ZA200506378B - Diagnosis and treatment of multiple sulfatase deficiency and other using a Formylglycine Generating Enzyme (FGE) - Google Patents

Info

Publication number

ZA200506378B

ZA200506378B ZA200506378A ZA200506378A ZA200506378B ZA 200506378 B ZA200506378 B ZA 200506378B ZA 200506378 A ZA200506378 A ZA 200506378A ZA 200506378 A ZA200506378 A ZA 200506378A ZA 200506378 B ZA200506378 B ZA 200506378B

Authority

ZA

South Africa

Prior art keywords

nucleic acid

sulfatase

fge

arylsulfatase

acid molecule

Prior art date

2003-02-11

Links

• Espacenet
• Global Dossier
• Discuss

• 208000035032 Multiple sulfatase deficiency Diseases 0.000 title claims abstract description 73
• 208000000149 Multiple Sulfatase Deficiency Disease Diseases 0.000 title claims abstract description 72
• 238000011282 treatment Methods 0.000 title claims abstract description 51
• 238000003745 diagnosis Methods 0.000 title claims abstract description 12
• 102100028875 Formylglycine-generating enzyme Human genes 0.000 title claims description 64
• 101710192607 Formylglycine-generating enzyme Proteins 0.000 title claims description 64
• 101710192761 Serine-type anaerobic sulfatase-maturating enzyme Proteins 0.000 title claims description 24
• 108060007951 sulfatase Proteins 0.000 claims abstract description 252
• 102000005262 Sulfatase Human genes 0.000 claims abstract description 244
• 238000000034 method Methods 0.000 claims abstract description 221
• 239000000203 mixture Substances 0.000 claims abstract description 70
• 230000007812 deficiency Effects 0.000 claims abstract description 53
• 150000007523 nucleic acids Chemical class 0.000 claims description 366
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 364
• 102000039446 nucleic acids Human genes 0.000 claims description 352
• 108020004707 nucleic acids Proteins 0.000 claims description 352
• 102000004196 processed proteins & peptides Human genes 0.000 claims description 289
• 229920001184 polypeptide Polymers 0.000 claims description 269
• 210000004027 cell Anatomy 0.000 claims description 258
• 230000014509 gene expression Effects 0.000 claims description 239
• 230000000694 effects Effects 0.000 claims description 198
• 239000002773 nucleotide Substances 0.000 claims description 140
• 125000003729 nucleotide group Chemical group 0.000 claims description 140
• 239000003795 chemical substances by application Substances 0.000 claims description 138
• 239000012634 fragment Substances 0.000 claims description 97
• 230000001965 increasing effect Effects 0.000 claims description 72
• 230000027455 binding Effects 0.000 claims description 68
• 238000009739 binding Methods 0.000 claims description 68
• 241000282414 Homo sapiens Species 0.000 claims description 60
• 125000003275 alpha amino acid group Chemical group 0.000 claims description 54
• 239000013598 vector Substances 0.000 claims description 52
• 239000000523 sample Substances 0.000 claims description 47
• 239000000758 substrate Substances 0.000 claims description 40
• 239000000126 substance Substances 0.000 claims description 36
• 102100022146 Arylsulfatase A Human genes 0.000 claims description 31
• 101000648611 Homo sapiens Formylglycine-generating enzyme Proteins 0.000 claims description 31
• 102100023943 Arylsulfatase L Human genes 0.000 claims description 29
• 102000050003 human SUMF1 Human genes 0.000 claims description 28
• 101710115246 Arylsulfatase L Proteins 0.000 claims description 27
• 108010006140 N-sulfoglucosamine sulfohydrolase Proteins 0.000 claims description 27
• 102100027661 N-sulphoglucosamine sulphohydrolase Human genes 0.000 claims description 27
• 108010087999 Steryl-Sulfatase Proteins 0.000 claims description 27
• 102100038021 Steryl-sulfatase Human genes 0.000 claims description 27
• 102100033887 Arylsulfatase D Human genes 0.000 claims description 26
• 102100033886 Arylsulfatase F Human genes 0.000 claims description 26
• 102100031491 Arylsulfatase B Human genes 0.000 claims description 25
• 101710115233 Arylsulfatase D Proteins 0.000 claims description 25
• 101710115249 Arylsulfatase F Proteins 0.000 claims description 25
• 102100033890 Arylsulfatase G Human genes 0.000 claims description 25
• 101710115232 Arylsulfatase G Proteins 0.000 claims description 25
• 108010036867 Cerebroside-Sulfatase Proteins 0.000 claims description 25
• 108010027520 N-Acetylgalactosamine-4-Sulfatase Proteins 0.000 claims description 25
• 150000001413 amino acids Chemical class 0.000 claims description 25
• 239000013604 expression vector Substances 0.000 claims description 24
• 102100029199 Iduronate 2-sulfatase Human genes 0.000 claims description 23
• 101710096421 Iduronate 2-sulfatase Proteins 0.000 claims description 23
• 238000012360 testing method Methods 0.000 claims description 23
• 102100031688 N-acetylgalactosamine-6-sulfatase Human genes 0.000 claims description 22
• 101710099863 N-acetylgalactosamine-6-sulfatase Proteins 0.000 claims description 22
• 238000002360 preparation method Methods 0.000 claims description 22
• 102000004190 Enzymes Human genes 0.000 claims description 21
• 108090000790 Enzymes Proteins 0.000 claims description 21
• 108010023320 N-acetylglucosamine-6-sulfatase Proteins 0.000 claims description 21
• 108020004705 Codon Proteins 0.000 claims description 20
• 108020004999 messenger RNA Proteins 0.000 claims description 19
• 238000000338 in vitro Methods 0.000 claims description 17
• 230000001594 aberrant effect Effects 0.000 claims description 16
• 102200063048 rs137852846 Human genes 0.000 claims description 14
• 108700028369 Alleles Proteins 0.000 claims description 13
• 238000004519 manufacturing process Methods 0.000 claims description 13
• 239000007787 solid Substances 0.000 claims description 12
• UGJBHEZMOKVTIM-UHFFFAOYSA-N N-formylglycine Chemical compound OC(=O)CNC=O UGJBHEZMOKVTIM-UHFFFAOYSA-N 0.000 claims description 11
• 239000008194 pharmaceutical composition Substances 0.000 claims description 11
• 239000003937 drug carrier Substances 0.000 claims description 10
• 230000002068 genetic effect Effects 0.000 claims description 10
• 239000007790 solid phase Substances 0.000 claims description 9
• 238000000636 Northern blotting Methods 0.000 claims description 8
• 230000002285 radioactive effect Effects 0.000 claims description 8
• 239000013060 biological fluid Substances 0.000 claims description 7
• 210000004962 mammalian cell Anatomy 0.000 claims description 7
• 102200063044 rs137852848 Human genes 0.000 claims description 7
• 230000002163 immunogen Effects 0.000 claims description 6
• 238000012544 monitoring process Methods 0.000 claims description 6
• 102200063046 rs137852849 Human genes 0.000 claims description 6
• 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 claims description 5
• 239000012472 biological sample Substances 0.000 claims description 5
• 102200063054 rs137852852 Human genes 0.000 claims description 5
• 102200063020 rs137852854 Human genes 0.000 claims description 5
• 238000002560 therapeutic procedure Methods 0.000 claims description 5
• 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 claims description 4
• AEMOLEFTQBMNLQ-HNFCZKTMSA-N L-idopyranuronic acid Chemical compound OC1O[C@@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-HNFCZKTMSA-N 0.000 claims description 4
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
• 102200063050 rs137852847 Human genes 0.000 claims description 4
• 101100456896 Drosophila melanogaster metl gene Proteins 0.000 claims description 3
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
• 125000000430 tryptophan group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 3
• 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 2
• 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 2
• 102100023282 N-acetylglucosamine-6-sulfatase Human genes 0.000 claims 9
• 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 5
• 230000004048 modification Effects 0.000 abstract description 15
• 238000012986 modification Methods 0.000 abstract description 15
• 230000004481 post-translational protein modification Effects 0.000 abstract description 7
• 108090000623 proteins and genes Proteins 0.000 description 164
• 239000000047 product Substances 0.000 description 97
• 102000004169 proteins and genes Human genes 0.000 description 78
• 239000002299 complementary DNA Substances 0.000 description 73
• 235000018102 proteins Nutrition 0.000 description 71
• -1 ARSC Proteins 0.000 description 66
• 230000014616 translation Effects 0.000 description 52
• 238000013519 translation Methods 0.000 description 50
• 238000003556 assay Methods 0.000 description 37
• XMTCKNXTTXDPJX-UHFFFAOYSA-N 3-oxoalanine Chemical compound O=CC(N)C(O)=O XMTCKNXTTXDPJX-UHFFFAOYSA-N 0.000 description 33
• 230000035772 mutation Effects 0.000 description 29
• 238000006467 substitution reaction Methods 0.000 description 29
• 235000001014 amino acid Nutrition 0.000 description 28
• 238000013518 transcription Methods 0.000 description 25
• 230000035897 transcription Effects 0.000 description 25
• 108020004414 DNA Proteins 0.000 description 24
• 239000011159 matrix material Substances 0.000 description 24
• 229940024606 amino acid Drugs 0.000 description 22
• 108091034117 Oligonucleotide Proteins 0.000 description 20
• 108091028043 Nucleic acid sequence Proteins 0.000 description 19
• 230000015572 biosynthetic process Effects 0.000 description 19
• 210000002950 fibroblast Anatomy 0.000 description 19
• 239000002502 liposome Substances 0.000 description 19
• 210000001519 tissue Anatomy 0.000 description 18
• 150000001875 compounds Chemical class 0.000 description 17
• 238000009396 hybridization Methods 0.000 description 17
• 230000008685 targeting Effects 0.000 description 17
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 16
• 239000000463 material Substances 0.000 description 16
• 238000003752 polymerase chain reaction Methods 0.000 description 16
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 15
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 15
• 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 Chemical class 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 14
