CA2992511A1 - Systemic synthesis and regulation of l-dopa - Google Patents
Systemic synthesis and regulation of l-dopa Download PDFInfo
- Publication number
- CA2992511A1 CA2992511A1 CA2992511A CA2992511A CA2992511A1 CA 2992511 A1 CA2992511 A1 CA 2992511A1 CA 2992511 A CA2992511 A CA 2992511A CA 2992511 A CA2992511 A CA 2992511A CA 2992511 A1 CA2992511 A1 CA 2992511A1
- Authority
- CA
- Canada
- Prior art keywords
- seq
- expression system
- group
- polypeptide
- promoter
- 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
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 title claims abstract description 127
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 title claims abstract description 125
- 230000015572 biosynthetic process Effects 0.000 title description 22
- 238000003786 synthesis reaction Methods 0.000 title description 13
- 230000033228 biological regulation Effects 0.000 title description 8
- 230000009885 systemic effect Effects 0.000 title description 8
- 230000014509 gene expression Effects 0.000 claims abstract description 477
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims abstract description 102
- 229960003638 dopamine Drugs 0.000 claims abstract description 52
- 208000018737 Parkinson disease Diseases 0.000 claims abstract description 44
- 238000011282 treatment Methods 0.000 claims abstract description 43
- 150000003943 catecholamines Chemical class 0.000 claims abstract description 39
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 39
- 210000004369 blood Anatomy 0.000 claims abstract description 26
- 239000008280 blood Substances 0.000 claims abstract description 26
- 238000007910 systemic administration Methods 0.000 claims abstract description 6
- 108091000117 Tyrosine 3-Monooxygenase Proteins 0.000 claims description 273
- 102000048218 Tyrosine 3-monooxygenases Human genes 0.000 claims description 266
- 102100027346 GTP cyclohydrolase 1 Human genes 0.000 claims description 210
- 229920001184 polypeptide Polymers 0.000 claims description 195
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 195
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 195
- 108091033319 polynucleotide Proteins 0.000 claims description 174
- 102000040430 polynucleotide Human genes 0.000 claims description 174
- 239000002157 polynucleotide Substances 0.000 claims description 174
- 101710094136 GTP cyclohydrolase 1 Proteins 0.000 claims description 168
- 239000013598 vector Substances 0.000 claims description 153
- 239000012634 fragment Substances 0.000 claims description 134
- 108010045523 6-pyruvoyltetrahydropterin synthase Proteins 0.000 claims description 123
- 102100028505 6-pyruvoyl tetrahydrobiopterin synthase Human genes 0.000 claims description 122
- 210000004027 cell Anatomy 0.000 claims description 89
- 238000000034 method Methods 0.000 claims description 67
- 150000001413 amino acids Chemical class 0.000 claims description 62
- 210000004185 liver Anatomy 0.000 claims description 62
- 241000282414 Homo sapiens Species 0.000 claims description 54
- 102000004190 Enzymes Human genes 0.000 claims description 52
- 108090000790 Enzymes Proteins 0.000 claims description 52
- 239000008194 pharmaceutical composition Substances 0.000 claims description 49
- 239000002773 nucleotide Substances 0.000 claims description 43
- 125000003729 nucleotide group Chemical group 0.000 claims description 43
- 108090000623 proteins and genes Proteins 0.000 claims description 43
- 239000013612 plasmid Substances 0.000 claims description 42
- 210000000234 capsid Anatomy 0.000 claims description 38
- 230000002093 peripheral effect Effects 0.000 claims description 31
- 230000001105 regulatory effect Effects 0.000 claims description 31
- FNKQXYHWGSIFBK-RPDRRWSUSA-N sapropterin Chemical compound N1=C(N)NC(=O)C2=C1NC[C@H]([C@@H](O)[C@@H](O)C)N2 FNKQXYHWGSIFBK-RPDRRWSUSA-N 0.000 claims description 31
- 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 claims description 29
- 210000003205 muscle Anatomy 0.000 claims description 28
- 241000702423 Adeno-associated virus - 2 Species 0.000 claims description 27
- 201000010099 disease Diseases 0.000 claims description 26
- 230000002255 enzymatic effect Effects 0.000 claims description 25
- 208000012661 Dyskinesia Diseases 0.000 claims description 24
- 230000004064 dysfunction Effects 0.000 claims description 22
- 230000001225 therapeutic effect Effects 0.000 claims description 22
- 230000000694 effects Effects 0.000 claims description 19
- 241001634120 Adeno-associated virus - 5 Species 0.000 claims description 18
- 210000003169 central nervous system Anatomy 0.000 claims description 18
- 239000003623 enhancer Substances 0.000 claims description 18
- 239000013603 viral vector Substances 0.000 claims description 18
- 241001164825 Adeno-associated virus - 8 Species 0.000 claims description 17
- 210000004962 mammalian cell Anatomy 0.000 claims description 17
- 241001655883 Adeno-associated virus - 1 Species 0.000 claims description 16
- 241000972680 Adeno-associated virus - 6 Species 0.000 claims description 16
- 241001164823 Adeno-associated virus - 7 Species 0.000 claims description 16
- 108020004414 DNA Proteins 0.000 claims description 16
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 claims description 16
- 241001492404 Woodchuck hepatitis virus Species 0.000 claims description 16
- 230000004071 biological effect Effects 0.000 claims description 16
- 239000003954 decarboxylase inhibitor Substances 0.000 claims description 16
- 102000004169 proteins and genes Human genes 0.000 claims description 16
- 108010023555 GTP Cyclohydrolase Proteins 0.000 claims description 15
- 210000000663 muscle cell Anatomy 0.000 claims description 15
- 230000001124 posttranscriptional effect Effects 0.000 claims description 15
- 102000006378 Catechol O-methyltransferase Human genes 0.000 claims description 14
- 108020002739 Catechol O-methyltransferase Proteins 0.000 claims description 14
- 102000036509 GTP Cyclohydrolase Human genes 0.000 claims description 14
- 150000007523 nucleic acids Chemical group 0.000 claims description 14
- 229960004617 sapropterin Drugs 0.000 claims description 14
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 13
- 238000001990 intravenous administration Methods 0.000 claims description 13
- 230000008488 polyadenylation Effects 0.000 claims description 13
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 claims description 12
- 230000007812 deficiency Effects 0.000 claims description 11
- 208000035475 disorder Diseases 0.000 claims description 11
- 210000003494 hepatocyte Anatomy 0.000 claims description 11
- 102000010292 Peptide Elongation Factor 1 Human genes 0.000 claims description 10
