BR112021013941A2 - Polinucleotídeo recombinante, vetor viral, método para obter um vetor viral recombinante, método para fornecer proteína enpp1 ou enpp3 a um mamífero, composição farmacêutica, método para evitar ou reduzir a progressão de uma doença em um mamífero em necessidade do mesmo, célula, método para tratar ou evitar uma doença ou distúrbio de calcificação patológica ou ossificação patológica em um indivíduo em necessidade do mesmo, método para tratar um indivíduo com deficiência de proteína enpp1, método para produzir um vetor viral recombinante e vetor viral recombinante - Google Patents

Info

Publication number

BR112021013941A2

BR112021013941A2 BR112021013941-9A BR112021013941A BR112021013941A2 BR 112021013941 A2 BR112021013941 A2 BR 112021013941A2 BR 112021013941 A BR112021013941 A BR 112021013941A BR 112021013941 A2 BR112021013941 A2 BR 112021013941A2

Authority

BR

Brazil

Prior art keywords

enpp1

viral vector

enpp3

signal peptide

vector

Prior art date

2019-01-18

Links

• Espacenet
• Global Dossier
• Discuss

• 239000013603 viral vector Substances 0.000 title claims abstract description 279
• 238000000034 method Methods 0.000 title claims abstract description 187
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 122
• 102000040430 polynucleotide Human genes 0.000 title claims abstract description 104
• 108091033319 polynucleotide Proteins 0.000 title claims abstract description 104
• 239000002157 polynucleotide Substances 0.000 title claims abstract description 104
• 230000002308 calcification Effects 0.000 title claims abstract description 77
• 201000010099 disease Diseases 0.000 title claims abstract description 73
• 241000124008 Mammalia Species 0.000 title claims abstract description 59
• 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 55
• 208000035475 disorder Diseases 0.000 title claims abstract description 46
• 230000001575 pathological effect Effects 0.000 title claims abstract description 26
• 208000034970 Heterotopic Ossification Diseases 0.000 title claims abstract description 12
• 208000008425 Protein deficiency Diseases 0.000 title claims abstract description 12
• 101000812677 Homo sapiens Nucleotide pyrophosphatase Proteins 0.000 title claims description 254
• 102100039306 Nucleotide pyrophosphatase Human genes 0.000 title claims description 254
• 101000897042 Homo sapiens Nucleotide pyrophosphatase Proteins 0.000 title claims description 196
• 102100021969 Nucleotide pyrophosphatase Human genes 0.000 title claims description 185
• 239000013598 vector Substances 0.000 claims abstract description 169
• 230000011164 ossification Effects 0.000 claims abstract description 23
• 101000995829 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) Nucleotide pyrophosphatase Proteins 0.000 claims description 251
• 210000004027 cell Anatomy 0.000 claims description 178
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 137
• 229920001184 polypeptide Polymers 0.000 claims description 132
• 102000004196 processed proteins & peptides Human genes 0.000 claims description 132
• 108010076504 Protein Sorting Signals Proteins 0.000 claims description 125
• 230000014509 gene expression Effects 0.000 claims description 82
• 208000004434 Calcinosis Diseases 0.000 claims description 76
• XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 claims description 73
• 208000020832 chronic kidney disease Diseases 0.000 claims description 68
• 101710154607 Azurocidin Proteins 0.000 claims description 61
• 239000013607 AAV vector Substances 0.000 claims description 50
• 239000002773 nucleotide Substances 0.000 claims description 47
• 150000007523 nucleic acids Chemical group 0.000 claims description 46
• 241000282414 Homo sapiens Species 0.000 claims description 45
• 208000005475 Vascular calcification Diseases 0.000 claims description 40
• 239000013612 plasmid Substances 0.000 claims description 39
• 230000004927 fusion Effects 0.000 claims description 38
• 238000011282 treatment Methods 0.000 claims description 38
• 101150011046 NPP1 gene Proteins 0.000 claims description 37
• 125000003729 nucleotide group Chemical group 0.000 claims description 35
• 239000000203 mixture Substances 0.000 claims description 34
• 102100028187 ATP-binding cassette sub-family C member 6 Human genes 0.000 claims description 30
• 208000033173 Generalized arterial calcification of infancy Diseases 0.000 claims description 28
• 208000004900 arterial calcification of infancy Diseases 0.000 claims description 28
• 210000004185 liver Anatomy 0.000 claims description 28
• 102000009027 Albumins Human genes 0.000 claims description 26
• 108010088751 Albumins Proteins 0.000 claims description 26
• 241000700605 Viruses Species 0.000 claims description 25
• 108091028043 Nucleic acid sequence Proteins 0.000 claims description 24
• 235000011180 diphosphates Nutrition 0.000 claims description 23
• 229910052500 inorganic mineral Inorganic materials 0.000 claims description 23
• 239000011707 mineral Substances 0.000 claims description 23
• 241000702423 Adeno-associated virus - 2 Species 0.000 claims description 18
• 208000005050 Familial Hypophosphatemic Rickets Diseases 0.000 claims description 18
• 201000006035 X-linked dominant hypophosphatemic rickets Diseases 0.000 claims description 17
• 230000008488 polyadenylation Effects 0.000 claims description 17
• 210000004872 soft tissue Anatomy 0.000 claims description 17
• 241001634120 Adeno-associated virus - 5 Species 0.000 claims description 14
• 208000031878 X-linked hypophosphatemia Diseases 0.000 claims description 14
• 239000003937 drug carrier Substances 0.000 claims description 14
• 239000012634 fragment Substances 0.000 claims description 14
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
• 108010067390 Viral Proteins Proteins 0.000 claims description 13
• 210000004962 mammalian cell Anatomy 0.000 claims description 13
• 238000004806 packaging method and process Methods 0.000 claims description 13
• 230000003197 catalytic effect Effects 0.000 claims description 11
• 108020001507 fusion proteins Proteins 0.000 claims description 11
• 102000037865 fusion proteins Human genes 0.000 claims description 11
• 230000004777 loss-of-function mutation Effects 0.000 claims description 11
• 239000002243 precursor Substances 0.000 claims description 11
• 230000002037 soft tissue calcification Effects 0.000 claims description 11
• 241001655883 Adeno-associated virus - 1 Species 0.000 claims description 10
• 241000972680 Adeno-associated virus - 6 Species 0.000 claims description 10
• CGVWDTRDPLOMHZ-FXQIFTODSA-N Gln-Glu-Asp Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O CGVWDTRDPLOMHZ-FXQIFTODSA-N 0.000 claims description 10
• 208000009889 Herpes Simplex Diseases 0.000 claims description 10
• 231100000673 dose–response relationship Toxicity 0.000 claims description 10