• 239000000074 antisense oligonucleotide Substances 0.000 description 14
• 238000012230 antisense oligonucleotides Methods 0.000 description 14
• 101710132601 Capsid protein Proteins 0.000 description 13
• 241000700605 Viruses Species 0.000 description 13
• 238000011534 incubation Methods 0.000 description 13
• 238000000746 purification Methods 0.000 description 13
• 241000283690 Bos taurus Species 0.000 description 12
• 108091060211 Expressed sequence tag Proteins 0.000 description 12
• 102000056067 N-acetylglucosamine-6-sulfatases Human genes 0.000 description 12
• 239000000872 buffer Substances 0.000 description 12
• 238000012217 deletion Methods 0.000 description 12
• 230000037430 deletion Effects 0.000 description 12
• 239000003814 drug Substances 0.000 description 12
• 230000001105 regulatory effect Effects 0.000 description 12
• 239000000243 solution Substances 0.000 description 12
• 238000001890 transfection Methods 0.000 description 12
• 108020000948 Antisense Oligonucleotides Proteins 0.000 description 11
• 108091026890 Coding region Proteins 0.000 description 11
• 238000007792 addition Methods 0.000 description 11
• 230000000692 anti-sense effect Effects 0.000 description 11
• 239000003153 chemical reaction reagent Substances 0.000 description 11
• 238000001514 detection method Methods 0.000 description 11
• 230000006870 function Effects 0.000 description 11
• 238000001727 in vivo Methods 0.000 description 11
• 239000013612 plasmid Substances 0.000 description 11
• 229920000642 polymer Polymers 0.000 description 11
• 241001430294 unidentified retrovirus Species 0.000 description 11
• 241000699666 Mus <mouse, genus> Species 0.000 description 10
• 238000004458 analytical method Methods 0.000 description 10
• 208000035475 disorder Diseases 0.000 description 10
• 210000002472 endoplasmic reticulum Anatomy 0.000 description 10
• 230000003993 interaction Effects 0.000 description 10
• 238000010361 transduction Methods 0.000 description 10
• 230000026683 transduction Effects 0.000 description 10
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
• 239000007943 implant Substances 0.000 description 9
• 239000003446 ligand Substances 0.000 description 9
• 230000010076 replication Effects 0.000 description 9
• 238000000926 separation method Methods 0.000 description 9
• 238000000672 surface-enhanced laser desorption--ionisation Methods 0.000 description 9
• 210000001550 testis Anatomy 0.000 description 9
• OVRNDRQMDRJTHS-CBQIKETKSA-N N-Acetyl-D-Galactosamine Chemical compound CC(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-CBQIKETKSA-N 0.000 description 8
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
• 239000002253 acid Substances 0.000 description 8
• 239000011230 binding agent Substances 0.000 description 8
• 230000002950 deficient Effects 0.000 description 8
• 230000003828 downregulation Effects 0.000 description 8
• 230000002708 enhancing effect Effects 0.000 description 8
• 239000000284 extract Substances 0.000 description 8
• 150000003839 salts Chemical class 0.000 description 8
• 230000001225 therapeutic effect Effects 0.000 description 8
• 241000702421 Dependoparvovirus Species 0.000 description 7
• 201000011442 Metachromatic leukodystrophy Diseases 0.000 description 7
• 230000000875 corresponding effect Effects 0.000 description 7
• 235000018417 cysteine Nutrition 0.000 description 7
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 7
• 108020001507 fusion proteins Proteins 0.000 description 7
• 102000037865 fusion proteins Human genes 0.000 description 7
• 238000004949 mass spectrometry Methods 0.000 description 7
• 208000022018 mucopolysaccharidosis type 2 Diseases 0.000 description 7
• 238000012216 screening Methods 0.000 description 7
• 238000012163 sequencing technique Methods 0.000 description 7
• 239000011780 sodium chloride Substances 0.000 description 7
• 208000024891 symptom Diseases 0.000 description 7
• 230000003827 upregulation Effects 0.000 description 7
• 239000003981 vehicle Substances 0.000 description 7
• 101710115248 Arylsulfatase A Proteins 0.000 description 6
• 108700039691 Genetic Promoter Regions Proteins 0.000 description 6
• 241001465754 Metazoa Species 0.000 description 6
• 108700008625 Reporter Genes Proteins 0.000 description 6
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 6
• 239000000427 antigen Substances 0.000 description 6
• 108091007433 antigens Proteins 0.000 description 6
• 102000036639 antigens Human genes 0.000 description 6
• 230000015556 catabolic process Effects 0.000 description 6
• 230000008859 change Effects 0.000 description 6
• 238000006243 chemical reaction Methods 0.000 description 6
• 230000000295 complement effect Effects 0.000 description 6
• 230000007423 decrease Effects 0.000 description 6
• 230000003247 decreasing effect Effects 0.000 description 6
• 238000006731 degradation reaction Methods 0.000 description 6
• 230000003834 intracellular effect Effects 0.000 description 6
• 210000001589 microsome Anatomy 0.000 description 6
• 208000012253 mucopolysaccharidosis IVA Diseases 0.000 description 6
• 239000000825 pharmaceutical preparation Substances 0.000 description 6
• 230000001177 retroviral effect Effects 0.000 description 6
• 239000002904 solvent Substances 0.000 description 6
• 241000894007 species Species 0.000 description 6
• 238000013268 sustained release Methods 0.000 description 6
• 239000012730 sustained-release form Substances 0.000 description 6
• 238000003786 synthesis reaction Methods 0.000 description 6
• 238000012546 transfer Methods 0.000 description 6
• 241000701161 unidentified adenovirus Species 0.000 description 6
• 238000011144 upstream manufacturing Methods 0.000 description 6
• HBOMLICNUCNMMY-KJFJCRTCSA-N 1-[(4s,5s)-4-azido-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C)=CN1C1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-KJFJCRTCSA-N 0.000 description 5
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 5
• 239000004475 Arginine Substances 0.000 description 5
• 102000009133 Arylsulfatases Human genes 0.000 description 5
• 108010047041 Complementarity Determining Regions Proteins 0.000 description 5
• 241001529936 Murinae Species 0.000 description 5
• OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 5
• 230000004988 N-glycosylation Effects 0.000 description 5
• 108010038807 Oligopeptides Proteins 0.000 description 5
• 102000015636 Oligopeptides Human genes 0.000 description 5
• 229920002684 Sepharose Polymers 0.000 description 5
• 239000007983 Tris buffer Substances 0.000 description 5
• 230000003213 activating effect Effects 0.000 description 5
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 5
• 235000009697 arginine Nutrition 0.000 description 5
• 230000001580 bacterial effect Effects 0.000 description 5
• 210000004899 c-terminal region Anatomy 0.000 description 5
• 125000003636 chemical group Chemical group 0.000 description 5
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 5
• 238000010367 cloning Methods 0.000 description 5
• 238000005056 compaction Methods 0.000 description 5
• 201000010099 disease Diseases 0.000 description 5
• 238000005516 engineering process Methods 0.000 description 5
• 238000002474 experimental method Methods 0.000 description 5
• 239000013613 expression plasmid Substances 0.000 description 5
• 238000001415 gene therapy Methods 0.000 description 5
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
• 238000003018 immunoassay Methods 0.000 description 5
• 230000001939 inductive effect Effects 0.000 description 5
• 238000001990 intravenous administration Methods 0.000 description 5
• 238000002955 isolation Methods 0.000 description 5
• 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 5
• 230000001404 mediated effect Effects 0.000 description 5
• 239000012528 membrane Substances 0.000 description 5
• 229950006780 n-acetylglucosamine Drugs 0.000 description 5
• 210000002569 neuron Anatomy 0.000 description 5
• 238000004806 packaging method and process Methods 0.000 description 5
• 210000000496 pancreas Anatomy 0.000 description 5
• 239000002245 particle Substances 0.000 description 5
• 230000008569 process Effects 0.000 description 5
• 102000005962 receptors Human genes 0.000 description 5
• 108020003175 receptors Proteins 0.000 description 5
• 230000004044 response Effects 0.000 description 5
• 230000009870 specific binding Effects 0.000 description 5
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 5
• 230000003612 virological effect Effects 0.000 description 5
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
• 208000027219 Deficiency disease Diseases 0.000 description 4
• 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 4
• 108010008177 Fd immunoglobulins Proteins 0.000 description 4
• ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
• 101000975827 Homo sapiens Arylsulfatase L Proteins 0.000 description 4
• 208000002678 Mucopolysaccharidoses Diseases 0.000 description 4
• 206010028095 Mucopolysaccharidosis IV Diseases 0.000 description 4
• 101000648613 Mus musculus Formylglycine-generating enzyme Proteins 0.000 description 4
• 102100038895 Myc proto-oncogene protein Human genes 0.000 description 4
• 101710135898 Myc proto-oncogene protein Proteins 0.000 description 4
• MBLBDJOUHNCFQT-UHFFFAOYSA-N N-acetyl-D-galactosamine Natural products CC(=O)NC(C=O)C(O)C(O)C(O)CO MBLBDJOUHNCFQT-UHFFFAOYSA-N 0.000 description 4
• 108010076504 Protein Sorting Signals Proteins 0.000 description 4
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 4
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 4
• 101710150448 Transcriptional regulator Myc Proteins 0.000 description 4
• 230000001154 acute effect Effects 0.000 description 4
• 125000000539 amino acid group Chemical group 0.000 description 4
• 239000011324 bead Substances 0.000 description 4
• 210000004369 blood Anatomy 0.000 description 4
• 239000008280 blood Substances 0.000 description 4
• 230000003197 catalytic effect Effects 0.000 description 4
• 238000000423 cell based assay Methods 0.000 description 4