- 108010077524 Peptide Elongation Factor 1 Proteins 0.000 claims description 10
- 230000003197 catalytic effect Effects 0.000 claims description 10
- 239000003795 chemical substances by application Substances 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- 239000003112 inhibitor Substances 0.000 claims description 10
- 239000013607 AAV vector Substances 0.000 claims description 9
- 125000000539 amino acid group Chemical group 0.000 claims description 9
- 239000003543 catechol methyltransferase inhibitor Substances 0.000 claims description 9
- 210000003098 myoblast Anatomy 0.000 claims description 9
- 210000000107 myocyte Anatomy 0.000 claims description 9
- 210000003462 vein Anatomy 0.000 claims description 9
- 101000862581 Homo sapiens GTP cyclohydrolase 1 Proteins 0.000 claims description 7
- 229940079593 drug Drugs 0.000 claims description 7
- 229960003337 entacapone Drugs 0.000 claims description 7
- JRURYQJSLYLRLN-BJMVGYQFSA-N entacapone Chemical compound CCN(CC)C(=O)C(\C#N)=C\C1=CC(O)=C(O)C([N+]([O-])=O)=C1 JRURYQJSLYLRLN-BJMVGYQFSA-N 0.000 claims description 7
- 108020004999 messenger RNA Proteins 0.000 claims description 7
- 239000002243 precursor Substances 0.000 claims description 7
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 claims description 6
- 108010065729 Troponin I Proteins 0.000 claims description 6
- 230000001684 chronic effect Effects 0.000 claims description 6
- 210000005229 liver cell Anatomy 0.000 claims description 6
- 230000010412 perfusion Effects 0.000 claims description 6
- 102000004420 Creatine Kinase Human genes 0.000 claims description 5
- 108010042126 Creatine kinase Proteins 0.000 claims description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 5
- 230000005856 abnormality Effects 0.000 claims description 5
- 230000006378 damage Effects 0.000 claims description 5
- 230000001939 inductive effect Effects 0.000 claims description 5
- 238000007918 intramuscular administration Methods 0.000 claims description 5
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 5
- 238000004806 packaging method and process Methods 0.000 claims description 5
- 210000003240 portal vein Anatomy 0.000 claims description 5
- 208000033996 Autosomal recessive dopa-responsive dystonia Diseases 0.000 claims description 4
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 claims description 4
- 229960004603 tolcapone Drugs 0.000 claims description 4
- MIQPIUSUKVNLNT-UHFFFAOYSA-N tolcapone Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC(O)=C(O)C([N+]([O-])=O)=C1 MIQPIUSUKVNLNT-UHFFFAOYSA-N 0.000 claims description 4
- 230000002463 transducing effect Effects 0.000 claims description 4
- 208000015573 tyrosine hydroxylase deficiency Diseases 0.000 claims description 4
- 102000007469 Actins Human genes 0.000 claims description 3
- 108010085238 Actins Proteins 0.000 claims description 3
- 208000015798 BH4-deficient hyperphenylalaninemia B Diseases 0.000 claims description 3
- 208000002603 Dopa-responsive dystonia Diseases 0.000 claims description 3
- 102000015554 Dopamine receptor Human genes 0.000 claims description 3
- 108050004812 Dopamine receptor Proteins 0.000 claims description 3
- 210000004507 artificial chromosome Anatomy 0.000 claims description 3
- 229960004205 carbidopa Drugs 0.000 claims description 3
- TZFNLOMSOLWIDK-JTQLQIEISA-N carbidopa (anhydrous) Chemical compound NN[C@@](C(O)=O)(C)CC1=CC=C(O)C(O)=C1 TZFNLOMSOLWIDK-JTQLQIEISA-N 0.000 claims description 3
- 238000007911 parenteral administration Methods 0.000 claims description 3
- 210000001428 peripheral nervous system Anatomy 0.000 claims description 3
- 229960003387 progesterone Drugs 0.000 claims description 3
- 239000000186 progesterone Substances 0.000 claims description 3
- 230000001177 retroviral effect Effects 0.000 claims description 3
- 238000007920 subcutaneous administration Methods 0.000 claims description 3
- 230000002792 vascular Effects 0.000 claims description 3
- 206010001367 Adrenal insufficiency Diseases 0.000 claims description 2
- 102000003823 Aromatic-L-amino-acid decarboxylases Human genes 0.000 claims description 2
- 108090000121 Aromatic-L-amino-acid decarboxylases Proteins 0.000 claims description 2
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 2
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 2
- 206010012289 Dementia Diseases 0.000 claims description 2
- 208000001613 Gambling Diseases 0.000 claims description 2
- 206010020772 Hypertension Diseases 0.000 claims description 2
- 208000001953 Hypotension Diseases 0.000 claims description 2
- 208000009829 Lewy Body Disease Diseases 0.000 claims description 2
- 201000002832 Lewy body dementia Diseases 0.000 claims description 2
- 208000005565 Marijuana Use Diseases 0.000 claims description 2
- 208000001089 Multiple system atrophy Diseases 0.000 claims description 2
- UPMRZALMHVUCIN-UHFFFAOYSA-N Nitecapone Chemical compound CC(=O)C(C(C)=O)=CC1=CC(O)=C(O)C([N+]([O-])=O)=C1 UPMRZALMHVUCIN-UHFFFAOYSA-N 0.000 claims description 2
- 206010034158 Pathological gambling Diseases 0.000 claims description 2
- 241000288906 Primates Species 0.000 claims description 2
- 206010068100 Vascular parkinsonism Diseases 0.000 claims description 2
- 208000017515 adrenocortical insufficiency Diseases 0.000 claims description 2
- 210000004227 basal ganglia Anatomy 0.000 claims description 2
- 230000037326 chronic stress Effects 0.000 claims description 2
- 229960003920 cocaine Drugs 0.000 claims description 2
- 239000013601 cosmid vector Substances 0.000 claims description 2
- 108700006189 dopamine beta hydroxylase deficiency Proteins 0.000 claims description 2
- 208000009308 dopamine beta-hydroxylase deficiency Diseases 0.000 claims description 2
- 230000000632 dystonic effect Effects 0.000 claims description 2
- 201000006517 essential tremor Diseases 0.000 claims description 2
- 210000003527 eukaryotic cell Anatomy 0.000 claims description 2
- 230000002068 genetic effect Effects 0.000 claims description 2
- 210000005260 human cell Anatomy 0.000 claims description 2
- 230000036543 hypotension Effects 0.000 claims description 2
- 229950008980 nitecapone Drugs 0.000 claims description 2
- 208000028173 post-traumatic stress disease Diseases 0.000 claims description 2
- 201000002212 progressive supranuclear palsy Diseases 0.000 claims description 2
- 238000011321 prophylaxis Methods 0.000 claims description 2
- 201000000980 schizophrenia Diseases 0.000 claims description 2
- 230000001502 supplementing effect Effects 0.000 claims description 2
- 102000009659 Vesicular Monoamine Transport Proteins Human genes 0.000 claims 3
- 108010020033 Vesicular Monoamine Transport Proteins Proteins 0.000 claims 3