• 102100036093 Ectonucleotide pyrophosphatase/phosphodiesterase family member 7 Human genes 0.000 claims description 9
• 101000876377 Homo sapiens Ectonucleotide pyrophosphatase/phosphodiesterase family member 7 Proteins 0.000 claims description 9
• 101710163270 Nuclease Proteins 0.000 claims description 9
• 210000004446 longitudinal ligament Anatomy 0.000 claims description 9
• 238000005259 measurement Methods 0.000 claims description 9
• 208000020084 Bone disease Diseases 0.000 claims description 8
• 101000986621 Homo sapiens ATP-binding cassette sub-family C member 6 Proteins 0.000 claims description 8
• 241000283984 Rodentia Species 0.000 claims description 8
• 108010050122 alpha 1-Antitrypsin Proteins 0.000 claims description 8
• 102000015395 alpha 1-Antitrypsin Human genes 0.000 claims description 8
• 229940024142 alpha 1-antitrypsin Drugs 0.000 claims description 8
• 230000002829 reductive effect Effects 0.000 claims description 8
• 102000008100 Human Serum Albumin Human genes 0.000 claims description 7
• 108091006905 Human Serum Albumin Proteins 0.000 claims description 7
• 101150071357 NPP2 gene Proteins 0.000 claims description 7
• 101100080097 Phytophthora capsici NLP2 gene Proteins 0.000 claims description 7
• 238000001514 detection method Methods 0.000 claims description 7
• 230000002255 enzymatic effect Effects 0.000 claims description 7
• 229930029653 phosphoenolpyruvate Natural products 0.000 claims description 7
• DTBNBXWJWCWCIK-UHFFFAOYSA-N phosphoenolpyruvic acid Chemical compound OC(=O)C(=C)OP(O)(O)=O DTBNBXWJWCWCIK-UHFFFAOYSA-N 0.000 claims description 7
• 101150095012 ABCC6 gene Proteins 0.000 claims description 6
• 241000238631 Hexapoda Species 0.000 claims description 6
• 239000012472 biological sample Substances 0.000 claims description 6
• 210000005260 human cell Anatomy 0.000 claims description 6
• 230000036470 plasma concentration Effects 0.000 claims description 6
• CZCCVJUUWBMISW-FXQIFTODSA-N Pro-Ser-Cys Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O CZCCVJUUWBMISW-FXQIFTODSA-N 0.000 claims description 5
• NHQVWACSJZJCGJ-FLBSBUHZSA-N Thr-Thr-Ile Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O NHQVWACSJZJCGJ-FLBSBUHZSA-N 0.000 claims description 4
• LZEUDRYSAZAJIO-AUTRQRHGSA-N Glu-Val-Glu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O LZEUDRYSAZAJIO-AUTRQRHGSA-N 0.000 claims description 3
• WNGHUXFWEWTKAO-YUMQZZPRSA-N Gly-Ser-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)CN WNGHUXFWEWTKAO-YUMQZZPRSA-N 0.000 claims description 3
• WIDZHJTYKYBLSR-DCAQKATOSA-N Leu-Glu-Glu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O WIDZHJTYKYBLSR-DCAQKATOSA-N 0.000 claims description 3
• SZTTYWIUCGSURQ-AUTRQRHGSA-N Val-Glu-Glu Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O SZTTYWIUCGSURQ-AUTRQRHGSA-N 0.000 claims description 3
• 239000003446 ligand Substances 0.000 claims description 3
• LLZXNUUIBOALNY-QWRGUYRKSA-N Gly-Leu-Lys Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CCCCN LLZXNUUIBOALNY-QWRGUYRKSA-N 0.000 claims description 2
• GMWNQSGWWGKTSF-LFSVMHDDSA-N Phe-Thr-Ala Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(O)=O GMWNQSGWWGKTSF-LFSVMHDDSA-N 0.000 claims description 2
• 102000043635 human AZU1 Human genes 0.000 claims 18
• 241000202702 Adeno-associated virus - 3 Species 0.000 claims 3
• 241000580270 Adeno-associated virus - 4 Species 0.000 claims 3
• 241001164823 Adeno-associated virus - 7 Species 0.000 claims 3
• 241001164825 Adeno-associated virus - 8 Species 0.000 claims 3
• 125000003275 alpha amino acid group Chemical group 0.000 claims 3
• 108090000623 proteins and genes Proteins 0.000 abstract description 166
• 102000004169 proteins and genes Human genes 0.000 abstract description 102
• 238000001727 in vivo Methods 0.000 abstract description 5
• 241000699670 Mus sp. Species 0.000 description 99
• 235000018102 proteins Nutrition 0.000 description 98
• 210000001519 tissue Anatomy 0.000 description 47
• 239000002245 particle Substances 0.000 description 46
• 230000003612 virological effect Effects 0.000 description 45
• 102100030009 Azurocidin Human genes 0.000 description 44
• 210000004369 blood Anatomy 0.000 description 34
• 239000008280 blood Substances 0.000 description 34
• 101150017770 ENPP1 gene Proteins 0.000 description 32
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 32
• 238000002347 injection Methods 0.000 description 32
• 239000007924 injection Substances 0.000 description 32
• 210000000988 bone and bone Anatomy 0.000 description 30
• 230000006870 function Effects 0.000 description 29
• 208000024891 symptom Diseases 0.000 description 29
• 241001465754 Metazoa Species 0.000 description 28
• 210000002381 plasma Anatomy 0.000 description 28
• 101100080092 Phytophthora capsici NLP1 gene Proteins 0.000 description 26
• 230000009467 reduction Effects 0.000 description 26
• 210000002966 serum Anatomy 0.000 description 26
• 102000039446 nucleic acids Human genes 0.000 description 25
• 108020004707 nucleic acids Proteins 0.000 description 25
• 108020004414 DNA Proteins 0.000 description 23
• 238000010172 mouse model Methods 0.000 description 23
• ZKHQWZAMYRWXGA-KQYNXXCUSA-N Adenosine triphosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-N 0.000 description 22
• 108090000569 Fibroblast Growth Factor-23 Proteins 0.000 description 22
• 201000004613 Pseudoxanthoma elasticum Diseases 0.000 description 22
• 230000001965 increasing effect Effects 0.000 description 22
• 208000023558 pseudoxanthoma elasticum (inherited or acquired) Diseases 0.000 description 22
• 239000000758 substrate Substances 0.000 description 22
• 239000003623 enhancer Substances 0.000 description 21
• 235000010755 mineral Nutrition 0.000 description 21
• 230000000694 effects Effects 0.000 description 20
• 238000004519 manufacturing process Methods 0.000 description 20
• 239000000047 product Substances 0.000 description 20
• 230000010076 replication Effects 0.000 description 20
• 102000004042 Fibroblast Growth Factor-23 Human genes 0.000 description 19
• 235000005911 diet Nutrition 0.000 description 19
• 230000001105 regulatory effect Effects 0.000 description 19
• 230000001225 therapeutic effect Effects 0.000 description 19
• 230000037213 diet Effects 0.000 description 18
• 210000002700 urine Anatomy 0.000 description 18
• 241000699666 Mus <mouse, genus> Species 0.000 description 17
• 102000003982 Parathyroid hormone Human genes 0.000 description 17
• 108090000445 Parathyroid hormone Proteins 0.000 description 17
• 108010067341 ectonucleotide pyrophosphatase phosphodiesterase 1 Proteins 0.000 description 17
• 239000000199 parathyroid hormone Substances 0.000 description 17
• 229960001319 parathyroid hormone Drugs 0.000 description 17
• 239000004202 carbamide Substances 0.000 description 16
• 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 16
