2017-08-23 | Merz Pharma GmbH & Co. KGaA | Novel method for the manufacturing of di-chain proteins for use in humans |
| US20130171122A1 (en) | 2011-12-29 | 2013-07-04 | Allergan, Inc. | Endopeptidase and neurotoxin combination treatment of bladder disorders |
| WO2014079495A1 (en) * | 2012-11-21 | 2014-05-30 | Syntaxin Limited | Methods for the manufacture of proteolytically processed polypeptides |
| US9315549B2 (en) | 2013-01-28 | 2016-04-19 | New York University | Treatment methods using atoxic neurotoxin derivatives |
| AU2014240116B2 (en) * | 2013-03-15 | 2016-12-15 | The Trustees Of The University Of Pennsylvania | Mono or multivalent botulinum neurotoxin based vaccine using the heavy chain from serotypes of Clostridium botulinum |
| WO2015132004A1 (en) | 2014-03-05 | 2015-09-11 | Merz Pharma Gmbh & Co. Kgaa | Novel recombinant clostridial neurotoxins with increased duration of effect |
| US11897921B2 (en) | 2014-12-09 | 2024-02-13 | New York University | Propeptide fusion comprising a mutated clostridium botulinum neurotoxin and a VHH domain |
| KR102514666B1 (ko) | 2014-12-19 | 2023-03-27 | 메르츠 파마 게엠베하 운트 코. 카가아 | 세포에서 BoNT/E의 생물학적 활성의 결정을 위한 수단 및 방법 |
| WO2016110662A1 (en) * | 2015-01-09 | 2016-07-14 | Ipsen Bioinnovation Limited | Cationic neurotoxins |
| TW201718627A (zh) | 2015-06-11 | 2017-06-01 | 梅茲製藥有限兩合公司 | 重組梭菌神經毒素及其使用與形成方法、包括其之醫藥組合物及對應其之前驅物、編碼前驅物之核酸序列及其獲得方法與前驅物之形成方法、載體與包括核酸序列之重組宿主細胞 |
| US11078472B2 (en) | 2016-01-20 | 2021-08-03 | Merz Pharma Gmbh & Co., Kgaa | Recombinant clostridial neurotoxins with increased duration of effect |
| CN108463242A (zh) | 2016-03-02 | 2018-08-28 | 梅尔兹制药公司 | 包含肉毒杆菌毒素的组合物 |
| EP3290437A1 (en) | 2016-08-31 | 2018-03-07 | Merz Pharma GmbH & Co. KGaA | Novel recombinant clostridial neurotoxins with decreased duration of effect |
| KR102480965B1 (ko) | 2016-09-13 | 2022-12-26 | 알레간 인코포레이티드 | 안정화된 비단백질 클로스트리듐 독소 조성물 |
| EP3312193A1 (en) | 2016-10-19 | 2018-04-25 | Merz Pharma GmbH & Co. KGaA | Novel recombinant botulinum neurotoxins with accelerated onset of effect |
| EP3333179A1 (en) | 2016-12-07 | 2018-06-13 | Merz Pharma GmbH & Co. KGaA | Novel recombinant botulinum toxin with accelarated onset of effect |
| EP3335719A1 (en) | 2016-12-14 | 2018-06-20 | Merz Pharma GmbH & Co. KGaA | Novel recombinant botulinum neurotoxins with a stabilized light chain |
| WO2018233813A1 (en) | 2017-06-20 | 2018-12-27 | Merz Pharma Gmbh & Co. Kgaa | NOVEL RECOMBINANT BOTULINUM TOXINS WITH INCREASED DURATION |
| EP3649143B1 (en) | 2017-07-06 | 2022-08-31 | Merz Pharma GmbH & Co. KGaA | Novel recombinant botulinum neurotoxins with increased duration of effect |
| US20210008156A1 (en) | 2017-10-26 | 2021-01-14 | Merz Pharma Gmbh & Co. Kgaa | Novel recombinant botulinum neurotoxins with increased duration of effect |
| US20200354706A1 (en) | 2017-11-22 | 2020-11-12 | Merz Pharma Gmbh & Co. Kgaa | Novel recombinant botulinum toxin with increased duration of effect |
| WO2019152380A1 (en) * | 2018-01-30 | 2019-08-08 | Children's Medical Center Corporation | Production of botulinum neurotoxins using bacillus systems |
| US11707510B2 (en) * | 2018-02-16 | 2023-07-25 | Preclinics Discovery Gmbh | Nucleic acid-based botulinum neurotoxin for therapeutic use |
| EP3931319A1 (en) * | 2019-02-28 | 2022-01-05 | ProteoNic Biotechnology IP B.V. | Self-immolative plasmid backbone |
| US20240158773A1 (en) * | 2021-03-15 | 2024-05-16 | Children's Medical Center Cprporation | Engineered botulinum neurotoxin a protease domain with improved efficacy |
| GB202104294D0 (en) * | 2021-03-26 | 2021-05-12 | Ipsen Biopharm Ltd | Clostridial neurotoxins comprising an exogenous activation loop |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2003383A1 (en) * | 1988-11-23 | 1990-05-23 | Sushil G. Devare | Synthetic dna derived recombinant hiv antigens |
| UA48104C2 (uk) * | 1991-10-04 | 2002-08-15 | Новартіс Аг | Фрагмент днк, який містить послідовність,що кодує інсектицидний протеїн, оптимізовану для кукурудзи,фрагмент днк, який забезпечує направлену бажану для серцевини стебла експресію зв'язаного з нею структурного гена в рослині, фрагмент днк, який забезпечує специфічну для пилку експресію зв`язаного з нею структурного гена в рослині, рекомбінантна молекула днк, спосіб одержання оптимізованої для кукурудзи кодуючої послідовності інсектицидного протеїну, спосіб захисту рослин кукурудзи щонайменше від однієї комахи-шкідника |