- 101100228519 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) gch-1 gene Proteins 0.000 claims 2
- 108010078791 Carrier Proteins Proteins 0.000 claims 1
- 102000014914 Carrier Proteins Human genes 0.000 claims 1
- 102000034287 fluorescent proteins Human genes 0.000 claims 1
- 108091006047 fluorescent proteins Proteins 0.000 claims 1
- 230000002950 deficient Effects 0.000 abstract description 3
- 238000002641 enzyme replacement therapy Methods 0.000 abstract description 2
- 229940024606 amino acid Drugs 0.000 description 62
- 235000001014 amino acid Nutrition 0.000 description 62
- 241001465754 Metazoa Species 0.000 description 30
- 238000004519 manufacturing process Methods 0.000 description 30
- 241000699670 Mus sp. Species 0.000 description 25
- 210000001519 tissue Anatomy 0.000 description 17
- 238000011144 upstream manufacturing Methods 0.000 description 16
- 241000699666 Mus <mouse, genus> Species 0.000 description 15
- 238000002347 injection Methods 0.000 description 15
- 239000007924 injection Substances 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 13
- 230000035772 mutation Effects 0.000 description 13
- 238000010361 transduction Methods 0.000 description 13
- 230000026683 transduction Effects 0.000 description 13
- 229960004441 tyrosine Drugs 0.000 description 13
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 12
- 238000001415 gene therapy Methods 0.000 description 12
- 239000000203 mixture Substances 0.000 description 12
- 230000026731 phosphorylation Effects 0.000 description 12
- 238000006366 phosphorylation reaction Methods 0.000 description 12
- 235000018102 proteins Nutrition 0.000 description 12
- 230000028327 secretion Effects 0.000 description 11
- 238000002560 therapeutic procedure Methods 0.000 description 11
- 239000004698 Polyethylene Substances 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 9
- 229960004502 levodopa Drugs 0.000 description 9
- MHUWZNTUIIFHAS-CLFAGFIQSA-N dioleoyl phosphatidic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(COP(O)(O)=O)OC(=O)CCCCCCC\C=C/CCCCCCCC MHUWZNTUIIFHAS-CLFAGFIQSA-N 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- 230000004044 response Effects 0.000 description 8
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 8
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 8
- 208000014094 Dystonic disease Diseases 0.000 description 7
- 102100039089 Tyrosine 3-monooxygenase Human genes 0.000 description 7
- 125000003275 alpha amino acid group Chemical group 0.000 description 7
- 210000004556 brain Anatomy 0.000 description 7
- 238000010367 cloning Methods 0.000 description 7
- 239000003136 dopamine receptor stimulating agent Substances 0.000 description 7
- 208000010118 dystonia Diseases 0.000 description 7
- 239000013604 expression vector Substances 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- 238000001802 infusion Methods 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 238000013518 transcription Methods 0.000 description 7
- 230000035897 transcription Effects 0.000 description 7
- 230000014616 translation Effects 0.000 description 7
- 102000053602 DNA Human genes 0.000 description 6
- 241000702421 Dependoparvovirus Species 0.000 description 6
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 6
- 102100021244 Integral membrane protein GPR180 Human genes 0.000 description 6
- 108010029485 Protein Isoforms Proteins 0.000 description 6
- 102000001708 Protein Isoforms Human genes 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- 241000700605 Viruses Species 0.000 description 6
- 230000001154 acute effect Effects 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 201000003323 dystonia 5 Diseases 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000013646 rAAV2 vector Substances 0.000 description 6
- 230000008685 targeting Effects 0.000 description 6
- 229940123736 Decarboxylase inhibitor Drugs 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 238000010276 construction Methods 0.000 description 5
- 210000005064 dopaminergic neuron Anatomy 0.000 description 5
- 230000003836 peripheral circulation Effects 0.000 description 5
- 210000002948 striated muscle cell Anatomy 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 238000013519 translation Methods 0.000 description 5
- WTDRDQBEARUVNC-HXQNXAKUSA-N (2S)-3-deuterio-2-(dideuterioamino)-3-(3,4-dihydroxyphenyl)propanoic acid Chemical compound O=C(O)[C@@H](N([2H])[2H])C(C1=CC=C(O)C(O)=C1)[2H] WTDRDQBEARUVNC-HXQNXAKUSA-N 0.000 description 4
- 102000000632 Aromatic amino acid hydroxylases Human genes 0.000 description 4
- 108050008079 Aromatic amino acid hydroxylases Proteins 0.000 description 4
- 102000008109 Mixed Function Oxygenases Human genes 0.000 description 4
- 108010074633 Mixed Function Oxygenases Proteins 0.000 description 4
- 238000012408 PCR amplification Methods 0.000 description 4
- 108010069013 Phenylalanine Hydroxylase Proteins 0.000 description 4
- 102100038223 Phenylalanine-4-hydroxylase Human genes 0.000 description 4
- 102000001253 Protein Kinase Human genes 0.000 description 4
- 101150076211 TH gene Proteins 0.000 description 4
- 108010031944 Tryptophan Hydroxylase Proteins 0.000 description 4
- 102000005506 Tryptophan Hydroxylase Human genes 0.000 description 4
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
- 230000002411 adverse Effects 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- BNQDCRGUHNALGH-UHFFFAOYSA-N benserazide Chemical compound OCC(N)C(=O)NNCC1=CC=C(O)C(O)=C1O BNQDCRGUHNALGH-UHFFFAOYSA-N 0.000 description 4
- 229960000911 benserazide Drugs 0.000 description 4
- 230000008499 blood brain barrier function Effects 0.000 description 4
- 210000001218 blood-brain barrier Anatomy 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 238000011284 combination treatment Methods 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- WBJZXBUVECZHCE-UHFFFAOYSA-N dyspropterin Chemical compound N1=C(N)NC(=O)C2=C1NCC(C(=O)C(=O)C)N2 WBJZXBUVECZHCE-UHFFFAOYSA-N 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 210000001035 gastrointestinal tract Anatomy 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 230000001965 increasing effect Effects 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 210000001577 neostriatum Anatomy 0.000 description 4
- 239000002858 neurotransmitter agent Substances 0.000 description 4
- 230000007935 neutral effect Effects 0.000 description 4
- 102000039446 nucleic acids Human genes 0.000 description 4
- 108020004707 nucleic acids Proteins 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 4
- 108060006633 protein kinase Proteins 0.000 description 4
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000001890 transfection Methods 0.000 description 4