• 239000002953 phosphate buffered saline Substances 0.000 description 16
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 15
• 241000702421 Dependoparvovirus Species 0.000 description 15
• 210000001367 artery Anatomy 0.000 description 15
• 230000027455 binding Effects 0.000 description 15
• 239000011575 calcium Substances 0.000 description 15
• 229910052791 calcium Inorganic materials 0.000 description 15
• 230000002103 transcriptional effect Effects 0.000 description 15
• 239000011710 vitamin D Substances 0.000 description 15
• 229940046008 vitamin d Drugs 0.000 description 15
• 229910019142 PO4 Inorganic materials 0.000 description 14
• 210000000234 capsid Anatomy 0.000 description 14
• 238000002591 computed tomography Methods 0.000 description 14
• CVSVTCORWBXHQV-UHFFFAOYSA-N creatine Chemical compound NC(=[NH2+])N(C)CC([O-])=O CVSVTCORWBXHQV-UHFFFAOYSA-N 0.000 description 14
• DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 14
• 208000002267 Anti-neutrophil cytoplasmic antibody-associated vasculitis Diseases 0.000 description 13
• 238000001415 gene therapy Methods 0.000 description 13
• 210000002216 heart Anatomy 0.000 description 13
• 210000003734 kidney Anatomy 0.000 description 13
• 235000021317 phosphate Nutrition 0.000 description 13
• 239000010452 phosphate Substances 0.000 description 13
• 238000012360 testing method Methods 0.000 description 13
• 241000701161 unidentified adenovirus Species 0.000 description 13
• 229930003316 Vitamin D Natural products 0.000 description 12
• QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 12
• 201000000523 end stage renal failure Diseases 0.000 description 12
• 208000015181 infectious disease Diseases 0.000 description 12
• 230000000670 limiting effect Effects 0.000 description 12
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 12
• 235000019166 vitamin D Nutrition 0.000 description 12
• 150000003710 vitamin D derivatives Chemical class 0.000 description 12
• 102000053602 DNA Human genes 0.000 description 11
• 108700019146 Transgenes Proteins 0.000 description 11
• 238000009472 formulation Methods 0.000 description 11
• 102000048180 human ENPP3 Human genes 0.000 description 11
• 238000013518 transcription Methods 0.000 description 11
• 230000035897 transcription Effects 0.000 description 11
• 102000009609 Pyrophosphatases Human genes 0.000 description 10
• 108010009413 Pyrophosphatases Proteins 0.000 description 10
• 238000009825 accumulation Methods 0.000 description 10
• 150000001413 amino acids Chemical group 0.000 description 10
• 230000033558 biomineral tissue development Effects 0.000 description 10
• 210000004351 coronary vessel Anatomy 0.000 description 10
• 230000002950 deficient Effects 0.000 description 10
• 208000028208 end stage renal disease Diseases 0.000 description 10
• 230000001939 inductive effect Effects 0.000 description 10
• 230000035772 mutation Effects 0.000 description 10
• 210000000056 organ Anatomy 0.000 description 10
• 210000003491 skin Anatomy 0.000 description 10
• 239000000243 solution Substances 0.000 description 10
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
• 241000714474 Rous sarcoma virus Species 0.000 description 9
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
• 230000015572 biosynthetic process Effects 0.000 description 9
• 238000003776 cleavage reaction Methods 0.000 description 9
• 238000002474 experimental method Methods 0.000 description 9
• -1 nucleotide triphosphates Chemical class 0.000 description 9
• 229910052698 phosphorus Inorganic materials 0.000 description 9
• 230000007017 scission Effects 0.000 description 9
• 210000002845 virion Anatomy 0.000 description 9
• 206010020772 Hypertension Diseases 0.000 description 8
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 8
• 239000002671 adjuvant Substances 0.000 description 8
• 238000004458 analytical method Methods 0.000 description 8
• 210000004204 blood vessel Anatomy 0.000 description 8
• 238000006243 chemical reaction Methods 0.000 description 8
• 230000003247 decreasing effect Effects 0.000 description 8
• 230000001419 dependent effect Effects 0.000 description 8
• 238000003384 imaging method Methods 0.000 description 8
• 230000007774 longterm Effects 0.000 description 8
• 239000000463 material Substances 0.000 description 8
• 238000010603 microCT Methods 0.000 description 8
• 208000005368 osteomalacia Diseases 0.000 description 8
• 239000011574 phosphorus Substances 0.000 description 8
• 230000004044 response Effects 0.000 description 8
• 229930024421 Adenine Natural products 0.000 description 7
• GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 7
• 102100023321 Ceruloplasmin Human genes 0.000 description 7
• 241000701022 Cytomegalovirus Species 0.000 description 7
• 101001117086 Dictyostelium discoideum cAMP/cGMP-dependent 3',5'-cAMP/cGMP phosphodiesterase A Proteins 0.000 description 7
• 229960000643 adenine Drugs 0.000 description 7
• 239000000427 antigen Substances 0.000 description 7
• 108091007433 antigens Proteins 0.000 description 7
• 102000036639 antigens Human genes 0.000 description 7
• 210000000709 aorta Anatomy 0.000 description 7
• 230000037396 body weight Effects 0.000 description 7
• AIYUHDOJVYHVIT-UHFFFAOYSA-M caesium chloride Chemical compound [Cl-].[Cs+] AIYUHDOJVYHVIT-UHFFFAOYSA-M 0.000 description 7
• 150000001875 compounds Chemical class 0.000 description 7
• 230000000875 corresponding effect Effects 0.000 description 7
• 229960003624 creatine Drugs 0.000 description 7
• 239000006046 creatine Substances 0.000 description 7
• 229940109239 creatinine Drugs 0.000 description 7
• 239000003814 drug Substances 0.000 description 7
• 230000007062 hydrolysis Effects 0.000 description 7
• 238000006460 hydrolysis reaction Methods 0.000 description 7
• 239000003018 immunosuppressive agent Substances 0.000 description 7
• 239000002609 medium Substances 0.000 description 7
• 230000008569 process Effects 0.000 description 7
• 238000000746 purification Methods 0.000 description 7
• 208000007442 rickets Diseases 0.000 description 7
• 210000000689 upper leg Anatomy 0.000 description 7
• 230000002485 urinary effect Effects 0.000 description 7
• 241000710929 Alphavirus Species 0.000 description 6
• 206010006002 Bone pain Diseases 0.000 description 6
• 108090000565 Capsid Proteins Proteins 0.000 description 6
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 6
• 102000004190 Enzymes Human genes 0.000 description 6
• 108090000790 Enzymes Proteins 0.000 description 6
• 208000029725 Metabolic bone disease Diseases 0.000 description 6
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
• 206010049088 Osteopenia Diseases 0.000 description 6
• 208000002193 Pain Diseases 0.000 description 6
• 241000710960 Sindbis virus Species 0.000 description 6