• 230000001413 cellular effect Effects 0.000 description 4
• 229920002678 cellulose Polymers 0.000 description 4
• 238000004587 chromatography analysis Methods 0.000 description 4
• 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 4
• 235000014113 dietary fatty acids Nutrition 0.000 description 4
• 210000003527 eukaryotic cell Anatomy 0.000 description 4
• 239000000194 fatty acid Substances 0.000 description 4
• 229930195729 fatty acid Natural products 0.000 description 4
• 150000004665 fatty acids Chemical class 0.000 description 4
• 230000037433 frameshift Effects 0.000 description 4
• 230000004927 fusion Effects 0.000 description 4
• 239000000499 gel Substances 0.000 description 4
• 238000002744 homologous recombination Methods 0.000 description 4
• 230000006801 homologous recombination Effects 0.000 description 4
• 238000010166 immunofluorescence Methods 0.000 description 4
• 238000007918 intramuscular administration Methods 0.000 description 4
• 239000007788 liquid Substances 0.000 description 4
• 230000007774 longterm Effects 0.000 description 4
• 229920002521 macromolecule Polymers 0.000 description 4
• 239000003550 marker Substances 0.000 description 4
• 238000002493 microarray Methods 0.000 description 4
• 238000010369 molecular cloning Methods 0.000 description 4
• 206010028093 mucopolysaccharidosis Diseases 0.000 description 4
• 201000002273 mucopolysaccharidosis II Diseases 0.000 description 4
• 208000000690 mucopolysaccharidosis VI Diseases 0.000 description 4
• 208000025919 mucopolysaccharidosis type 7 Diseases 0.000 description 4
• 238000002823 phage display Methods 0.000 description 4
• 230000004962 physiological condition Effects 0.000 description 4
• 238000011321 prophylaxis Methods 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
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 4
• 235000000346 sugar Nutrition 0.000 description 4
• 229920001059 synthetic polymer Polymers 0.000 description 4
• 230000009261 transgenic effect Effects 0.000 description 4
• 230000005945 translocation Effects 0.000 description 4
• 238000010396 two-hybrid screening Methods 0.000 description 4
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
• 241000894006 Bacteria Species 0.000 description 3
• 241000283707 Capra Species 0.000 description 3
• 108020004635 Complementary DNA Proteins 0.000 description 3
• 102000036364 Cullin Ring E3 Ligases Human genes 0.000 description 3
• 241000701022 Cytomegalovirus Species 0.000 description 3
• 241000588724 Escherichia coli Species 0.000 description 3
• 241000950314 Figura Species 0.000 description 3
• 102220500633 Formylglycine-generating enzyme_P266L_mutation Human genes 0.000 description 3
• 102220500638 Formylglycine-generating enzyme_R224W_mutation Human genes 0.000 description 3
• 102100039556 Galectin-4 Human genes 0.000 description 3
• 108010043121 Green Fluorescent Proteins Proteins 0.000 description 3
• 102000004144 Green Fluorescent Proteins Human genes 0.000 description 3
• 241000238631 Hexapoda Species 0.000 description 3
• 101000901140 Homo sapiens Arylsulfatase A Proteins 0.000 description 3
• 101000925559 Homo sapiens Arylsulfatase D Proteins 0.000 description 3
• 101000925557 Homo sapiens Arylsulfatase F Proteins 0.000 description 3
• 101000608765 Homo sapiens Galectin-4 Proteins 0.000 description 3
• 241000701044 Human gammaherpesvirus 4 Species 0.000 description 3
• DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 3
• DUKURNFHYQXCJG-UHFFFAOYSA-N Lewis A pentasaccharide Natural products OC1C(O)C(O)C(C)OC1OC1C(OC2C(C(O)C(O)C(CO)O2)O)C(NC(C)=O)C(OC2C(C(OC3C(OC(O)C(O)C3O)CO)OC(CO)C2O)O)OC1CO DUKURNFHYQXCJG-UHFFFAOYSA-N 0.000 description 3
• 102000008109 Mixed Function Oxygenases Human genes 0.000 description 3
• 108010074633 Mixed Function Oxygenases Proteins 0.000 description 3
• 241000713869 Moloney murine leukemia virus Species 0.000 description 3
• 108020004711 Nucleic Acid Probes Proteins 0.000 description 3
• 102000035195 Peptidases Human genes 0.000 description 3
• 108091005804 Peptidases Proteins 0.000 description 3
• 108010067902 Peptide Library Proteins 0.000 description 3
• 229920002732 Polyanhydride Polymers 0.000 description 3
• 241000288906 Primates Species 0.000 description 3
• 239000004365 Protease Substances 0.000 description 3
• 102000006010 Protein Disulfide-Isomerase Human genes 0.000 description 3
• 238000002105 Southern blotting Methods 0.000 description 3
• 229930006000 Sucrose Natural products 0.000 description 3
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
• 241000282898 Sus scrofa Species 0.000 description 3
• 208000001001 X-linked ichthyosis Diseases 0.000 description 3
• 230000004913 activation Effects 0.000 description 3
• 239000004480 active ingredient Substances 0.000 description 3
• 230000009286 beneficial effect Effects 0.000 description 3
• 230000004071 biological effect Effects 0.000 description 3
• 229940098773 bovine serum albumin Drugs 0.000 description 3
• 210000004556 brain Anatomy 0.000 description 3
• 125000004432 carbon atom Chemical group C* 0.000 description 3
• 239000001913 cellulose Substances 0.000 description 3
• 235000010980 cellulose Nutrition 0.000 description 3
• 238000011210 chromatographic step Methods 0.000 description 3
• 210000000349 chromosome Anatomy 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 108091036078 conserved sequence Proteins 0.000 description 3
• 229920001577 copolymer Polymers 0.000 description 3
• 238000011161 development Methods 0.000 description 3
• 230000018109 developmental process Effects 0.000 description 3
• 239000003085 diluting agent Substances 0.000 description 3
• 229940079593 drug Drugs 0.000 description 3
• 210000001671 embryonic stem cell Anatomy 0.000 description 3
• 230000002349 favourable effect Effects 0.000 description 3
• 238000009472 formulation Methods 0.000 description 3
• 239000005090 green fluorescent protein Substances 0.000 description 3
• 210000002216 heart Anatomy 0.000 description 3
• 210000005260 human cell Anatomy 0.000 description 3
• 239000000017 hydrogel Substances 0.000 description 3
• 206010021198 ichthyosis Diseases 0.000 description 3
• 230000001900 immune effect Effects 0.000 description 3
• 238000010324 immunological assay Methods 0.000 description 3
• 230000001976 improved effect Effects 0.000 description 3
• 238000000099 in vitro assay Methods 0.000 description 3
• 230000005764 inhibitory process Effects 0.000 description 3
• 239000007924 injection Substances 0.000 description 3
• 238000002347 injection Methods 0.000 description 3
• 210000003734 kidney Anatomy 0.000 description 3
• 150000002632 lipids Chemical class 0.000 description 3
• 210000004185 liver Anatomy 0.000 description 3
• 230000014759 maintenance of location Effects 0.000 description 3
• 238000012775 microarray technology Methods 0.000 description 3
• 231100000252 nontoxic Toxicity 0.000 description 3
• 230000003000 nontoxic effect Effects 0.000 description 3
• 239000002853 nucleic acid probe Substances 0.000 description 3
• 150000002894 organic compounds Chemical class 0.000 description 3
• 230000003647 oxidation Effects 0.000 description 3
• 238000007254 oxidation reaction Methods 0.000 description 3
• 229940088507 permax Drugs 0.000 description 3
• ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 3
• 108020003519 protein disulfide isomerase Proteins 0.000 description 3
• 208000026079 recessive X-linked ichthyosis Diseases 0.000 description 3
• 230000002441 reversible effect Effects 0.000 description 3
• 102220001053 rs137852845 Human genes 0.000 description 3
• 102200063052 rs137852853 Human genes 0.000 description 3
• 102200063017 rs200142963 Human genes 0.000 description 3
• 239000007858 starting material Substances 0.000 description 3
• 230000004960 subcellular localization Effects 0.000 description 3
• 238000007920 subcutaneous administration Methods 0.000 description 3
• 239000005720 sucrose Substances 0.000 description 3
• 239000006228 supernatant Substances 0.000 description 3
• 239000000725 suspension Substances 0.000 description 3
• 238000010399 three-hybrid screening Methods 0.000 description 3
• 238000005406 washing Methods 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
• PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
• 108091027075 5S-rRNA precursor Proteins 0.000 description 2
• FVFVNNKYKYZTJU-UHFFFAOYSA-N 6-chloro-1,3,5-triazine-2,4-diamine Chemical group NC1=NC(N)=NC(Cl)=N1 FVFVNNKYKYZTJU-UHFFFAOYSA-N 0.000 description 2
• FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 2
• 108010088751 Albumins Proteins 0.000 description 2
• 102000009027 Albumins Human genes 0.000 description 2
• 102100026277 Alpha-galactosidase A Human genes 0.000 description 2
• 108010032595 Antibody Binding Sites Proteins 0.000 description 2
• DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
• 206010006187 Breast cancer Diseases 0.000 description 2
• 108090000565 Capsid Proteins Proteins 0.000 description 2
• 241001409861 Caulobacter vibrioides CB15 Species 0.000 description 2
• 241001644925 Corynebacterium efficiens Species 0.000 description 2
• 241000699800 Cricetinae Species 0.000 description 2
• 241000252867 Cupriavidus metallidurans Species 0.000 description 2
• 241000255925 Diptera Species 0.000 description 2
• 108700039887 Essential Genes Proteins 0.000 description 2
• 108700024394 Exon Proteins 0.000 description 2
• 102220500614 Formylglycine-generating enzyme_N259I_mutation Human genes 0.000 description 2
• 108700028146 Genetic Enhancer Elements Proteins 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• 229920002683 Glycosaminoglycan Polymers 0.000 description 2
• 101000718525 Homo sapiens Alpha-galactosidase A Proteins 0.000 description 2
• 101000923070 Homo sapiens Arylsulfatase B Proteins 0.000 description 2
• 101000925538 Homo sapiens Arylsulfatase G Proteins 0.000 description 2
• 101000840540 Homo sapiens Iduronate 2-sulfatase Proteins 0.000 description 2
• 101000661600 Homo sapiens Steryl-sulfatase Proteins 0.000 description 2
• 241000725303 Human immunodeficiency virus Species 0.000 description 2