- 238000012546 transfer Methods 0.000 description 4
- 238000011269 treatment regimen Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 101000606113 Homo sapiens Tyrosine 3-monooxygenase Proteins 0.000 description 3
- 241000713666 Lentivirus Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 241000283984 Rodentia Species 0.000 description 3
- 210000002934 adrenergic neuron Anatomy 0.000 description 3
- 238000012761 co-transfection Methods 0.000 description 3
- 230000000295 complement effect Effects 0.000 description 3
- 230000007547 defect Effects 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- 230000029087 digestion Effects 0.000 description 3
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 3
- 229940052760 dopamine agonists Drugs 0.000 description 3
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 3
- 210000003414 extremity Anatomy 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 230000002440 hepatic effect Effects 0.000 description 3
- 230000006801 homologous recombination Effects 0.000 description 3
- 238000002744 homologous recombination Methods 0.000 description 3
- 230000033444 hydroxylation Effects 0.000 description 3
- 238000005805 hydroxylation reaction Methods 0.000 description 3
- 238000007912 intraperitoneal administration Methods 0.000 description 3
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 230000036470 plasma concentration Effects 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 238000001243 protein synthesis Methods 0.000 description 3
- 238000003908 quality control method Methods 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 238000012163 sequencing technique Methods 0.000 description 3
- 235000004400 serine Nutrition 0.000 description 3
- 230000037432 silent mutation Effects 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 230000002459 sustained effect Effects 0.000 description 3
- 230000002103 transcriptional effect Effects 0.000 description 3
- 230000014621 translational initiation Effects 0.000 description 3
- 101150064818 tth gene Proteins 0.000 description 3
- 241001430294 unidentified retrovirus Species 0.000 description 3
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 2
- VIYKYVYAKVNDPS-HKGPVOKGSA-N (2s)-2-azanyl-3-[3,4-bis(oxidanyl)phenyl]propanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1.OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 VIYKYVYAKVNDPS-HKGPVOKGSA-N 0.000 description 2
- DGGUVLXVLHAAGT-XINAWCOVSA-N 7,8-dihydroneopterin 3'-triphosphate Chemical compound N1CC([C@H](O)[C@H](O)COP(O)(=O)OP(O)(=O)OP(O)(O)=O)=NC2=C1N=C(N)NC2=O DGGUVLXVLHAAGT-XINAWCOVSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 244000180534 Berberis hybrid Species 0.000 description 2
- 102100026735 Coagulation factor VIII Human genes 0.000 description 2
- 208000028698 Cognitive impairment Diseases 0.000 description 2
- LHQIJBMDNUYRAM-AWFVSMACSA-N D-erythro-biopterin Chemical compound N1=C(N)NC(=O)C2=NC([C@H](O)[C@H](O)C)=CN=C21 LHQIJBMDNUYRAM-AWFVSMACSA-N 0.000 description 2
- 230000006820 DNA synthesis Effects 0.000 description 2
- 101150004665 GCH1 gene Proteins 0.000 description 2
- 102300049212 GTP cyclohydrolase 1 isoform GCH-3 Human genes 0.000 description 2
- 102300049247 GTP cyclohydrolase 1 isoform GCH-4 Human genes 0.000 description 2
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical group [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- LHQIJBMDNUYRAM-UHFFFAOYSA-N L-erythro-Biopterin Natural products N1=C(N)NC(=O)C2=NC(C(O)C(O)C)=CN=C21 LHQIJBMDNUYRAM-UHFFFAOYSA-N 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- 238000011887 Necropsy Methods 0.000 description 2
- 208000012902 Nervous system disease Diseases 0.000 description 2
- 208000025966 Neurological disease Diseases 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 208000027089 Parkinsonian disease Diseases 0.000 description 2
- 206010034010 Parkinsonism Diseases 0.000 description 2
- 108091093037 Peptide nucleic acid Proteins 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 201000011252 Phenylketonuria Diseases 0.000 description 2
- 241000700157 Rattus norvegicus Species 0.000 description 2
- 108091081062 Repeated sequence (DNA) Proteins 0.000 description 2
- 208000005793 Restless legs syndrome Diseases 0.000 description 2
- 108020004682 Single-Stranded DNA Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000004098 Tetracycline Substances 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- UCTWMZQNUQWSLP-UHFFFAOYSA-N adrenaline Chemical compound CNCC(O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-UHFFFAOYSA-N 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 229940121375 antifungal agent Drugs 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 238000004820 blood count Methods 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 239000013611 chromosomal DNA Substances 0.000 description 2
- 208000010877 cognitive disease Diseases 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000006114 decarboxylation reaction Methods 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 208000037765 diseases and disorders Diseases 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 239000002612 dispersion medium Substances 0.000 description 2
- -1 dopamine Chemical class 0.000 description 2
- 230000002183 duodenal effect Effects 0.000 description 2
- 239000003792 electrolyte Substances 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 235000012631 food intake Nutrition 0.000 description 2
- 108020001507 fusion proteins Proteins 0.000 description 2
- 102000037865 fusion proteins Human genes 0.000 description 2
- 238000001502 gel electrophoresis Methods 0.000 description 2
- 238000003364 immunohistochemistry Methods 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- 239000007951 isotonicity adjuster Substances 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 238000007449 liver function test Methods 0.000 description 2
- 210000005228 liver tissue Anatomy 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 210000003141 lower extremity Anatomy 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 229960002748 norepinephrine Drugs 0.000 description 2
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- DIVDFFZHCJEHGG-UHFFFAOYSA-N oxidopamine Chemical compound NCCC1=CC(O)=C(O)C=C1O DIVDFFZHCJEHGG-UHFFFAOYSA-N 0.000 description 2
- 230000001144 postural effect Effects 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 238000003259 recombinant expression Methods 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 229940076279 serotonin Drugs 0.000 description 2
- 210000002027 skeletal muscle Anatomy 0.000 description 2
- 210000002460 smooth muscle Anatomy 0.000 description 2