• 230000002159 abnormal effect Effects 0.000 description 6
• 230000005856 abnormality Effects 0.000 description 6
• UDMBCSSLTHHNCD-KQYNXXCUSA-N adenosine 5'-monophosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O UDMBCSSLTHHNCD-KQYNXXCUSA-N 0.000 description 6
• 210000002808 connective tissue Anatomy 0.000 description 6
• 238000000151 deposition Methods 0.000 description 6
• 238000011161 development Methods 0.000 description 6
• 230000018109 developmental process Effects 0.000 description 6
• 210000004177 elastic tissue Anatomy 0.000 description 6
• 229940088598 enzyme Drugs 0.000 description 6
• 239000013604 expression vector Substances 0.000 description 6
• 210000003128 head Anatomy 0.000 description 6
• 238000004128 high performance liquid chromatography Methods 0.000 description 6
• 238000001990 intravenous administration Methods 0.000 description 6
• 230000003907 kidney function Effects 0.000 description 6
• 208000010125 myocardial infarction Diseases 0.000 description 6
• 230000036407 pain Effects 0.000 description 6
• 230000002265 prevention Effects 0.000 description 6
• 239000011780 sodium chloride Substances 0.000 description 6
• 238000001890 transfection Methods 0.000 description 6
• 230000014616 translation Effects 0.000 description 6
• 210000003462 vein Anatomy 0.000 description 6
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 5
• 241000283690 Bos taurus Species 0.000 description 5
• UDMBCSSLTHHNCD-UHFFFAOYSA-N Coenzym Q(11) Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(O)=O)C(O)C1O UDMBCSSLTHHNCD-UHFFFAOYSA-N 0.000 description 5
• 241000701024 Human betaherpesvirus 5 Species 0.000 description 5
• 208000029663 Hypophosphatemia Diseases 0.000 description 5
• 101150045819 NPP3 gene Proteins 0.000 description 5
• 108700026244 Open Reading Frames Proteins 0.000 description 5
• 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 5
• 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 5
• PNNCWTXUWKENPE-UHFFFAOYSA-N [N].NC(N)=O Chemical compound [N].NC(N)=O PNNCWTXUWKENPE-UHFFFAOYSA-N 0.000 description 5
• LNQVTSROQXJCDD-UHFFFAOYSA-N adenosine monophosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(CO)C(OP(O)(O)=O)C1O LNQVTSROQXJCDD-UHFFFAOYSA-N 0.000 description 5
• 238000003556 assay Methods 0.000 description 5
• 230000004071 biological effect Effects 0.000 description 5
• 230000008468 bone growth Effects 0.000 description 5
• 239000001506 calcium phosphate Substances 0.000 description 5
• 229910000389 calcium phosphate Inorganic materials 0.000 description 5
• 235000011010 calcium phosphates Nutrition 0.000 description 5
• 230000000747 cardiac effect Effects 0.000 description 5
• 230000000295 complement effect Effects 0.000 description 5
• 230000007423 decrease Effects 0.000 description 5
• 230000007812 deficiency Effects 0.000 description 5
• 238000012217 deletion Methods 0.000 description 5
• 230000037430 deletion Effects 0.000 description 5
• 230000008021 deposition Effects 0.000 description 5
• 210000001508 eye Anatomy 0.000 description 5
• 230000036541 health Effects 0.000 description 5
• 230000028993 immune response Effects 0.000 description 5
• 210000000987 immune system Anatomy 0.000 description 5
• 229940124589 immunosuppressive drug Drugs 0.000 description 5
• 238000003780 insertion Methods 0.000 description 5
• 230000037431 insertion Effects 0.000 description 5
• 238000010606 normalization Methods 0.000 description 5
• 230000002085 persistent effect Effects 0.000 description 5
• 102000005962 receptors Human genes 0.000 description 5
• 108020003175 receptors Proteins 0.000 description 5
• 238000002603 single-photon emission computed tomography Methods 0.000 description 5
• 235000000346 sugar Nutrition 0.000 description 5
• 230000004083 survival effect Effects 0.000 description 5
• 230000008719 thickening Effects 0.000 description 5
• 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 5
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
• 230000004584 weight gain Effects 0.000 description 5
• 235000019786 weight gain Nutrition 0.000 description 5
• 101100524319 Adeno-associated virus 2 (isolate Srivastava/1982) Rep52 gene Proteins 0.000 description 4
• 101100524324 Adeno-associated virus 2 (isolate Srivastava/1982) Rep78 gene Proteins 0.000 description 4
• 206010051714 Calciphylaxis Diseases 0.000 description 4
• 108091026890 Coding region Proteins 0.000 description 4
• PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 4
• 230000004543 DNA replication Effects 0.000 description 4
• 206010013975 Dyspnoeas Diseases 0.000 description 4
• WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 4
• 206010019280 Heart failures Diseases 0.000 description 4
• 241000725303 Human immunodeficiency virus Species 0.000 description 4
• 102100021244 Integral membrane protein GPR180 Human genes 0.000 description 4
• 208000000913 Kidney Calculi Diseases 0.000 description 4
• 241000713666 Lentivirus Species 0.000 description 4
• TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
• 206010029148 Nephrolithiasis Diseases 0.000 description 4
• 241000700159 Rattus Species 0.000 description 4
• 229910052770 Uranium Inorganic materials 0.000 description 4
• DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 4
• 108020005202 Viral DNA Proteins 0.000 description 4
• 238000010171 animal model Methods 0.000 description 4
• 201000003674 autosomal dominant hypophosphatemic rickets Diseases 0.000 description 4
• 239000013592 cell lysate Substances 0.000 description 4
• 229960004397 cyclophosphamide Drugs 0.000 description 4
• 229940079593 drug Drugs 0.000 description 4
• 239000012530 fluid Substances 0.000 description 4
• 230000005714 functional activity Effects 0.000 description 4
• 230000003301 hydrolyzing effect Effects 0.000 description 4
• 229910052588 hydroxylapatite Inorganic materials 0.000 description 4
• 230000001506 immunosuppresive effect Effects 0.000 description 4
• 230000006872 improvement Effects 0.000 description 4
• 230000002458 infectious effect Effects 0.000 description 4
• 230000010354 integration Effects 0.000 description 4
• 210000002414 leg Anatomy 0.000 description 4
• 108020004999 messenger RNA Proteins 0.000 description 4
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
• 230000004048 modification Effects 0.000 description 4
• 238000012986 modification Methods 0.000 description 4
• 230000002107 myocardial effect Effects 0.000 description 4
• 231100000252 nontoxic Toxicity 0.000 description 4
• 230000003000 nontoxic effect Effects 0.000 description 4
• RWOAVOYBVRQNIZ-BFHYXJOUSA-N p-nitrophenyl thymidine 5'-monophosphate Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(=O)OC=2C=CC(=CC=2)[N+]([O-])=O)[C@@H](O)C1 RWOAVOYBVRQNIZ-BFHYXJOUSA-N 0.000 description 4
• XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 4
• 108010079892 phosphoglycerol kinase Proteins 0.000 description 4