• 102000018251 Hypoxanthine Phosphoribosyltransferase Human genes 0.000 description 2
• 108010091358 Hypoxanthine Phosphoribosyltransferase Proteins 0.000 description 2
• ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 2
• FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
• 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 2
• 102000018697 Membrane Proteins Human genes 0.000 description 2
• 108010052285 Membrane Proteins Proteins 0.000 description 2
• 208000024556 Mendelian disease Diseases 0.000 description 2
• 241000589195 Mesorhizobium loti Species 0.000 description 2
• 241000190905 Microscilla Species 0.000 description 2
• 206010056893 Mucopolysaccharidosis VII Diseases 0.000 description 2
• 208000025797 Mucopolysaccharidosis type 4A Diseases 0.000 description 2
• 208000025915 Mucopolysaccharidosis type 6 Diseases 0.000 description 2
• OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 2
• MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 description 2
• 206010028980 Neoplasm Diseases 0.000 description 2
• 241000233540 Novosphingobium aromaticivorans Species 0.000 description 2
• 229910019142 PO4 Inorganic materials 0.000 description 2
• 241001631646 Papillomaviridae Species 0.000 description 2
• 241000930992 Paraburkholderia fungorum Species 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 229920001305 Poly(isodecyl(meth)acrylate) Polymers 0.000 description 2
• 229920002319 Poly(methyl acrylate) Polymers 0.000 description 2
• 239000004952 Polyamide Substances 0.000 description 2
• 239000004793 Polystyrene Substances 0.000 description 2
• 241000192137 Prochlorococcus marinus Species 0.000 description 2
• ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
• 241000320117 Pseudomonas putida KT2440 Species 0.000 description 2
• 108020005067 RNA Splice Sites Proteins 0.000 description 2
• 102000018120 Recombinases Human genes 0.000 description 2
• 108010091086 Recombinases Proteins 0.000 description 2
• 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
• 241000589196 Sinorhizobium meliloti Species 0.000 description 2
• 201000001828 Sly syndrome Diseases 0.000 description 2
• 229930182558 Sterol Natural products 0.000 description 2
• 241000187432 Streptomyces coelicolor Species 0.000 description 2
• 108700026226 TATA Box Proteins 0.000 description 2
• 241000255588 Tephritidae Species 0.000 description 2
• 102000040945 Transcription factor Human genes 0.000 description 2
• 108091023040 Transcription factor Proteins 0.000 description 2
• 108700019146 Transgenes Proteins 0.000 description 2
• 102000004142 Trypsin Human genes 0.000 description 2
• 108090000631 Trypsin Proteins 0.000 description 2
• QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
• KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Chemical compound CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• 239000012190 activator Substances 0.000 description 2
• 238000001042 affinity chromatography Methods 0.000 description 2
• 125000003172 aldehyde group Chemical group 0.000 description 2
• 150000001299 aldehydes Chemical class 0.000 description 2
• 229940072056 alginate Drugs 0.000 description 2
• 235000010443 alginic acid Nutrition 0.000 description 2
• 229920000615 alginic acid Polymers 0.000 description 2
• 125000002947 alkylene group Chemical group 0.000 description 2
• 229940019748 antifibrinolytic proteinase inhibitors Drugs 0.000 description 2
• 230000000890 antigenic effect Effects 0.000 description 2
• 238000003491 array Methods 0.000 description 2
• 235000009582 asparagine Nutrition 0.000 description 2
• 229960001230 asparagine Drugs 0.000 description 2
• 239000000227 bioadhesive Substances 0.000 description 2
• 229920002988 biodegradable polymer Polymers 0.000 description 2
• 239000004621 biodegradable polymer Substances 0.000 description 2
• 229960002685 biotin Drugs 0.000 description 2
• 239000011616 biotin Substances 0.000 description 2
• 210000004204 blood vessel Anatomy 0.000 description 2
• 210000001185 bone marrow Anatomy 0.000 description 2
• 201000011510 cancer Diseases 0.000 description 2
• 239000002775 capsule Substances 0.000 description 2
• 238000004113 cell culture Methods 0.000 description 2
• 230000003915 cell function Effects 0.000 description 2
• 210000000170 cell membrane Anatomy 0.000 description 2
• 108091092356 cellular DNA Proteins 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
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
• 238000003776 cleavage reaction Methods 0.000 description 2
• 239000013599 cloning vector Substances 0.000 description 2
• 238000000576 coating method Methods 0.000 description 2
• 238000001246 colloidal dispersion Methods 0.000 description 2
• 201000010897 colon adenocarcinoma Diseases 0.000 description 2
• 208000029742 colonic neoplasm Diseases 0.000 description 2
• 238000010276 construction Methods 0.000 description 2
• 230000000120 cytopathologic effect Effects 0.000 description 2
• 210000000805 cytoplasm Anatomy 0.000 description 2
• 238000007257 deesterification reaction Methods 0.000 description 2
• 230000007547 defect Effects 0.000 description 2
• 238000002716 delivery method Methods 0.000 description 2
• 238000013461 design Methods 0.000 description 2
• 238000003795 desorption Methods 0.000 description 2
• 239000003599 detergent Substances 0.000 description 2
• 238000009792 diffusion process Methods 0.000 description 2
• 238000009826 distribution Methods 0.000 description 2
• 230000008030 elimination Effects 0.000 description 2
• 238000003379 elimination reaction Methods 0.000 description 2
• 238000010828 elution Methods 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• 239000003623 enhancer Substances 0.000 description 2
• 210000002919 epithelial cell Anatomy 0.000 description 2
• 239000000945 filler Substances 0.000 description 2
• 238000002866 fluorescence resonance energy transfer Methods 0.000 description 2
• 239000011521 glass Substances 0.000 description 2
• 230000036541 health Effects 0.000 description 2
• 238000013537 high throughput screening Methods 0.000 description 2
• 102000043401 human ARSB Human genes 0.000 description 2
• 102000043439 human ARSD Human genes 0.000 description 2
• 102000050182 human ARSG Human genes 0.000 description 2
• 238000002513 implantation Methods 0.000 description 2
• 238000010348 incorporation Methods 0.000 description 2
• 230000006698 induction Effects 0.000 description 2
• 208000015181 infectious disease Diseases 0.000 description 2
• 239000004615 ingredient Substances 0.000 description 2
• 239000003112 inhibitor Substances 0.000 description 2
• 230000002401 inhibitory effect Effects 0.000 description 2
• 230000000977 initiatory effect Effects 0.000 description 2
• 238000003780 insertion Methods 0.000 description 2
• 230000037431 insertion Effects 0.000 description 2
• 230000010354 integration Effects 0.000 description 2
• 238000000534 ion trap mass spectrometry Methods 0.000 description 2
• 150000002500 ions Chemical class 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
• 208000032839 leukemia Diseases 0.000 description 2
• 210000004072 lung Anatomy 0.000 description 2
• 238000005259 measurement Methods 0.000 description 2
• 238000000691 measurement method Methods 0.000 description 2
• 229930182817 methionine Natural products 0.000 description 2
• 239000000693 micelle Substances 0.000 description 2
• 239000003094 microcapsule Substances 0.000 description 2
• 239000011859 microparticle Substances 0.000 description 2
• 208000005340 mucopolysaccharidosis III Diseases 0.000 description 2
• 208000011045 mucopolysaccharidosis type 3 Diseases 0.000 description 2
• 208000010978 mucopolysaccharidosis type 4 Diseases 0.000 description 2
• 229920005615 natural polymer Polymers 0.000 description 2
• 229930014626 natural product Natural products 0.000 description 2
• 230000007935 neutral effect Effects 0.000 description 2
• 229920001220 nitrocellulos Polymers 0.000 description 2
• 239000000346 nonvolatile oil Substances 0.000 description 2
• 238000007899 nucleic acid hybridization Methods 0.000 description 2
• 229940124276 oligodeoxyribonucleotide Drugs 0.000 description 2
• 230000003287 optical effect Effects 0.000 description 2
• 230000002018 overexpression Effects 0.000 description 2
• 230000036961 partial effect Effects 0.000 description 2
• 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
• 230000000144 pharmacologic effect Effects 0.000 description 2
• 239000012071 phase Substances 0.000 description 2
• 150000004713 phosphodiesters Chemical class 0.000 description 2
• 230000001766 physiological effect Effects 0.000 description 2
• 229920001490 poly(butyl methacrylate) polymer Polymers 0.000 description 2
• 229920000212 poly(isobutyl acrylate) Polymers 0.000 description 2
• 229920000196 poly(lauryl methacrylate) Polymers 0.000 description 2
• 229920000184 poly(octadecyl acrylate) Polymers 0.000 description 2
• 229920001281 polyalkylene Polymers 0.000 description 2
• 229920002647 polyamide Polymers 0.000 description 2
• 239000004417 polycarbonate Substances 0.000 description 2
• 229920000129 polyhexylmethacrylate Polymers 0.000 description 2
• 229920000197 polyisopropyl acrylate Polymers 0.000 description 2
• 229920000182 polyphenyl methacrylate Polymers 0.000 description 2
• 229920002223 polystyrene Polymers 0.000 description 2
• 229920002635 polyurethane Polymers 0.000 description 2
• 239000004814 polyurethane Substances 0.000 description 2
• 229920002451 polyvinyl alcohol Polymers 0.000 description 2
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
• 239000002243 precursor Substances 0.000 description 2
• 235000019419 proteases Nutrition 0.000 description 2
• 238000000159 protein binding assay Methods 0.000 description 2
• 230000017854 proteolysis Effects 0.000 description 2
• RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 2
• 238000011084 recovery Methods 0.000 description 2
• 230000002829 reductive effect Effects 0.000 description 2
• 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 2
• 238000011160 research Methods 0.000 description 2