| US7214787B1 (en) * | 1993-09-21 | 2007-05-08 | United States Of America As Represented By The Secretary Of The Army | Recombinant vaccine against botulinum neurotoxin |
| US7037680B2 (en) * | 1993-09-21 | 2006-05-02 | The United States Of America As Represented By The Secretary Of The Army | Recombinant light chains of botulinum neurotoxins and light chain fusion proteins for use in research and clinical therapy |
| NZ295998A (en) * | 1994-10-24 | 1999-10-28 | Ophidian Pharm Inc | Neutralizing antitoxins against clostridium difficile and clostidium botulinum toxins |
| US6114148C1 (en) * | 1996-09-20 | 2012-05-01 | Gen Hospital Corp | High level expression of proteins |
| US6392022B1 (en) * | 1997-07-11 | 2002-05-21 | Chugai Seiyaku Kabushiki Kaisha | Gene originating in human chondrocyte |
| US6277622B1 (en) * | 1997-08-11 | 2001-08-21 | The University Of Sydney | Synthetic polynucleotides |
| US6218188B1 (en) * | 1997-11-12 | 2001-04-17 | Mycogen Corporation | Plant-optimized genes encoding pesticidal toxins |
| US6214602B1 (en) * | 1998-08-28 | 2001-04-10 | Promega Corporation | Host cells for expression of clostridial toxins and proteins |
| AU783450B2 (en) * | 1999-05-12 | 2005-10-27 | United States Army Medical Research Materiel Command (Usamrmc) | Recombinant vaccine against botulinum neurotoxin |
| US6399857B1 (en) * | 1999-09-22 | 2002-06-04 | Paradigm Genetics, Inc. | Modified nucleotide sequence encoding a LexA DNA binding domain optimized for arabidopsis species |
| AU2002211490A1 (en) * | 2000-10-04 | 2002-04-15 | The Trustees Of The University Of Pennsylvania | Compositions and methods of using capsid protein from flaviviruses and pestiviruses |
| AU2003249208B2 (en) * | 2002-07-16 | 2010-03-04 | Vgx Pharmaceuticals, Llc | Codon optimized synthetic plasmids |
| US20080057575A1 (en) * | 2004-08-04 | 2008-03-06 | Allergan, Inc. | Optimizing Expression of Active Botulinum Toxin Type A |
-
2005
- 2005-08-03 US US11/570,706 patent/US20080057575A1/en not_active Abandoned
- 2005-08-03 WO PCT/US2005/027917 patent/WO2006017749A2/en not_active Ceased
- 2005-08-03 AU AU2005271372A patent/AU2005271372B2/en not_active Ceased
- 2005-08-03 CA CA002575994A patent/CA2575994A1/en not_active Abandoned
- 2005-08-03 JP JP2007525034A patent/JP2008508886A/ja active Pending
- 2005-08-03 EP EP05778839A patent/EP1773874B1/en not_active Revoked
-
2008
- 2008-08-15 US US12/192,873 patent/US20090023198A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20090023198A1 (en) | 2009-01-22 |
| JP2008508886A (ja) | 2008-03-27 |
| WO2006017749A3 (en) | 2006-03-30 |
| AU2005271372A1 (en) | 2006-02-16 |
| EP1773874B1 (en) | 2012-10-24 |
| US20080057575A1 (en) | 2008-03-06 |
| AU2005271372B2 (en) | 2012-05-03 |
| EP1773874A2 (en) | 2007-04-18 |
| WO2006017749A2 (en) | 2006-02-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2005271372B2 (en) | Optimizing expression of active botulinum toxin type A | |
| US7825233B2 (en) | Optimizing expression of active Botulinum Toxin type E | |
| EP2178905B1 (en) | Methods of activiting clostridial toxins | |
| EP2154151B1 (en) | Clostridial toxin activatable clostridial toxins | |
| EP2505592A1 (en) | Modified clostridial toxins with enhanced translocation capability and enhanced targeting activity | |
| EP1784420A1 (en) | Degradable clostridial toxins | |
| CA2657521A1 (en) | Modified clostridial toxins with enhanced translocation capabilities and altered targeting activity for non-clostridial toxin target cells | |
| CA2784666A1 (en) | Modified clostridial toxins comprising an integrated protease cleavage site-binding domain | |
| US20110111483A1 (en) | Optimizing Expression of Active Botulinum Toxin Type E | |
| US20130288336A1 (en) | Methods of activating clostridial toxins | |
| AU2012211346A1 (en) | Optimizing expression of active botulinum toxin type A | |
| AU2013204638A1 (en) | Optimizing expression of active botulinum toxin type A | |
| AU2012201413A1 (en) | Clostridial toxin activatable clostridial toxins |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Dead |
Effective date: 20151027 |