• 229920001223 polyethylene glycol Polymers 0.000 description 4
• 238000011002 quantification Methods 0.000 description 4
• 239000000523 sample Substances 0.000 description 4
• 210000002027 skeletal muscle Anatomy 0.000 description 4
• 239000000126 substance Substances 0.000 description 4
• 238000010361 transduction Methods 0.000 description 4
• 230000026683 transduction Effects 0.000 description 4
• 238000012546 transfer Methods 0.000 description 4
• 239000002753 trypsin inhibitor Substances 0.000 description 4
• 210000005239 tubule Anatomy 0.000 description 4
• 241001529453 unidentified herpesvirus Species 0.000 description 4
• 230000002792 vascular Effects 0.000 description 4
• 210000005166 vasculature Anatomy 0.000 description 4
• 230000003442 weekly effect Effects 0.000 description 4
• QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
• 101100225890 Aplysia californica ENPP gene Proteins 0.000 description 3
• 201000001320 Atherosclerosis Diseases 0.000 description 3
• 208000010392 Bone Fractures Diseases 0.000 description 3
• 206010070918 Bone deformity Diseases 0.000 description 3
• 108020004705 Codon Proteins 0.000 description 3
• 108010036949 Cyclosporine Proteins 0.000 description 3
• 102100021977 Ectonucleotide pyrophosphatase/phosphodiesterase family member 2 Human genes 0.000 description 3
• 102100021962 Ectonucleotide pyrophosphatase/phosphodiesterase family member 5 Human genes 0.000 description 3
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
• 102100024802 Fibroblast growth factor 23 Human genes 0.000 description 3
• 241000282412 Homo Species 0.000 description 3
• 101000793686 Homo sapiens Azurocidin Proteins 0.000 description 3
• 101000897035 Homo sapiens Ectonucleotide pyrophosphatase/phosphodiesterase family member 2 Proteins 0.000 description 3
• 101000897063 Homo sapiens Ectonucleotide pyrophosphatase/phosphodiesterase family member 5 Proteins 0.000 description 3
• 102000003839 Human Proteins Human genes 0.000 description 3
• 108090000144 Human Proteins Proteins 0.000 description 3
• 108060003951 Immunoglobulin Proteins 0.000 description 3
• FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 3
• 241000713869 Moloney murine leukemia virus Species 0.000 description 3
• 206010028570 Myelopathy Diseases 0.000 description 3
• 101800000511 Non-structural protein 2 Proteins 0.000 description 3
• 239000002202 Polyethylene glycol Substances 0.000 description 3
• 206010037779 Radiculopathy Diseases 0.000 description 3
• 241000710961 Semliki Forest virus Species 0.000 description 3
• 208000020221 Short stature Diseases 0.000 description 3
• 241000713311 Simian immunodeficiency virus Species 0.000 description 3
• 108020004682 Single-Stranded DNA Proteins 0.000 description 3
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
• 108091027544 Subgenomic mRNA Proteins 0.000 description 3
• 102000006601 Thymidine Kinase Human genes 0.000 description 3
• 108020004440 Thymidine kinase Proteins 0.000 description 3
• 206010047626 Vitamin D Deficiency Diseases 0.000 description 3
• 235000001014 amino acid Nutrition 0.000 description 3
• 125000000539 amino acid group Chemical group 0.000 description 3
• 230000001174 ascending effect Effects 0.000 description 3
• LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 3
• 230000008901 benefit Effects 0.000 description 3
• 230000017531 blood circulation Effects 0.000 description 3
• 238000009534 blood test Methods 0.000 description 3
• 210000004899 c-terminal region Anatomy 0.000 description 3
• 239000005018 casein Substances 0.000 description 3
• 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 3
• 235000021240 caseins Nutrition 0.000 description 3
• 239000001913 cellulose Substances 0.000 description 3
• 229920002678 cellulose Polymers 0.000 description 3
• 210000000349 chromosome Anatomy 0.000 description 3
• 238000000975 co-precipitation Methods 0.000 description 3
• 230000001276 controlling effect Effects 0.000 description 3
• 230000000120 cytopathologic effect Effects 0.000 description 3
• 230000007547 defect Effects 0.000 description 3
• 238000000502 dialysis Methods 0.000 description 3
• 239000003085 diluting agent Substances 0.000 description 3
• 235000019441 ethanol Nutrition 0.000 description 3
• 210000003414 extremity Anatomy 0.000 description 3
• 210000005003 heart tissue Anatomy 0.000 description 3
• 208000011111 hypophosphatemic rickets Diseases 0.000 description 3
• 102000018358 immunoglobulin Human genes 0.000 description 3
• 230000001976 improved effect Effects 0.000 description 3
• 238000000338 in vitro Methods 0.000 description 3
• 239000007788 liquid Substances 0.000 description 3
• 210000003141 lower extremity Anatomy 0.000 description 3
• 210000004072 lung Anatomy 0.000 description 3
• 230000001404 mediated effect Effects 0.000 description 3
• 210000004379 membrane Anatomy 0.000 description 3
• 239000012528 membrane Substances 0.000 description 3
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
• 238000012544 monitoring process Methods 0.000 description 3
• 238000002703 mutagenesis Methods 0.000 description 3
• 231100000350 mutagenesis Toxicity 0.000 description 3
• 210000003739 neck Anatomy 0.000 description 3
• 235000016709 nutrition Nutrition 0.000 description 3
• 208000035824 paresthesia Diseases 0.000 description 3
• 239000008188 pellet Substances 0.000 description 3
• 230000000737 periodic effect Effects 0.000 description 3
• 230000003389 potentiating effect Effects 0.000 description 3
• 239000000843 powder Substances 0.000 description 3
• 230000002028 premature Effects 0.000 description 3
• 238000002360 preparation method Methods 0.000 description 3
• 239000003755 preservative agent Substances 0.000 description 3
• 231100000272 reduced body weight Toxicity 0.000 description 3
• 238000011808 rodent model Methods 0.000 description 3
• 230000028327 secretion Effects 0.000 description 3
• 210000003625 skull Anatomy 0.000 description 3
• 101150027996 smb1 gene Proteins 0.000 description 3
• 238000010186 staining Methods 0.000 description 3
• 238000007920 subcutaneous administration Methods 0.000 description 3
• 238000006467 substitution reaction Methods 0.000 description 3
• 239000006228 supernatant Substances 0.000 description 3
• 239000000375 suspending agent Substances 0.000 description 3
• 239000000725 suspension Substances 0.000 description 3
• 230000008961 swelling Effects 0.000 description 3
• 208000011580 syndromic disease Diseases 0.000 description 3
• 238000003786 synthesis reaction Methods 0.000 description 3
• 230000008685 targeting Effects 0.000 description 3
• 238000002604 ultrasonography Methods 0.000 description 3
• 241001430294 unidentified retrovirus Species 0.000 description 3
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
• XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 0.000 description 2
• XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 2
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
• 102100022900 Actin, cytoplasmic 1 Human genes 0.000 description 2
• 108010085238 Actins Proteins 0.000 description 2
• 102100025683 Alkaline phosphatase, tissue-nonspecific isozyme Human genes 0.000 description 2
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
• 239000005695 Ammonium acetate Substances 0.000 description 2
• 208000037411 Aortic calcification Diseases 0.000 description 2
• 206010003210 Arteriosclerosis Diseases 0.000 description 2
• 206010003211 Arteriosclerosis coronary artery Diseases 0.000 description 2
• 208000006820 Arthralgia Diseases 0.000 description 2
• 208000037260 Atherosclerotic Plaque Diseases 0.000 description 2
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
• 241000271566 Aves Species 0.000 description 2
• 102100030802 Beta-2-glycoprotein 1 Human genes 0.000 description 2
• UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
• 241000282472 Canis lupus familiaris Species 0.000 description 2
• 208000006029 Cardiomegaly Diseases 0.000 description 2
• 208000024172 Cardiovascular disease Diseases 0.000 description 2
• 206010050217 Cervical radiculopathy Diseases 0.000 description 2
• 208000016216 Choristoma Diseases 0.000 description 2
• 108700010070 Codon Usage Proteins 0.000 description 2
• 229920002261 Corn starch Polymers 0.000 description 2
• 208000009283 Craniosynostoses Diseases 0.000 description 2
• 206010049889 Craniosynostosis Diseases 0.000 description 2
• 206010011703 Cyanosis Diseases 0.000 description 2
• 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 2
• 108010053770 Deoxyribonucleases Proteins 0.000 description 2
• 102000016911 Deoxyribonucleases Human genes 0.000 description 2
• 101100118093 Drosophila melanogaster eEF1alpha2 gene Proteins 0.000 description 2
• 238000002965 ELISA Methods 0.000 description 2
• 241000283073 Equus caballus Species 0.000 description 2
• 206010015719 Exsanguination Diseases 0.000 description 2
• 102000001690 Factor VIII Human genes 0.000 description 2
• 108010054218 Factor VIII Proteins 0.000 description 2
• 241000282326 Felis catus Species 0.000 description 2
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
• 206010017076 Fracture Diseases 0.000 description 2
• 208000010300 Genu Varum Diseases 0.000 description 2
• HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
• 201000003676 Hereditary hypophosphatemic rickets with hypercalciuria Diseases 0.000 description 2
• 101000574445 Homo sapiens Alkaline phosphatase, tissue-nonspecific isozyme Proteins 0.000 description 2
• 101000823116 Homo sapiens Alpha-1-antitrypsin Proteins 0.000 description 2
• 241001135569 Human adenovirus 5 Species 0.000 description 2
• 241000701044 Human gammaherpesvirus 4 Species 0.000 description 2
• 208000037147 Hypercalcaemia Diseases 0.000 description 2
• 201000002980 Hyperparathyroidism Diseases 0.000 description 2
• 102000018251 Hypoxanthine Phosphoribosyltransferase Human genes 0.000 description 2
• 108010091358 Hypoxanthine Phosphoribosyltransferase Proteins 0.000 description 2
• XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 2
• 206010062016 Immunosuppression Diseases 0.000 description 2
• 206010061218 Inflammation Diseases 0.000 description 2
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
• 108010059343 MM Form Creatine Kinase Proteins 0.000 description 2
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
• 208000034819 Mobility Limitation Diseases 0.000 description 2
• 241001529936 Murinae Species 0.000 description 2
• 101100011757 Mus musculus Enpp1 gene Proteins 0.000 description 2
• 208000007101 Muscle Cramp Diseases 0.000 description 2
• 206010028594 Myocardial fibrosis Diseases 0.000 description 2
• 102000016349 Myosin Light Chains Human genes 0.000 description 2
• 108010067385 Myosin Light Chains Proteins 0.000 description 2
• NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
• 206010028813 Nausea Diseases 0.000 description 2
• 206010028851 Necrosis Diseases 0.000 description 2
• 206010028980 Neoplasm Diseases 0.000 description 2
• 206010030113 Oedema Diseases 0.000 description 2
• 101150004854 PHEX gene Proteins 0.000 description 2
• 206010033733 Papule Diseases 0.000 description 2
• 208000031481 Pathologic Constriction Diseases 0.000 description 2
• 102000010292 Peptide Elongation Factor 1 Human genes 0.000 description 2
• 108010077524 Peptide Elongation Factor 1 Proteins 0.000 description 2
• 102000014190 Phosphatidylcholine-sterol O-acyltransferase Human genes 0.000 description 2
• 108010011964 Phosphatidylcholine-sterol O-acyltransferase Proteins 0.000 description 2
• 102000011755 Phosphoglycerate Kinase Human genes 0.000 description 2
• 239000004365 Protease Substances 0.000 description 2
• 108020005115 Pyruvate Kinase Proteins 0.000 description 2
• 102000013009 Pyruvate Kinase Human genes 0.000 description 2
• 108020004511 Recombinant DNA Proteins 0.000 description 2
• 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
• 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
• 208000001647 Renal Insufficiency Diseases 0.000 description 2
• 108010034546 Serratia marcescens nuclease Proteins 0.000 description 2
• 108010051611 Signal Recognition Particle Proteins 0.000 description 2
• 102000013598 Signal recognition particle Human genes 0.000 description 2
• 241000282887 Suidae Species 0.000 description 2
• 101001099217 Thermotoga maritima (strain ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8) Triosephosphate isomerase Proteins 0.000 description 2
• 102000002248 Thyroxine-Binding Globulin Human genes 0.000 description 2
• 108010000259 Thyroxine-Binding Globulin Proteins 0.000 description 2
• 108091023040 Transcription factor Proteins 0.000 description 2
• 102000040945 Transcription factor Human genes 0.000 description 2
• 102100023935 Transmembrane glycoprotein NMB Human genes 0.000 description 2
• 239000007983 Tris buffer Substances 0.000 description 2
• HSCJRCZFDFQWRP-RDKQLNKOSA-N UDP-D-glucose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)OC1OP(O)(=O)OP(O)(=O)OC[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C(NC(=O)C=C2)=O)O1 HSCJRCZFDFQWRP-RDKQLNKOSA-N 0.000 description 2
• 241000710959 Venezuelan equine encephalitis virus Species 0.000 description 2
• 108020000999 Viral RNA Proteins 0.000 description 2
• 238000002835 absorbance Methods 0.000 description 2
• 239000002253 acid Substances 0.000 description 2
• RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 2
• 230000004913 activation Effects 0.000 description 2
• 239000012190 activator Substances 0.000 description 2
• 230000001154 acute effect Effects 0.000 description 2
• 230000004075 alteration Effects 0.000 description 2