• 238000004007 reversed phase HPLC Methods 0.000 description 2
• 102220001052 rs137852844 Human genes 0.000 description 2
• 230000007017 scission Effects 0.000 description 2
• 238000002741 site-directed mutagenesis Methods 0.000 description 2
• 210000001626 skin fibroblast Anatomy 0.000 description 2
• 210000001082 somatic cell Anatomy 0.000 description 2
• 238000001228 spectrum Methods 0.000 description 2
• 238000010561 standard procedure Methods 0.000 description 2
• 150000003432 sterols Chemical class 0.000 description 2
• 235000003702 sterols Nutrition 0.000 description 2
• 150000008163 sugars Chemical class 0.000 description 2
• 229910052717 sulfur Inorganic materials 0.000 description 2
• 239000003826 tablet Substances 0.000 description 2
• 125000003396 thiol group Chemical group [H]S* 0.000 description 2
• 230000032258 transport Effects 0.000 description 2
• 239000012588 trypsin Substances 0.000 description 2
• 201000008827 tuberculosis Diseases 0.000 description 2
• 241001529453 unidentified herpesvirus Species 0.000 description 2
• 210000002700 urine Anatomy 0.000 description 2
• 230000002792 vascular Effects 0.000 description 2
• 210000003556 vascular endothelial cell Anatomy 0.000 description 2
• 229920002554 vinyl polymer Polymers 0.000 description 2
• 239000013603 viral vector Substances 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
• LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
• WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
• RPZANUYHRMRTTE-UHFFFAOYSA-N 2,3,4-trimethoxy-6-(methoxymethyl)-5-[3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxyoxane;1-[[3,4,5-tris(2-hydroxybutoxy)-6-[4,5,6-tris(2-hydroxybutoxy)-2-(2-hydroxybutoxymethyl)oxan-3-yl]oxyoxan-2-yl]methoxy]butan-2-ol Chemical compound COC1C(OC)C(OC)C(COC)OC1OC1C(OC)C(OC)C(OC)OC1COC.CCC(O)COC1C(OCC(O)CC)C(OCC(O)CC)C(COCC(O)CC)OC1OC1C(OCC(O)CC)C(OCC(O)CC)C(OCC(O)CC)OC1COCC(O)CC RPZANUYHRMRTTE-UHFFFAOYSA-N 0.000 description 1
• LDGWQMRUWMSZIU-LQDDAWAPSA-M 2,3-bis[(z)-octadec-9-enoxy]propyl-trimethylazanium;chloride Chemical compound [Cl-].CCCCCCCC\C=C/CCCCCCCCOCC(C[N+](C)(C)C)OCCCCCCCC\C=C/CCCCCCCC LDGWQMRUWMSZIU-LQDDAWAPSA-M 0.000 description 1
• BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
• LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
• HVCOBJNICQPDBP-UHFFFAOYSA-N 3-[3-[3,5-dihydroxy-6-methyl-4-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid;hydrate Chemical compound O.OC1C(OC(CC(=O)OC(CCCCCCC)CC(O)=O)CCCCCCC)OC(C)C(O)C1OC1C(O)C(O)C(O)C(C)O1 HVCOBJNICQPDBP-UHFFFAOYSA-N 0.000 description 1
• 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 description 1
• QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
• WRDABNWSWOHGMS-UHFFFAOYSA-N AEBSF hydrochloride Chemical compound Cl.NCCC1=CC=C(S(F)(=O)=O)C=C1 WRDABNWSWOHGMS-UHFFFAOYSA-N 0.000 description 1
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical class CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 1
• HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
• 241000251468 Actinopterygii Species 0.000 description 1
• 102000055025 Adenosine deaminases Human genes 0.000 description 1
• 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
• 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
• 241000256182 Anopheles gambiae Species 0.000 description 1
• 108010039627 Aprotinin Proteins 0.000 description 1
• 241000972773 Aulopiformes Species 0.000 description 1
• VGGGPCQERPFHOB-MCIONIFRSA-N Bestatin Chemical compound CC(C)C[C@H](C(O)=O)NC(=O)[C@@H](O)[C@H](N)CC1=CC=CC=C1 VGGGPCQERPFHOB-MCIONIFRSA-N 0.000 description 1
• VGGGPCQERPFHOB-UHFFFAOYSA-N Bestatin Natural products CC(C)CC(C(O)=O)NC(=O)C(O)C(N)CC1=CC=CC=C1 VGGGPCQERPFHOB-UHFFFAOYSA-N 0.000 description 1
• 208000026310 Breast neoplasm Diseases 0.000 description 1
• 241000282465 Canis Species 0.000 description 1
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
• 201000009030 Carcinoma Diseases 0.000 description 1
• 102000053642 Catalytic RNA Human genes 0.000 description 1
• 108090000994 Catalytic RNA Proteins 0.000 description 1
• 102000000844 Cell Surface Receptors Human genes 0.000 description 1
• 108010001857 Cell Surface Receptors Proteins 0.000 description 1
• 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
• DQEFEBPAPFSJLV-UHFFFAOYSA-N Cellulose propionate Chemical compound CCC(=O)OCC1OC(OC(=O)CC)C(OC(=O)CC)C(OC(=O)CC)C1OC1C(OC(=O)CC)C(OC(=O)CC)C(OC(=O)CC)C(COC(=O)CC)O1 DQEFEBPAPFSJLV-UHFFFAOYSA-N 0.000 description 1
• 229920002284 Cellulose triacetate Polymers 0.000 description 1
• 102000009265 Cerebrospinal Fluid Proteins Human genes 0.000 description 1
• 108010073496 Cerebrospinal Fluid Proteins Proteins 0.000 description 1
• 102100023321 Ceruloplasmin Human genes 0.000 description 1
• 229920001661 Chitosan Polymers 0.000 description 1
• VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
• 102000008186 Collagen Human genes 0.000 description 1
• 108010035532 Collagen Proteins 0.000 description 1
• 108010062580 Concanavalin A Proteins 0.000 description 1
• HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
• 102000053602 DNA Human genes 0.000 description 1
• 238000000018 DNA microarray Methods 0.000 description 1
• 239000003298 DNA probe Substances 0.000 description 1
• 230000004568 DNA-binding Effects 0.000 description 1
• 241000252212 Danio rerio Species 0.000 description 1
• 229920002307 Dextran Polymers 0.000 description 1
• BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
• MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
• 241000255601 Drosophila melanogaster Species 0.000 description 1
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
• 101710201734 E3 protein Proteins 0.000 description 1
• 241000196324 Embryophyta Species 0.000 description 1
• 102100031780 Endonuclease Human genes 0.000 description 1
• 108010042407 Endonucleases Proteins 0.000 description 1
• 241000991587 Enterovirus C Species 0.000 description 1
• 241000701959 Escherichia virus Lambda Species 0.000 description 1
• 239000001856 Ethyl cellulose Substances 0.000 description 1
• ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
• 241000206602 Eukaryota Species 0.000 description 1
• YPZRHBJKEMOYQH-UYBVJOGSSA-N FADH2 Chemical compound C1=NC2=C(N)N=CN=C2N1[C@@H]([C@H](O)[C@@H]1O)O[C@@H]1COP(O)(=O)OP(O)(=O)OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C(NC(=O)NC2=O)=C2NC2=C1C=C(C)C(C)=C2 YPZRHBJKEMOYQH-UYBVJOGSSA-N 0.000 description 1
• 229920001917 Ficoll Polymers 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• 108010024636 Glutathione Proteins 0.000 description 1
• 108010053070 Glutathione Disulfide Proteins 0.000 description 1
• 229930186217 Glycolipid Natural products 0.000 description 1
• 102000003886 Glycoproteins Human genes 0.000 description 1
• 108090000288 Glycoproteins Proteins 0.000 description 1
• 241000713858 Harvey murine sarcoma virus Species 0.000 description 1
• 108010033040 Histones Proteins 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 101000935587 Homo sapiens Flavin reductase (NADPH) Proteins 0.000 description 1
• 101001066305 Homo sapiens N-acetylgalactosamine-6-sulfatase Proteins 0.000 description 1
• 101000829992 Homo sapiens N-acetylglucosamine-6-sulfatase Proteins 0.000 description 1
• 101000591312 Homo sapiens Putative MORF4 family-associated protein 1-like protein UPP Proteins 0.000 description 1
• 241000701024 Human betaherpesvirus 5 Species 0.000 description 1
• 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
• 206010062767 Hypophysitis Diseases 0.000 description 1
• 108060003951 Immunoglobulin Proteins 0.000 description 1
• 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
• 108091092195 Intron Proteins 0.000 description 1
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
• AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
• KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
• GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
• 108060001084 Luciferase Proteins 0.000 description 1
• 239000005089 Luciferase Substances 0.000 description 1
• 208000015439 Lysosomal storage disease Diseases 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• 102000003792 Metallothionein Human genes 0.000 description 1
• 108090000157 Metallothionein Proteins 0.000 description 1
• CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 1
• 208000019695 Migraine disease Diseases 0.000 description 1
• 102000005431 Molecular Chaperones Human genes 0.000 description 1
• 108010006519 Molecular Chaperones Proteins 0.000 description 1
• 206010056886 Mucopolysaccharidosis I Diseases 0.000 description 1
• 241000204795 Muraena helena Species 0.000 description 1
• 241000711408 Murine respirovirus Species 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• 108010083674 Myelin Proteins Proteins 0.000 description 1
• 102000006386 Myelin Proteins Human genes 0.000 description 1
• 239000000020 Nitrocellulose Substances 0.000 description 1
• 101710163270 Nuclease Proteins 0.000 description 1
• 239000004677 Nylon Substances 0.000 description 1
• 239000005642 Oleic acid Substances 0.000 description 1
• ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
• 108020005187 Oligonucleotide Probes Proteins 0.000 description 1
• 206010033128 Ovarian cancer Diseases 0.000 description 1
• 102000002508 Peptide Elongation Factors Human genes 0.000 description 1
• 108010068204 Peptide Elongation Factors Proteins 0.000 description 1
• 102000003992 Peroxidases Human genes 0.000 description 1
• 108010002747 Pfu DNA polymerase Proteins 0.000 description 1
• 108091000080 Phosphotransferase Proteins 0.000 description 1
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
• 229920002845 Poly(methacrylic acid) Polymers 0.000 description 1
• 239000004698 Polyethylene Substances 0.000 description 1
• 229920000954 Polyglycolide Polymers 0.000 description 1
• 108010039918 Polylysine Proteins 0.000 description 1
• 241001505332 Polyomavirus sp. Species 0.000 description 1
• 229920001710 Polyorthoester Polymers 0.000 description 1
• 239000004743 Polypropylene Substances 0.000 description 1
• 208000020853 Progressive neurologic deterioration Diseases 0.000 description 1