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 2
- 235000010262 sodium metabisulphite Nutrition 0.000 description 2
- 239000004296 sodium metabisulphite Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 210000003699 striated muscle Anatomy 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- 230000009469 supplementation Effects 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 229960002180 tetracycline Drugs 0.000 description 2
- 229930101283 tetracycline Natural products 0.000 description 2
- 235000019364 tetracycline Nutrition 0.000 description 2
- 150000003522 tetracyclines Chemical class 0.000 description 2
- 230000000451 tissue damage Effects 0.000 description 2
- 231100000827 tissue damage Toxicity 0.000 description 2
- 239000001226 triphosphate Substances 0.000 description 2
- 235000011178 triphosphate Nutrition 0.000 description 2
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 2
- 241000701161 unidentified adenovirus Species 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- IVTMXOXVAHXCHI-YXLMWLKOSA-N (2s)-2-amino-3-(3,4-dihydroxyphenyl)propanoic acid;(2s)-3-(3,4-dihydroxyphenyl)-2-hydrazinyl-2-methylpropanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1.NN[C@@](C(O)=O)(C)CC1=CC=C(O)C(O)=C1 IVTMXOXVAHXCHI-YXLMWLKOSA-N 0.000 description 1
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
- 229930182837 (R)-adrenaline Natural products 0.000 description 1
- VUFNLQXQSDUXKB-DOFZRALJSA-N 2-[4-[4-[bis(2-chloroethyl)amino]phenyl]butanoyloxy]ethyl (5z,8z,11z,14z)-icosa-5,8,11,14-tetraenoate Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)OCCOC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 VUFNLQXQSDUXKB-DOFZRALJSA-N 0.000 description 1
- CFFZDZCDUFSOFZ-UHFFFAOYSA-N 3,4-Dihydroxy-phenylacetic acid Chemical compound OC(=O)CC1=CC=C(O)C(O)=C1 CFFZDZCDUFSOFZ-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 241000710929 Alphavirus Species 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 244000144725 Amygdalus communis Species 0.000 description 1
- 208000033388 Autosomal dominant dopa-responsive dystonia Diseases 0.000 description 1
- 241000701822 Bovine papillomavirus Species 0.000 description 1
- 102000004657 Calcium-Calmodulin-Dependent Protein Kinase Type 2 Human genes 0.000 description 1
- 108010003721 Calcium-Calmodulin-Dependent Protein Kinase Type 2 Proteins 0.000 description 1
- 206010007269 Carcinogenicity Diseases 0.000 description 1
- 102100022641 Coagulation factor IX Human genes 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 108091033380 Coding strand Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 241001573498 Compacta Species 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 241000711573 Coronaviridae Species 0.000 description 1
- 102000008130 Cyclic AMP-Dependent Protein Kinases Human genes 0.000 description 1
- 108010049894 Cyclic AMP-Dependent Protein Kinases Proteins 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 241000713730 Equine infectious anemia virus Species 0.000 description 1
- 108010076282 Factor IX Proteins 0.000 description 1
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 1
- 241000713800 Feline immunodeficiency virus Species 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 102300049213 GTP cyclohydrolase 1 isoform GCH-2 Human genes 0.000 description 1
- 208000011370 GTP cyclohydrolase I deficiency Diseases 0.000 description 1
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
- 206010018341 Gliosis Diseases 0.000 description 1
- 102100036263 Glutamyl-tRNA(Gln) amidotransferase subunit C, mitochondrial Human genes 0.000 description 1
- 206010019375 Helicobacter infections Diseases 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101001001786 Homo sapiens Glutamyl-tRNA(Gln) amidotransferase subunit C, mitochondrial Proteins 0.000 description 1
- 101100101249 Homo sapiens TH gene Proteins 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 102000004157 Hydrolases Human genes 0.000 description 1
- 108090000604 Hydrolases Proteins 0.000 description 1
- 208000021199 Hyperphenylalaninemia due to tetrahydrobiopterin deficiency Diseases 0.000 description 1
- 206010020843 Hyperthermia Diseases 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- 208000032382 Ischaemic stroke Diseases 0.000 description 1
- 108010044467 Isoenzymes Proteins 0.000 description 1
- 108010059343 MM Form Creatine Kinase Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- YJPIGAIKUZMOQA-UHFFFAOYSA-N Melatonin Natural products COC1=CC=C2N(C(C)=O)C=C(CCN)C2=C1 YJPIGAIKUZMOQA-UHFFFAOYSA-N 0.000 description 1
- 208000036626 Mental retardation Diseases 0.000 description 1
- 108010006519 Molecular Chaperones Proteins 0.000 description 1
- 102000005431 Molecular Chaperones Human genes 0.000 description 1
- 241000713869 Moloney murine leukemia virus Species 0.000 description 1
- 208000019022 Mood disease Diseases 0.000 description 1
- 206010067482 No adverse event Diseases 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 229920002732 Polyanhydride Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- 229920002685 Polyoxyl 35CastorOil Polymers 0.000 description 1
- 206010037213 Psychomotor retardation Diseases 0.000 description 1
- 238000012181 QIAquick gel extraction kit Methods 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 206010071390 Resting tremor Diseases 0.000 description 1
- 206010039424 Salivary hypersecretion Diseases 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 208000008630 Sialorrhea Diseases 0.000 description 1
- 206010041349 Somnolence Diseases 0.000 description 1
- 102100036049 T-complex protein 1 subunit gamma Human genes 0.000 description 1
- 108091036066 Three prime untranslated region Proteins 0.000 description 1
- 108700029229 Transcriptional Regulatory Elements Proteins 0.000 description 1
- 108020004566 Transfer RNA Proteins 0.000 description 1
- 108700019146 Transgenes Proteins 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- 241000009298 Trigla lyra Species 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 101000909800 Xenopus laevis Probable N-acetyltransferase camello Proteins 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 208000028752 abnormal posture Diseases 0.000 description 1
- 239000003070 absorption delaying agent Substances 0.000 description 1
- XBJFCYDKBDVADW-UHFFFAOYSA-N acetonitrile;formic acid Chemical compound CC#N.OC=O XBJFCYDKBDVADW-UHFFFAOYSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000009056 active transport Effects 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 230000008848 allosteric regulation Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 229940054051 antipsychotic indole derivative Drugs 0.000 description 1