• 235000019257 ammonium acetate Nutrition 0.000 description 2
• 229940043376 ammonium acetate Drugs 0.000 description 2
• 239000003242 anti bacterial agent Substances 0.000 description 2
• 229940045686 antimetabolites antineoplastic purine analogs Drugs 0.000 description 2
• 210000002376 aorta thoracic Anatomy 0.000 description 2
• 208000011775 arteriosclerosis disease Diseases 0.000 description 2
• 201000003672 autosomal recessive hypophosphatemic rickets Diseases 0.000 description 2
• 229960002170 azathioprine Drugs 0.000 description 2
• 230000001580 bacterial effect Effects 0.000 description 2
• 210000002469 basement membrane Anatomy 0.000 description 2
• 108010023562 beta 2-Glycoprotein I Proteins 0.000 description 2
• DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 2
• 230000003115 biocidal effect Effects 0.000 description 2
• 239000012620 biological material Substances 0.000 description 2
• 230000037182 bone density Effects 0.000 description 2
• 239000000872 buffer Substances 0.000 description 2
• 229960005084 calcitriol Drugs 0.000 description 2
• GMRQFYUYWCNGIN-NKMMMXOESA-N calcitriol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CCCC(C)(C)O)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C GMRQFYUYWCNGIN-NKMMMXOESA-N 0.000 description 2
• 239000001110 calcium chloride Substances 0.000 description 2
• 229910001628 calcium chloride Inorganic materials 0.000 description 2
• 159000000007 calcium salts Chemical group 0.000 description 2
• 201000011510 cancer Diseases 0.000 description 2
• 230000001413 cellular effect Effects 0.000 description 2
• 239000007795 chemical reaction product Substances 0.000 description 2
• JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 2
• 238000004587 chromatography analysis Methods 0.000 description 2
• 230000004087 circulation Effects 0.000 description 2
• 238000009535 clinical urine test Methods 0.000 description 2
• 238000010367 cloning Methods 0.000 description 2
• 239000002299 complementary DNA Substances 0.000 description 2
• 230000021615 conjugation Effects 0.000 description 2
• 239000008120 corn starch Substances 0.000 description 2
• 229940099112 cornstarch Drugs 0.000 description 2
• 239000013078 crystal Substances 0.000 description 2
• 230000001086 cytosolic effect Effects 0.000 description 2
• 239000000824 cytostatic agent Substances 0.000 description 2
• 230000001085 cytostatic effect Effects 0.000 description 2
• 230000034994 death Effects 0.000 description 2
• 239000000975 dye Substances 0.000 description 2
• 230000002526 effect on cardiovascular system Effects 0.000 description 2
• 238000004520 electroporation Methods 0.000 description 2
• 230000007613 environmental effect Effects 0.000 description 2
• 238000007824 enzymatic assay Methods 0.000 description 2
• 238000006911 enzymatic reaction Methods 0.000 description 2
• YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 2
• 238000011156 evaluation Methods 0.000 description 2
• 230000017188 evasion or tolerance of host immune response Effects 0.000 description 2
• 230000029142 excretion Effects 0.000 description 2
• 229960000301 factor viii Drugs 0.000 description 2
• 239000003925 fat Substances 0.000 description 2
• 206010016256 fatigue Diseases 0.000 description 2
• 235000019253 formic acid Nutrition 0.000 description 2
• 239000003862 glucocorticoid Substances 0.000 description 2
• 230000012010 growth Effects 0.000 description 2
• 239000001963 growth medium Substances 0.000 description 2
• 210000004349 growth plate Anatomy 0.000 description 2
• 230000002440 hepatic effect Effects 0.000 description 2
• 210000003494 hepatocyte Anatomy 0.000 description 2
• 208000014092 hereditary hypophosphatemic rickets Diseases 0.000 description 2
• 230000013632 homeostatic process Effects 0.000 description 2
• 229940088597 hormone Drugs 0.000 description 2
• 239000005556 hormone Substances 0.000 description 2
• 102000051631 human SERPINA1 Human genes 0.000 description 2
• JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
• 230000000148 hypercalcaemia Effects 0.000 description 2
• 208000030915 hypercalcemia disease Diseases 0.000 description 2
• 239000012216 imaging agent Substances 0.000 description 2
• 230000001771 impaired effect Effects 0.000 description 2
• 238000011534 incubation Methods 0.000 description 2
• 230000008595 infiltration Effects 0.000 description 2
• 238000001764 infiltration Methods 0.000 description 2
• 230000004054 inflammatory process Effects 0.000 description 2
• 239000004615 ingredient Substances 0.000 description 2
• 230000003993 interaction Effects 0.000 description 2
• 238000001361 intraarterial administration Methods 0.000 description 2
• 230000003834 intracellular effect Effects 0.000 description 2
• 238000007918 intramuscular administration Methods 0.000 description 2
• 239000007928 intraperitoneal injection Substances 0.000 description 2
• 238000010253 intravenous injection Methods 0.000 description 2
• 208000017169 kidney disease Diseases 0.000 description 2
• 201000006370 kidney failure Diseases 0.000 description 2
• 238000011813 knockout mouse model Methods 0.000 description 2
• VHOGYURTWQBHIL-UHFFFAOYSA-N leflunomide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)C(F)(F)F)=C1C VHOGYURTWQBHIL-UHFFFAOYSA-N 0.000 description 2
• 210000003041 ligament Anatomy 0.000 description 2
• 108010026228 mRNA guanylyltransferase Proteins 0.000 description 2
• 239000011777 magnesium Substances 0.000 description 2
• 229910052749 magnesium Inorganic materials 0.000 description 2
• 229910001629 magnesium chloride Inorganic materials 0.000 description 2
• 238000002595 magnetic resonance imaging Methods 0.000 description 2
• 229960000485 methotrexate Drugs 0.000 description 2
• 230000000877 morphologic effect Effects 0.000 description 2
• 230000003387 muscular Effects 0.000 description 2
• 230000008693 nausea Effects 0.000 description 2
• 230000017074 necrotic cell death Effects 0.000 description 2
• 238000013059 nephrectomy Methods 0.000 description 2
• 238000005457 optimization Methods 0.000 description 2
• 238000007911 parenteral administration Methods 0.000 description 2
• 239000008177 pharmaceutical agent Substances 0.000 description 2
• 239000000546 pharmaceutical excipient Substances 0.000 description 2
• 230000035790 physiological processes and functions Effects 0.000 description 2
• 238000001556 precipitation Methods 0.000 description 2
• 208000037821 progressive disease Diseases 0.000 description 2
• 230000017854 proteolysis Effects 0.000 description 2
• 230000002685 pulmonary effect Effects 0.000 description 2
• 150000003212 purines Chemical class 0.000 description 2
• 239000000700 radioactive tracer Substances 0.000 description 2
• 238000011552 rat model Methods 0.000 description 2
• 239000011541 reaction mixture Substances 0.000 description 2