• 102100034096 Putative MORF4 family-associated protein 1-like protein UPP Human genes 0.000 description 1
• 101710185720 Putative ethidium bromide resistance protein Proteins 0.000 description 1
• 102000013009 Pyruvate Kinase Human genes 0.000 description 1
• 108020005115 Pyruvate Kinase Proteins 0.000 description 1
• 208000033787 Rare developmental defect during embryogenesis Diseases 0.000 description 1
• 108020004511 Recombinant DNA Proteins 0.000 description 1
• 108091028664 Ribonucleotide Proteins 0.000 description 1
• PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
• 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
• 241000714474 Rous sarcoma virus Species 0.000 description 1
• 239000012722 SDS sample buffer Substances 0.000 description 1
• 206010039491 Sarcoma Diseases 0.000 description 1
• 238000012300 Sequence Analysis Methods 0.000 description 1
• 241000700584 Simplexvirus Species 0.000 description 1
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
• 229920002125 Sokalan® Polymers 0.000 description 1
• 238000000692 Student's t-test Methods 0.000 description 1
• 206010042566 Superinfection Diseases 0.000 description 1
• 102000017299 Synapsin-1 Human genes 0.000 description 1
• 108050005241 Synapsin-1 Proteins 0.000 description 1
• 108020005038 Terminator Codon Proteins 0.000 description 1
• RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 1
• 108091036066 Three prime untranslated region Proteins 0.000 description 1
• AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
• 239000004473 Threonine Substances 0.000 description 1
• 102000006601 Thymidine Kinase Human genes 0.000 description 1
• 108020004440 Thymidine kinase Proteins 0.000 description 1
• 229920004890 Triton X-100 Polymers 0.000 description 1
• 239000013504 Triton X-100 Substances 0.000 description 1
• 241000700618 Vaccinia virus Species 0.000 description 1
• 108020000999 Viral RNA Proteins 0.000 description 1
• 241000269368 Xenopus laevis Species 0.000 description 1
• 241000269457 Xenopus tropicalis Species 0.000 description 1
• 229920002494 Zein Polymers 0.000 description 1
• NNLVGZFZQQXQNW-ADJNRHBOSA-N [(2r,3r,4s,5r,6s)-4,5-diacetyloxy-3-[(2s,3r,4s,5r,6r)-3,4,5-triacetyloxy-6-(acetyloxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6s)-4,5,6-triacetyloxy-2-(acetyloxymethyl)oxan-3-yl]oxyoxan-2-yl]methyl acetate Chemical compound O([C@@H]1O[C@@H]([C@H]([C@H](OC(C)=O)[C@H]1OC(C)=O)O[C@H]1[C@@H]([C@@H](OC(C)=O)[C@H](OC(C)=O)[C@@H](COC(C)=O)O1)OC(C)=O)COC(=O)C)[C@@H]1[C@@H](COC(C)=O)O[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1OC(C)=O NNLVGZFZQQXQNW-ADJNRHBOSA-N 0.000 description 1
• NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 230000010933 acylation Effects 0.000 description 1
• 238000005917 acylation reaction Methods 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 230000000996 additive effect Effects 0.000 description 1
• 210000004100 adrenal gland Anatomy 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 235000004279 alanine Nutrition 0.000 description 1
• 229920013820 alkyl cellulose Polymers 0.000 description 1
• 125000000217 alkyl group Chemical group 0.000 description 1
• 125000005600 alkyl phosphonate group Chemical group 0.000 description 1
• 230000029936 alkylation Effects 0.000 description 1
• 238000005804 alkylation reaction Methods 0.000 description 1
• HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
• 230000004075 alteration Effects 0.000 description 1
• PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 229910000323 aluminium silicate Inorganic materials 0.000 description 1
• 150000001412 amines Chemical class 0.000 description 1
• 230000003321 amplification Effects 0.000 description 1
• 150000001450 anions Chemical class 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 229940088710 antibiotic agent Drugs 0.000 description 1
• 239000004599 antimicrobial Substances 0.000 description 1
• 229960004405 aprotinin Drugs 0.000 description 1
• PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 1
• PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
• 239000000823 artificial membrane Substances 0.000 description 1
• 125000003118 aryl group Chemical group 0.000 description 1
• 125000004429 atom Chemical group 0.000 description 1
• 230000002358 autolytic effect Effects 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• 229960000686 benzalkonium chloride Drugs 0.000 description 1
• CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
• SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
• 238000002799 binding type assay Methods 0.000 description 1
• 238000001574 biopsy Methods 0.000 description 1
• 235000020958 biotin Nutrition 0.000 description 1
• 210000000988 bone and bone Anatomy 0.000 description 1
• 210000002798 bone marrow cell Anatomy 0.000 description 1
• KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
• 239000004327 boric acid Substances 0.000 description 1
• 210000000481 breast Anatomy 0.000 description 1
• 125000001246 bromo group Chemical group Br* 0.000 description 1
• 239000006172 buffering agent Substances 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
• 235000019437 butane-1,3-diol Nutrition 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• 229910000389 calcium phosphate Inorganic materials 0.000 description 1
• 235000011010 calcium phosphates Nutrition 0.000 description 1
• 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
• 150000001720 carbohydrates Chemical class 0.000 description 1
• 229910052799 carbon Inorganic materials 0.000 description 1
• 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
• 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
• 210000000845 cartilage Anatomy 0.000 description 1
• 239000005018 casein Substances 0.000 description 1
• BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
• 235000021240 caseins Nutrition 0.000 description 1
• 125000002091 cationic group Chemical group 0.000 description 1
• 239000013592 cell lysate Substances 0.000 description 1
• 210000003855 cell nucleus Anatomy 0.000 description 1
• 230000030570 cellular localization Effects 0.000 description 1
• 230000033077 cellular process Effects 0.000 description 1
• 229920002301 cellulose acetate Polymers 0.000 description 1
• 229920006217 cellulose acetate butyrate Polymers 0.000 description 1
• 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
• 229920003086 cellulose ether Polymers 0.000 description 1
• 229920006218 cellulose propionate Polymers 0.000 description 1
• 210000003169 central nervous system Anatomy 0.000 description 1
• 230000003196 chaotropic effect Effects 0.000 description 1
• 238000007385 chemical modification Methods 0.000 description 1
• 229960004926 chlorobutanol Drugs 0.000 description 1
• 235000012000 cholesterol Nutrition 0.000 description 1
• 150000001840 cholesterol esters Chemical class 0.000 description 1
• 208000001020 chondrodysplasia punctata Diseases 0.000 description 1
• 229910052804 chromium Inorganic materials 0.000 description 1
• 239000011651 chromium Substances 0.000 description 1
• 230000002759 chromosomal effect Effects 0.000 description 1
• 238000011260 co-administration Methods 0.000 description 1
• 230000008045 co-localization Effects 0.000 description 1
• 229920001436 collagen Polymers 0.000 description 1
• 239000000084 colloidal system Substances 0.000 description 1
• 210000001072 colon Anatomy 0.000 description 1
• 230000024203 complement activation Effects 0.000 description 1
• 239000007891 compressed tablet Substances 0.000 description 1
• 238000000205 computational method Methods 0.000 description 1
• 210000002808 connective tissue Anatomy 0.000 description 1
• 238000002508 contact lithography Methods 0.000 description 1
• 239000000356 contaminant Substances 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 230000002596 correlated effect Effects 0.000 description 1
• 230000008878 coupling Effects 0.000 description 1
• 239000007822 coupling agent Substances 0.000 description 1
• 238000010168 coupling process Methods 0.000 description 1
• 238000005859 coupling reaction Methods 0.000 description 1
• 125000004122 cyclic group Chemical group 0.000 description 1
• 230000001351 cycling effect Effects 0.000 description 1
• WISCONQAEAWCKO-UHFFFAOYSA-N cyclohexa-2,4-diene-1-carboxylic acid Chemical compound OC(=O)C1CC=CC=C1 WISCONQAEAWCKO-UHFFFAOYSA-N 0.000 description 1
• 150000001945 cysteines Chemical class 0.000 description 1
• 230000001086 cytosolic effect Effects 0.000 description 1
• 230000007850 degeneration Effects 0.000 description 1
• 230000003111 delayed effect Effects 0.000 description 1
• 230000002939 deleterious effect Effects 0.000 description 1
• 210000004443 dendritic cell Anatomy 0.000 description 1
• OJSUWTDDXLCUFR-YVKIRAPASA-N deoxy-bigchap Chemical compound C([C@@H]1CC2)[C@@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@@H]([C@@H](CCC(=O)N(CCCNC(=O)[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO)CCCNC(=O)[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO)C)[C@@]2(C)[C@H](O)C1 OJSUWTDDXLCUFR-YVKIRAPASA-N 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
• 238000010511 deprotection reaction Methods 0.000 description 1
• 238000001212 derivatisation Methods 0.000 description 1
• 230000006866 deterioration Effects 0.000 description 1
• 208000022734 developmental defect during embryogenesis Diseases 0.000 description 1
• 238000010586 diagram Methods 0.000 description 1
• 238000000502 dialysis Methods 0.000 description 1
• 238000001085 differential centrifugation Methods 0.000 description 1
• 230000029087 digestion Effects 0.000 description 1
• 238000007865 diluting Methods 0.000 description 1
• PSLWZOIUBRXAQW-UHFFFAOYSA-M dimethyl(dioctadecyl)azanium;bromide Chemical compound [Br-].CCCCCCCCCCCCCCCCCC[N+](C)(C)CCCCCCCCCCCCCCCCCC PSLWZOIUBRXAQW-UHFFFAOYSA-M 0.000 description 1
• 229910001882 dioxygen Inorganic materials 0.000 description 1
• 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 1
• 239000002270 dispersing agent Substances 0.000 description 1