- 229960004046 apomorphine Drugs 0.000 description 1
- VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 239000003833 bile salt Substances 0.000 description 1
- 229940093761 bile salts Drugs 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 229920000249 biocompatible polymer Polymers 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000006696 biosynthetic metabolic pathway Effects 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- DQXBYHZEEUGOBF-UHFFFAOYSA-N but-3-enoic acid;ethene Chemical compound C=C.OC(=O)CC=C DQXBYHZEEUGOBF-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000007670 carcinogenicity Effects 0.000 description 1
- 231100000260 carcinogenicity Toxicity 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 238000012754 cardiac puncture Methods 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 101150062912 cct3 gene Proteins 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000003822 cell turnover Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 239000013599 cloning vector Substances 0.000 description 1
- 230000004186 co-expression Effects 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000001351 cycling effect Effects 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 230000002638 denervation Effects 0.000 description 1
- 230000030609 dephosphorylation Effects 0.000 description 1
- 238000006209 dephosphorylation reaction Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- 229910001882 dioxygen Inorganic materials 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 229940005501 dopaminergic agent Drugs 0.000 description 1
- 230000003291 dopaminomimetic effect Effects 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 230000003028 elevating effect Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 229960004222 factor ix Drugs 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000010304 firing Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229940014144 folate Drugs 0.000 description 1
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- IECPWNUMDGFDKC-MZJAQBGESA-N fusidic acid Chemical class O[C@@H]([C@@H]12)C[C@H]3\C(=C(/CCC=C(C)C)C(O)=O)[C@@H](OC(C)=O)C[C@]3(C)[C@@]2(C)CC[C@@H]2[C@]1(C)CC[C@@H](O)[C@H]2C IECPWNUMDGFDKC-MZJAQBGESA-N 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 238000001476 gene delivery Methods 0.000 description 1
- 230000002518 glial effect Effects 0.000 description 1
- 230000007387 gliosis Effects 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-L glutamate group Chemical group N[C@@H](CCC(=O)[O-])C(=O)[O-] WHUUTDBJXJRKMK-VKHMYHEASA-L 0.000 description 1
- 230000010243 gut motility Effects 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 102000048937 human GCH1 Human genes 0.000 description 1
- 230000036031 hyperthermia Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 210000003000 inclusion body Anatomy 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 150000002475 indoles Chemical class 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- NBQNWMBBSKPBAY-UHFFFAOYSA-N iodixanol Chemical compound IC=1C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C(I)C=1N(C(=O)C)CC(O)CN(C(C)=O)C1=C(I)C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C1I NBQNWMBBSKPBAY-UHFFFAOYSA-N 0.000 description 1
- 229960004359 iodixanol Drugs 0.000 description 1
- 238000012933 kinetic analysis Methods 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 210000004558 lewy body Anatomy 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 1
- 230000009063 long-term regulation Effects 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000007257 malfunction Effects 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 description 1
- 229960003987 melatonin Drugs 0.000 description 1
- 229960001794 melevodopa Drugs 0.000 description 1
- XBBDACCLCFWBSI-ZETCQYMHSA-N melevodopa Chemical compound COC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 XBBDACCLCFWBSI-ZETCQYMHSA-N 0.000 description 1
- 206010027175 memory impairment Diseases 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 230000004118 muscle contraction Effects 0.000 description 1
- 231100000150 mutagenicity / genotoxicity testing Toxicity 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 239000006218 nasal suppository Substances 0.000 description 1
- 206010061311 nervous system neoplasm Diseases 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 210000001178 neural stem cell Anatomy 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 230000008062 neuronal firing Effects 0.000 description 1
- 230000002981 neuropathic effect Effects 0.000 description 1
- 239000002581 neurotoxin Substances 0.000 description 1
- 231100000618 neurotoxin Toxicity 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 229920000620 organic polymer Polymers 0.000 description 1
- 229940000673 orphan drug Drugs 0.000 description 1
- 239000002859 orphan drug Substances 0.000 description 1
- QUANRIQJNFHVEU-UHFFFAOYSA-N oxirane;propane-1,2,3-triol Chemical compound C1CO1.OCC(O)CO QUANRIQJNFHVEU-UHFFFAOYSA-N 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 210000000578 peripheral nerve Anatomy 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 239000008389 polyethoxylated castor oil Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000004633 polyglycolic acid Substances 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 230000001323 posttranslational effect Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000000541 pulsatile effect Effects 0.000 description 1
- 239000013608 rAAV vector Substances 0.000 description 1
- 238000009790 rate-determining step (RDS) Methods 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000010666 regulation of catalytic activity Effects 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000008085 renal dysfunction Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 235000002020 sage Nutrition 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 210000003523 substantia nigra Anatomy 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 210000000225 synapse Anatomy 0.000 description 1
- 230000005062 synaptic transmission Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000001839 systemic circulation Effects 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000005026 transcription initiation Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 230000021542 voluntary musculoskeletal movement Effects 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Classifications
-
- 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
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/713—Double-stranded nucleic acids or oligonucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/0004—Oxidoreductases (1.)