• NAGJZTKCGNOGPW-UHFFFAOYSA-N dithiophosphoric acid Chemical class OP(O)(S)=S NAGJZTKCGNOGPW-UHFFFAOYSA-N 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 241001493065 dsRNA viruses Species 0.000 description 1
• 229960001484 edetic acid Drugs 0.000 description 1
• 230000001516 effect on protein Effects 0.000 description 1
• 239000012636 effector Substances 0.000 description 1
• 238000002337 electrophoretic mobility shift assay Methods 0.000 description 1
• 238000004520 electroporation Methods 0.000 description 1
• 238000000132 electrospray ionisation Methods 0.000 description 1
• 239000003480 eluent Substances 0.000 description 1
• 238000005538 encapsulation Methods 0.000 description 1
• 230000012202 endocytosis Effects 0.000 description 1
• 210000002889 endothelial cell Anatomy 0.000 description 1
• 230000007071 enzymatic hydrolysis Effects 0.000 description 1
• 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
• 238000006911 enzymatic reaction Methods 0.000 description 1
• 230000003628 erosive effect Effects 0.000 description 1
• 230000032050 esterification Effects 0.000 description 1
• 238000005886 esterification reaction Methods 0.000 description 1
• 150000002148 esters Chemical class 0.000 description 1
• 229920001249 ethyl cellulose Polymers 0.000 description 1
• 235000019325 ethyl cellulose Nutrition 0.000 description 1
• 239000005038 ethylene vinyl acetate Substances 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 239000003925 fat Substances 0.000 description 1
• 239000012894 fetal calf serum Substances 0.000 description 1
• 210000003495 flagella Anatomy 0.000 description 1
• GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
• 239000007850 fluorescent dye Substances 0.000 description 1
• 238000001215 fluorescent labelling Methods 0.000 description 1
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
• 238000005194 fractionation Methods 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• 230000002538 fungal effect Effects 0.000 description 1
• 238000001502 gel electrophoresis Methods 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 238000002523 gelfiltration Methods 0.000 description 1
• 238000001476 gene delivery Methods 0.000 description 1
• 210000004602 germ cell Anatomy 0.000 description 1
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
• 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 1
• YPZRWBKMTBYPTK-BJDJZHNGSA-N glutathione disulfide Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@H](C(=O)NCC(O)=O)CSSC[C@@H](C(=O)NCC(O)=O)NC(=O)CC[C@H](N)C(O)=O YPZRWBKMTBYPTK-BJDJZHNGSA-N 0.000 description 1
• SYUXAJSOZXEFPP-UHFFFAOYSA-N glutin Natural products COc1c(O)cc2OC(=CC(=O)c2c1O)c3ccccc3OC4OC(CO)C(O)C(O)C4O SYUXAJSOZXEFPP-UHFFFAOYSA-N 0.000 description 1
• 150000004676 glycans Chemical class 0.000 description 1
• 150000002334 glycols Chemical class 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
• 125000000623 heterocyclic group Chemical group 0.000 description 1
• 238000004128 high performance liquid chromatography Methods 0.000 description 1
• 102000049489 human GALNS Human genes 0.000 description 1
• 210000003917 human chromosome Anatomy 0.000 description 1
• 150000007857 hydrazones Chemical class 0.000 description 1
• 125000001183 hydrocarbyl group Chemical group 0.000 description 1
• 230000002209 hydrophobic effect Effects 0.000 description 1
• 229920013821 hydroxy alkyl cellulose Polymers 0.000 description 1
• 229930005346 hydroxycinnamic acid Natural products 0.000 description 1
• 235000010359 hydroxycinnamic acids Nutrition 0.000 description 1
• 230000033444 hydroxylation Effects 0.000 description 1
• 238000005805 hydroxylation reaction Methods 0.000 description 1
• 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
• 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
• UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
• 230000008073 immune recognition Effects 0.000 description 1
• 238000002649 immunization Methods 0.000 description 1
• 230000003053 immunization Effects 0.000 description 1
• 238000003317 immunochromatography Methods 0.000 description 1
• 229940127121 immunoconjugate Drugs 0.000 description 1
• 102000018358 immunoglobulin Human genes 0.000 description 1
• 229940072221 immunoglobulins Drugs 0.000 description 1
• 238000003364 immunohistochemistry Methods 0.000 description 1
• 230000008676 import Effects 0.000 description 1
• 231100000986 in utero exposure Toxicity 0.000 description 1
• 230000002458 infectious effect Effects 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
• 229940102223 injectable solution Drugs 0.000 description 1
• 229940102213 injectable suspension Drugs 0.000 description 1
• 238000002743 insertional mutagenesis Methods 0.000 description 1
• 230000002452 interceptive effect Effects 0.000 description 1
• 210000002490 intestinal epithelial cell Anatomy 0.000 description 1
• 210000000936 intestine Anatomy 0.000 description 1
• 230000010189 intracellular transport Effects 0.000 description 1
• 238000004255 ion exchange chromatography Methods 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 229960000310 isoleucine Drugs 0.000 description 1
• AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
• QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
• 210000002510 keratinocyte Anatomy 0.000 description 1
• 238000002372 labelling Methods 0.000 description 1
• 239000004310 lactic acid Substances 0.000 description 1
• 235000014655 lactic acid Nutrition 0.000 description 1
• 150000002611 lead compounds Chemical class 0.000 description 1
• 210000000265 leukocyte Anatomy 0.000 description 1
• GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
• 108010052968 leupeptin Proteins 0.000 description 1
• 238000000670 ligand binding assay Methods 0.000 description 1
• 125000005647 linker group Chemical group 0.000 description 1
• 238000005567 liquid scintillation counting Methods 0.000 description 1
• 238000011068 loading method Methods 0.000 description 1
• 238000012153 long-term therapy Methods 0.000 description 1
• 239000007937 lozenge Substances 0.000 description 1
• 238000004020 luminiscence type Methods 0.000 description 1
• 210000004698 lymphocyte Anatomy 0.000 description 1
• 239000006166 lysate Substances 0.000 description 1
• 230000001320 lysogenic effect Effects 0.000 description 1
• 230000002132 lysosomal effect Effects 0.000 description 1
• 210000003712 lysosome Anatomy 0.000 description 1
• 230000001868 lysosomic effect Effects 0.000 description 1
• 230000002101 lytic effect Effects 0.000 description 1
• 238000012423 maintenance Methods 0.000 description 1
• 208000035853 malformation syndrome Diseases 0.000 description 1
• 210000005075 mammary gland Anatomy 0.000 description 1
• 238000013507 mapping Methods 0.000 description 1
• 238000001819 mass spectrum Methods 0.000 description 1
• 238000001254 matrix assisted laser desorption--ionisation time-of-flight mass spectrum Methods 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 239000002609 medium Substances 0.000 description 1
• 201000001441 melanoma Diseases 0.000 description 1
• 238000002844 melting Methods 0.000 description 1
• 230000008018 melting Effects 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• 230000004060 metabolic process Effects 0.000 description 1
• 230000003458 metachromatic effect Effects 0.000 description 1
• 229910021645 metal ion Inorganic materials 0.000 description 1
• 229910044991 metal oxide Inorganic materials 0.000 description 1
• 150000004706 metal oxides Chemical class 0.000 description 1
• 125000005395 methacrylic acid group Chemical group 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 235000010981 methylcellulose Nutrition 0.000 description 1
• 238000010208 microarray analysis Methods 0.000 description 1
• 239000011325 microbead Substances 0.000 description 1
• 238000000520 microinjection Methods 0.000 description 1
• 239000004005 microsphere Substances 0.000 description 1
• 206010027599 migraine Diseases 0.000 description 1
• 230000003278 mimic effect Effects 0.000 description 1
• 230000011278 mitosis Effects 0.000 description 1
• 230000000051 modifying effect Effects 0.000 description 1
• 208000012251 mucopolysaccharidosis Ih Diseases 0.000 description 1
• 210000000663 muscle cell Anatomy 0.000 description 1
• 238000002703 mutagenesis Methods 0.000 description 1
• 231100000350 mutagenesis Toxicity 0.000 description 1
• 210000005012 myelin Anatomy 0.000 description 1
• 210000004165 myocardium Anatomy 0.000 description 1
• ZIUHHBKFKCYYJD-UHFFFAOYSA-N n,n'-methylenebisacrylamide Chemical compound C=CC(=O)NCNC(=O)C=C ZIUHHBKFKCYYJD-UHFFFAOYSA-N 0.000 description 1
• ZLDPNFYTUDQDMJ-UHFFFAOYSA-N n-octadecyloctadecan-1-amine;hydrobromide Chemical compound Br.CCCCCCCCCCCCCCCCCCNCCCCCCCCCCCCCCCCCC ZLDPNFYTUDQDMJ-UHFFFAOYSA-N 0.000 description 1
• 210000004897 n-terminal region Anatomy 0.000 description 1
• 239000007922 nasal spray Substances 0.000 description 1
• 239000013642 negative control Substances 0.000 description 1
• 210000003061 neural cell Anatomy 0.000 description 1
• 210000004498 neuroglial cell Anatomy 0.000 description 1
• 229910000480 nickel oxide Inorganic materials 0.000 description 1
• 238000003199 nucleic acid amplification method Methods 0.000 description 1
• 238000003499 nucleic acid array Methods 0.000 description 1
• 210000004940 nucleus Anatomy 0.000 description 1
• 229920001778 nylon Polymers 0.000 description 1
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
• 239000002751 oligonucleotide probe Substances 0.000 description 1
• 238000010397 one-hybrid screening Methods 0.000 description 1
• 238000005457 optimization Methods 0.000 description 1
• 125000000962 organic group Chemical group 0.000 description 1
• 230000008520 organization Effects 0.000 description 1
• 210000001672 ovary Anatomy 0.000 description 1
• YPZRWBKMTBYPTK-UHFFFAOYSA-N oxidized gamma-L-glutamyl-L-cysteinylglycine Natural products OC(=O)C(N)CCC(=O)NC(C(=O)NCC(O)=O)CSSCC(C(=O)NCC(O)=O)NC(=O)CCC(N)C(O)=O YPZRWBKMTBYPTK-UHFFFAOYSA-N 0.000 description 1
• GNRSAWUEBMWBQH-UHFFFAOYSA-N oxonickel Chemical compound [Ni]=O GNRSAWUEBMWBQH-UHFFFAOYSA-N 0.000 description 1