- C12N9/0071—Oxidoreductases (1.) acting on paired donors with incorporation of molecular oxygen (1.14)
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/78—Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5)
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/88—Lyases (4.)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y114/00—Oxidoreductases acting on paired donors, with incorporation or reduction of molecular oxygen (1.14)
- C12Y114/16—Oxidoreductases acting on paired donors, with incorporation or reduction of molecular oxygen (1.14) with reduced pteridine as one donor, and incorporation of one atom of oxygen (1.14.16)
- C12Y114/16002—Tyrosine 3-monooxygenase (1.14.16.2)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y305/00—Hydrolases acting on carbon-nitrogen bonds, other than peptide bonds (3.5)
- C12Y305/04—Hydrolases acting on carbon-nitrogen bonds, other than peptide bonds (3.5) in cyclic amidines (3.5.4)
- C12Y305/04016—GTP cyclohydrolase I (3.5.4.16)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y402/00—Carbon-oxygen lyases (4.2)
- C12Y402/03—Carbon-oxygen lyases (4.2) acting on phosphates (4.2.3)
- C12Y402/03012—6-Pyruvoyltetrahydropterin synthase (4.2.3.12)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
- C12N2750/00011—Details
- C12N2750/14011—Parvoviridae
- C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
- C12N2750/14141—Use of virus, viral particle or viral elements as a vector
- C12N2750/14143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
- C12N2750/00011—Details
- C12N2750/14011—Parvoviridae
- C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
- C12N2750/14171—Demonstrated in vivo effect
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y114/00—Oxidoreductases acting on paired donors, with incorporation or reduction of molecular oxygen (1.14)
- C12Y114/13—Oxidoreductases acting on paired donors, with incorporation or reduction of molecular oxygen (1.14) with NADH or NADPH as one donor, and incorporation of one atom of oxygen (1.14.13)
- C12Y114/13162—2,5-Diketocamphane 1,2-monooxygenase (1.14.13.162), i.e. camphor 1,2-monooxygenase
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- General Health & Medical Sciences (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Virology (AREA)
- General Chemical & Material Sciences (AREA)
- Psychology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Immunology (AREA)
- Dermatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562200151P | 2015-08-03 | 2015-08-03 | |
| US62/200,151 | 2015-08-03 | ||
| PCT/EP2016/068315 WO2017021359A1 (en) | 2015-08-03 | 2016-08-01 | Systemic synthesis and regulation of l-dopa |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2992511A1 true CA2992511A1 (en) | 2017-02-09 |
Family
ID=56682101
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2992511A Abandoned CA2992511A1 (en) | 2015-08-03 | 2016-08-01 | Systemic synthesis and regulation of l-dopa |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US20190032079A1 (cg-RX-API-DMAC10.html) |
| EP (1) | EP3331570A1 (cg-RX-API-DMAC10.html) |
| JP (1) | JP2018522595A (cg-RX-API-DMAC10.html) |
| KR (1) | KR20180034467A (cg-RX-API-DMAC10.html) |
| CN (1) | CN108136048A (cg-RX-API-DMAC10.html) |
| CA (1) | CA2992511A1 (cg-RX-API-DMAC10.html) |
| RU (1) | RU2018104098A (cg-RX-API-DMAC10.html) |
| WO (1) | WO2017021359A1 (cg-RX-API-DMAC10.html) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB201420139D0 (en) | 2014-11-12 | 2014-12-24 | Ucl Business Plc | Factor IX gene therapy |
| US20210093735A1 (en) * | 2018-04-26 | 2021-04-01 | The University Of North Carolina At Chapel Hill | Methods and compositions for treatment of hemophilia |
| US12313635B2 (en) * | 2018-07-27 | 2025-05-27 | The Regents Of The University Of California | Biomarker for thoracic aortic aneurysm |
| US10842885B2 (en) | 2018-08-20 | 2020-11-24 | Ucl Business Ltd | Factor IX encoding nucleotides |
| GB201813528D0 (en) | 2018-08-20 | 2018-10-03 | Ucl Business Plc | Factor IX encoding nucleotides |
| KR20210151785A (ko) * | 2019-03-13 | 2021-12-14 | 제너레이션 바이오 컴퍼니 | 비바이러스성 dna 벡터 및 fviii 치료제 발현을 위한 이의 용도 |
| KR20210148273A (ko) * | 2019-04-08 | 2021-12-07 | 제네똥 | 근육 발현을 위한 하이브리드 프로모터 |
| GB2587319A (en) * | 2019-08-12 | 2021-03-31 | Healing Genes Llc | Genetic construct |
| EP4081643A1 (en) * | 2019-12-24 | 2022-11-02 | Asklepios Biopharmaceutical, Inc. | Regulatory nucleic acid sequences |
| EP4107259A1 (en) * | 2020-02-18 | 2022-12-28 | Vrije Universiteit Brussel | Novel combination of nucleic acid regulatory elements and methods and uses thereof |
| CN115515646A (zh) | 2020-03-04 | 2022-12-23 | 波赛达治疗公司 | 用于治疗代谢性肝病的组合物和方法 |
| WO2021222653A1 (en) * | 2020-04-29 | 2021-11-04 | Saliogen Therapeutics, Inc. | Compositions and methods for treatment of familial hypercholesterolemia and elevated low-density lipoprotein cholesterol |
| CA3187002A1 (en) * | 2020-07-15 | 2022-01-20 | Danmarks Tekniske Universitet | Therapeutic microbes |
| GB202107473D0 (en) * | 2021-05-26 | 2021-07-07 | Univ Denmark Tech Dtu | Therapeutic microbes |
| IL301255A (en) * | 2020-10-09 | 2023-05-01 | UCB Biopharma SRL | Nucleic acid structures, viral vectors and viral particles |
| GB2601752A (en) * | 2020-12-08 | 2022-06-15 | Maavrx Ltd | Expression vector |
| WO2023012313A1 (en) * | 2021-08-04 | 2023-02-09 | Genethon | Hybrid promoters for gene expression in muscles and in the cns |