• 229910052760 oxygen Inorganic materials 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 239000008188 pellet Substances 0.000 description 1
• 108010091212 pepstatin Proteins 0.000 description 1
• FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
• 102000023856 peptide binding proteins Human genes 0.000 description 1
• 108091008399 peptide binding proteins Proteins 0.000 description 1
• 238000010647 peptide synthesis reaction Methods 0.000 description 1
• YEHCICAEULNIGD-MZMPZRCHSA-N pergolide Chemical compound C1=CC([C@H]2C[C@@H](CSC)CN([C@@H]2C2)CCC)=C3C2=CNC3=C1 YEHCICAEULNIGD-MZMPZRCHSA-N 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
• 210000001428 peripheral nervous system Anatomy 0.000 description 1
• 239000012466 permeate Substances 0.000 description 1
• 108040007629 peroxidase activity proteins Proteins 0.000 description 1
• 238000011170 pharmaceutical development Methods 0.000 description 1
• 239000000546 pharmaceutical excipient Substances 0.000 description 1
• 239000002831 pharmacologic agent Substances 0.000 description 1
• 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• 239000002953 phosphate buffered saline Substances 0.000 description 1
• 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
• 150000008298 phosphoramidates Chemical class 0.000 description 1
• 150000003014 phosphoric acid esters Chemical class 0.000 description 1
• 230000026731 phosphorylation Effects 0.000 description 1
• 238000006366 phosphorylation reaction Methods 0.000 description 1
• 102000020233 phosphotransferase Human genes 0.000 description 1
• 210000003635 pituitary gland Anatomy 0.000 description 1
• 210000002826 placenta Anatomy 0.000 description 1
• 229920000233 poly(alkylene oxides) Polymers 0.000 description 1
• 229920001483 poly(ethyl methacrylate) polymer Polymers 0.000 description 1
• 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
• 229920000205 poly(isobutyl methacrylate) Polymers 0.000 description 1
• 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
• 239000004584 polyacrylic acid Substances 0.000 description 1
• 229920001515 polyalkylene glycol Polymers 0.000 description 1
• 229920001610 polycaprolactone Polymers 0.000 description 1
• 229920000515 polycarbonate Polymers 0.000 description 1
• 229920006149 polyester-amide block copolymer Polymers 0.000 description 1
• 229920000573 polyethylene Polymers 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 229920000139 polyethylene terephthalate Polymers 0.000 description 1
• 239000005020 polyethylene terephthalate Substances 0.000 description 1
• 229920000656 polylysine Polymers 0.000 description 1
• 239000004926 polymethyl methacrylate Substances 0.000 description 1
• 102000054765 polymorphisms of proteins Human genes 0.000 description 1
• 229920001155 polypropylene Polymers 0.000 description 1
• 229920001282 polysaccharide Polymers 0.000 description 1
• 239000005017 polysaccharide Substances 0.000 description 1
• 229920001296 polysiloxane Polymers 0.000 description 1
• 229920002689 polyvinyl acetate Polymers 0.000 description 1
• 239000011118 polyvinyl acetate Substances 0.000 description 1
• 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
• 229920000915 polyvinyl chloride Polymers 0.000 description 1
• 239000004800 polyvinyl chloride Substances 0.000 description 1
• 229920001290 polyvinyl ester Polymers 0.000 description 1
• 229920001289 polyvinyl ether Polymers 0.000 description 1
• 235000011056 potassium acetate Nutrition 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 239000000843 powder Substances 0.000 description 1
• 239000002244 precipitate Substances 0.000 description 1
• 238000001556 precipitation Methods 0.000 description 1
• 230000035935 pregnancy Effects 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 230000001566 pro-viral effect Effects 0.000 description 1
• 238000004393 prognosis Methods 0.000 description 1
• 210000002307 prostate Anatomy 0.000 description 1
• 108020001580 protein domains Proteins 0.000 description 1
• 238000001243 protein synthesis Methods 0.000 description 1
• 230000002685 pulmonary effect Effects 0.000 description 1
• 238000003906 pulsed field gel electrophoresis Methods 0.000 description 1
• 150000003212 purines Chemical class 0.000 description 1
• 229950010131 puromycin Drugs 0.000 description 1
• 150000003230 pyrimidines Chemical class 0.000 description 1
• 238000002708 random mutagenesis Methods 0.000 description 1
• 230000006798 recombination Effects 0.000 description 1
• 238000005215 recombination Methods 0.000 description 1
• 230000009467 reduction Effects 0.000 description 1
• 230000011514 reflex Effects 0.000 description 1
• 230000008929 regeneration Effects 0.000 description 1
• 238000011069 regeneration method Methods 0.000 description 1
• 229920005989 resin Polymers 0.000 description 1
• 239000011347 resin Substances 0.000 description 1
• 230000000717 retained effect Effects 0.000 description 1
• 210000001995 reticulocyte Anatomy 0.000 description 1
• 238000010839 reverse transcription Methods 0.000 description 1
• 239000002336 ribonucleotide Substances 0.000 description 1
• 125000002652 ribonucleotide group Chemical group 0.000 description 1
• 108091092562 ribozyme Proteins 0.000 description 1
• 102200063016 rs2819590 Human genes 0.000 description 1
• 102220095028 rs876659729 Human genes 0.000 description 1
• 239000010979 ruby Substances 0.000 description 1
• 229910001750 ruby Inorganic materials 0.000 description 1
• 210000003296 saliva Anatomy 0.000 description 1
• 210000003079 salivary gland Anatomy 0.000 description 1
• 235000019515 salmon Nutrition 0.000 description 1
• 238000007423 screening assay Methods 0.000 description 1
• 238000010845 search algorithm Methods 0.000 description 1
• 230000035945 sensitivity Effects 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• 238000007493 shaping process Methods 0.000 description 1
• FZHAPNGMFPVSLP-UHFFFAOYSA-N silanamine Chemical class [SiH3]N FZHAPNGMFPVSLP-UHFFFAOYSA-N 0.000 description 1
• 150000004756 silanes Chemical class 0.000 description 1
• 239000000377 silicon dioxide Substances 0.000 description 1
• 238000001542 size-exclusion chromatography Methods 0.000 description 1
• 210000002027 skeletal muscle Anatomy 0.000 description 1
• 208000017520 skin disease Diseases 0.000 description 1
• 238000003307 slaughter Methods 0.000 description 1
• 239000001509 sodium citrate Substances 0.000 description 1
• NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
• 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
• 238000009987 spinning Methods 0.000 description 1
• 210000000952 spleen Anatomy 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 230000010473 stable expression Effects 0.000 description 1
• 238000010186 staining Methods 0.000 description 1
• 229910001220 stainless steel Inorganic materials 0.000 description 1
• 239000010935 stainless steel Substances 0.000 description 1
• 238000012289 standard assay Methods 0.000 description 1
• 239000010421 standard material Substances 0.000 description 1
• 210000000130 stem cell Anatomy 0.000 description 1
• 239000011550 stock solution Substances 0.000 description 1
• 210000002784 stomach Anatomy 0.000 description 1
• 238000003860 storage Methods 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 230000002195 synergetic effect Effects 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 230000009885 systemic effect Effects 0.000 description 1
• 238000012353 t test Methods 0.000 description 1
• 238000004885 tandem mass spectrometry Methods 0.000 description 1
• 238000010846 tandem mass spectrometry analysis Methods 0.000 description 1
• 230000002123 temporal effect Effects 0.000 description 1
• 150000003505 terpenes Chemical class 0.000 description 1
• WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
• 229940124597 therapeutic agent Drugs 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
• 125000004055 thiomethyl group Chemical group [H]SC([H])([H])* 0.000 description 1
• 210000001541 thymus gland Anatomy 0.000 description 1
• 210000001685 thyroid gland Anatomy 0.000 description 1
• 239000003104 tissue culture media Substances 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 210000003437 trachea Anatomy 0.000 description 1
• NGSWKAQJJWESNS-ZZXKWVIFSA-N trans-4-coumaric acid Chemical compound OC(=O)\C=C\C1=CC=C(O)C=C1 NGSWKAQJJWESNS-ZZXKWVIFSA-N 0.000 description 1
• 230000005026 transcription initiation Effects 0.000 description 1
• 230000002103 transcriptional effect Effects 0.000 description 1
• 239000012096 transfection reagent Substances 0.000 description 1
• 230000010474 transient expression Effects 0.000 description 1
• 230000014621 translational initiation Effects 0.000 description 1
• 238000011269 treatment regimen Methods 0.000 description 1
• 150000003626 triacylglycerols Chemical class 0.000 description 1
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
• 229950009811 ubenimex Drugs 0.000 description 1
• 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
• 230000009452 underexpressoin Effects 0.000 description 1
• 241000701447 unidentified baculovirus Species 0.000 description 1
• 210000003932 urinary bladder Anatomy 0.000 description 1
• 210000004291 uterus Anatomy 0.000 description 1
• 239000004474 valine Substances 0.000 description 1
• 210000005167 vascular cell Anatomy 0.000 description 1
• 230000009385 viral infection Effects 0.000 description 1
• 210000002845 virion Anatomy 0.000 description 1
• 208000012500 vitamin K-antagonist embryofetopathy Diseases 0.000 description 1
• 108010047303 von Willebrand Factor Proteins 0.000 description 1
• PJVWKTKQMONHTI-UHFFFAOYSA-N warfarin Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 PJVWKTKQMONHTI-UHFFFAOYSA-N 0.000 description 1
• 229960005080 warfarin Drugs 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 238000001086 yeast two-hybrid system Methods 0.000 description 1
• 239000005019 zein Substances 0.000 description 1
• 229940093612 zein Drugs 0.000 description 1
• DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1