| WO2023049874A1 (en) * | 2021-09-24 | 2023-03-30 | Duke University | Compositions for and methods of treating and/or preventing glutaric aciduria type-i |
| CN117106825B (zh) * | 2023-08-28 | 2024-11-01 | 康霖生物科技（杭州）有限公司 | 用于治疗帕金森病的基因治疗载体及其用途 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4522811A (en) | 1982-07-08 | 1985-06-11 | Syntex (U.S.A.) Inc. | Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides |
| DE3681787D1 (de) | 1985-07-05 | 1991-11-07 | Whitehead Biomedical Inst | Expression von fremdem genetischem material in epithelzellen. |
| HK1008049A1 (en) | 1987-09-11 | 1999-04-30 | Whitehead Institute For Biomedical Research | Transduced fibroblasts and use therefor |
| US5399346A (en) | 1989-06-14 | 1995-03-21 | The United States Of America As Represented By The Department Of Health And Human Services | Gene therapy |
| US5677158A (en) | 1995-06-07 | 1997-10-14 | Research Foundation Of State University Of New York | In vitro packaging of adeno-associated virus DNA |
| US6451306B1 (en) | 1998-04-15 | 2002-09-17 | The Regents Of The University Of California | Methods for therapy of neurodegenerative disease of the brain |
| CA2329259C (en) | 1998-05-27 | 2003-08-05 | Avigen, Inc. | Convection-enhanced delivery of aav vectors |
| GB0024550D0 (cg-RX-API-DMAC10.html) * | 2000-10-06 | 2000-11-22 | Oxford Biomedica Ltd | |
| KR100456062B1 (ko) * | 2001-06-18 | 2004-11-08 | 박영식 | 재조합 대장균에 의한 테리딘 화합물의 제조방법 |
| AU2010316982B2 (en) * | 2009-11-09 | 2013-09-12 | Genepod Therapeutics Ab | Novel viral vector construct for neuron specific continuous DOPA synthesis in vivo |
| GB201118636D0 (en) * | 2011-10-28 | 2011-12-07 | Oxford Biomedica Ltd | Nucleotide sequence |
-
2016
- 2016-08-01 WO PCT/EP2016/068315 patent/WO2017021359A1/en not_active Ceased
- 2016-08-01 RU RU2018104098A patent/RU2018104098A/ru not_active Application Discontinuation
- 2016-08-01 US US15/748,145 patent/US20190032079A1/en not_active Abandoned
- 2016-08-01 JP JP2018526302A patent/JP2018522595A/ja active Pending
- 2016-08-01 CA CA2992511A patent/CA2992511A1/en not_active Abandoned
- 2016-08-01 EP EP16750423.2A patent/EP3331570A1/en not_active Withdrawn
- 2016-08-01 CN CN201680045737.2A patent/CN108136048A/zh active Pending
- 2016-08-01 KR KR1020187003356A patent/KR20180034467A/ko not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| RU2018104098A (ru) | 2019-09-06 |
| EP3331570A1 (en) | 2018-06-13 |
| JP2018522595A (ja) | 2018-08-16 |
| CN108136048A (zh) | 2018-06-08 |
| RU2018104098A3 (cg-RX-API-DMAC10.html) | 2020-08-10 |
| KR20180034467A (ko) | 2018-04-04 |
| WO2017021359A1 (en) | 2017-02-09 |
| US20190032079A1 (en) | 2019-01-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20190032079A1 (en) | Systemic synthesis and regulation of l-dopa | |
| AU2010316982B2 (en) | Novel viral vector construct for neuron specific continuous DOPA synthesis in vivo | |
| Alton | Progress and prospects: gene therapy clinical trials (part 1) | |
| US9265843B2 (en) | Treatment of metabolic-related disorders using hypothalamic gene transfer of BDNF and compositions therefor | |
| Choong et al. | Gene therapy for neurological disorders | |
| US12419970B2 (en) | Gene therapy for diseases caused by unbalanced nucleotide pools including mitochondrial DNA depletion syndromes | |
| Georgievska et al. | Regulated delivery of glial cell line-derived neurotrophic factor into rat striatum, using a tetracycline-dependent lentiviral vector | |
| US20200157515A1 (en) | Systems and methods for the treatment of hemoglobinopathies | |
| Sun et al. | Correction of a rat model of Parkinson's disease by coexpression of tyrosine hydroxylase and aromatic amino acid decarboxylase from a helper virus-free herpes simplex virus type 1 vector | |
| KR20110086553A (ko) | 포르포빌리노겐 디아미나아제 유전자 치료 | |
| WO2015138510A1 (en) | Crispr/cas-related methods and compositions for treating leber's congenital amaurosis 10 (lca10) | |
| US20220073951A1 (en) | Systems and methods for the treatment of hemoglobinopathies | |
| Wu et al. | Gene therapy for polygenic or complex diseases | |
| US20250305001A1 (en) | Genetic Construct | |
| US20210077598A1 (en) | Compositions and methods of use thereof for treatment of metabolic deseases and related disorders | |
| Carlsson et al. | Restoration of the striatal dopamine synthesis for Parkinson's disease: viral vector-mediated enzyme replacement strategy | |
| US20200263206A1 (en) | Targeted integration systems and methods for the treatment of hemoglobinopathies | |
| CA3126886A1 (en) | Liver-specific inducible promoters and methods of use thereof | |
| US20240335476A1 (en) | Systems and methods for the treatment of hemoglobinopathies | |
| Leblay et al. | From gene to hope: Rett syndrome and the rise of molecular therapies | |
| US20100303790A1 (en) | Use of biliverdin reductase (bvr) and bvr peptide fragments to treat coronary disorders | |
| Viecelli et al. | Challenges of experimental gene therapy for urea cycle disorders | |
| Laufs et al. | Retrovirus‐Mediated Double Transduction of the GTPCH and PTPS Genes Allows 6‐Pyruvoyltetrahydropterin Synthase‐Deficient Human Fibroblasts to Synthesize and Release Tetrahydrobiopterin | |
| Douglas et al. | Gene Therapy for Parkinson’s Disease | |
| HK1168555B (en) | Novel viral vector construct for neuron specific continuous dopa synthesis in vivo |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20220301 |