• 238000003753 real-time PCR Methods 0.000 description 2
• 210000005084 renal tissue Anatomy 0.000 description 2
• 230000001177 retroviral effect Effects 0.000 description 2
• 150000003839 salts Chemical class 0.000 description 2
• 238000012216 screening Methods 0.000 description 2
• 239000007787 solid Substances 0.000 description 2
• 241000894007 species Species 0.000 description 2
• 239000003381 stabilizer Substances 0.000 description 2
• 230000000087 stabilizing effect Effects 0.000 description 2
• 230000036262 stenosis Effects 0.000 description 2
• 208000037804 stenosis Diseases 0.000 description 2
• 239000004575 stone Substances 0.000 description 2
• 238000007910 systemic administration Methods 0.000 description 2
• 230000009885 systemic effect Effects 0.000 description 2
• 229940037128 systemic glucocorticoids Drugs 0.000 description 2
• 229940124597 therapeutic agent Drugs 0.000 description 2
• 238000002560 therapeutic procedure Methods 0.000 description 2
• XUIIKFGFIJCVMT-UHFFFAOYSA-N thyroxine-binding globulin Natural products IC1=CC(CC([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-UHFFFAOYSA-N 0.000 description 2
• 210000002303 tibia Anatomy 0.000 description 2
• 238000013519 translation Methods 0.000 description 2
• 108091007466 transmembrane glycoproteins Proteins 0.000 description 2
• 230000032258 transport Effects 0.000 description 2
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
• 230000010415 tropism Effects 0.000 description 2
• 210000001364 upper extremity Anatomy 0.000 description 2
• DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 2
• 229940045145 uridine Drugs 0.000 description 2
• 210000001635 urinary tract Anatomy 0.000 description 2
• 230000002861 ventricular Effects 0.000 description 2
• 238000007794 visualization technique Methods 0.000 description 2
• 230000003313 weakening effect Effects 0.000 description 2
• 230000004580 weight loss Effects 0.000 description 2
• GMRQFYUYWCNGIN-UHFFFAOYSA-N 1,25-Dihydroxy-vitamin D3' Natural products C1CCC2(C)C(C(CCCC(C)(C)O)C)CCC2C1=CC=C1CC(O)CC(O)C1=C GMRQFYUYWCNGIN-UHFFFAOYSA-N 0.000 description 1
• KUBWJGWIWGGEPZ-UHFFFAOYSA-N 1-[amino(ethoxy)phosphoryl]oxy-4-nitrobenzene Chemical compound CCOP(N)(=O)OC1=CC=C([N+]([O-])=O)C=C1 KUBWJGWIWGGEPZ-UHFFFAOYSA-N 0.000 description 1
• NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 1
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
• CRIZPXKICGBNKG-UHFFFAOYSA-N 3,7-dihydropurin-2-one Chemical compound OC1=NC=C2NC=NC2=N1 CRIZPXKICGBNKG-UHFFFAOYSA-N 0.000 description 1
• FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
• BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 1
• 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 description 1
• 101150008034 AZU1 gene Proteins 0.000 description 1
• 241000251468 Actinopterygii Species 0.000 description 1
• 241000649046 Adeno-associated virus 11 Species 0.000 description 1
• 101100524317 Adeno-associated virus 2 (isolate Srivastava/1982) Rep40 gene Proteins 0.000 description 1
• 101100524321 Adeno-associated virus 2 (isolate Srivastava/1982) Rep68 gene Proteins 0.000 description 1
• 102100036664 Adenosine deaminase Human genes 0.000 description 1
• 102000007698 Alcohol dehydrogenase Human genes 0.000 description 1
• 108010021809 Alcohol dehydrogenase Proteins 0.000 description 1
• 235000019489 Almond oil Nutrition 0.000 description 1
• 102100022524 Alpha-1-antichymotrypsin Human genes 0.000 description 1
• 208000024827 Alzheimer disease Diseases 0.000 description 1
• 206010002091 Anaesthesia Diseases 0.000 description 1
• 208000005598 Angioid Streaks Diseases 0.000 description 1
• 101710081722 Antitrypsin Proteins 0.000 description 1
• 102000005666 Apolipoprotein A-I Human genes 0.000 description 1
• 108010059886 Apolipoprotein A-I Proteins 0.000 description 1
• 102100029470 Apolipoprotein E Human genes 0.000 description 1
• 101710095339 Apolipoprotein E Proteins 0.000 description 1
• 102000013918 Apolipoproteins E Human genes 0.000 description 1
• 108010025628 Apolipoproteins E Proteins 0.000 description 1
• 206010060965 Arterial stenosis Diseases 0.000 description 1
• 206010003694 Atrophy Diseases 0.000 description 1
• 206010069632 Bladder dysfunction Diseases 0.000 description 1
• 108010006654 Bleomycin Proteins 0.000 description 1
• 208000019838 Blood disease Diseases 0.000 description 1
• 208000011491 Bowing of the legs Diseases 0.000 description 1
• 208000003174 Brain Neoplasms Diseases 0.000 description 1
• 208000014644 Brain disease Diseases 0.000 description 1
• 238000011740 C57BL/6 mouse Methods 0.000 description 1
• 229940124292 CD20 monoclonal antibody Drugs 0.000 description 1
• 241001126923 Calcarea Species 0.000 description 1
• 206010007027 Calculus urinary Diseases 0.000 description 1
• 241000282465 Canis Species 0.000 description 1
• 101150044789 Cap gene Proteins 0.000 description 1
• 241000283707 Capra Species 0.000 description 1
• 241000700198 Cavia Species 0.000 description 1
• 206010066296 Cerebral calcification Diseases 0.000 description 1
• 108010075016 Ceruloplasmin Proteins 0.000 description 1
• 241000282552 Chlorocebus aethiops Species 0.000 description 1
• 208000033825 Chorioretinal atrophy Diseases 0.000 description 1
• 108010035532 Collagen Proteins 0.000 description 1
• 102000008186 Collagen Human genes 0.000 description 1
• 108010027644 Complement C9 Proteins 0.000 description 1
• 102000016550 Complement Factor H Human genes 0.000 description 1
• 108010053085 Complement Factor H Proteins 0.000 description 1
• 108010069112 Complement System Proteins Proteins 0.000 description 1
• 102000000989 Complement System Proteins Human genes 0.000 description 1
• 102100035431 Complement factor I Human genes 0.000 description 1
• 208000034656 Contusions Diseases 0.000 description 1
• 241000699800 Cricetinae Species 0.000 description 1
• 241000699802 Cricetulus griseus Species 0.000 description 1
• 206010011778 Cystinuria Diseases 0.000 description 1
• 101150026402 DBP gene Proteins 0.000 description 1
• 239000004470 DL Methionine Substances 0.000 description 1
• 102000016559 DNA Primase Human genes 0.000 description 1
• 108010092681 DNA Primase Proteins 0.000 description 1
• 102000003844 DNA helicases Human genes 0.000 description 1
• 108090000133 DNA helicases Proteins 0.000 description 1
• 241000450599 DNA viruses Species 0.000 description 1
• 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
• 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
• 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
• 108010092160 Dactinomycin Proteins 0.000 description 1
• 206010011878 Deafness Diseases 0.000 description 1
• 102100022375 Dentin matrix acidic phosphoprotein 1 Human genes 0.000 description 1
• 229920002307 Dextran Polymers 0.000 description 1
• 101001098806 Dictyostelium discoideum cGMP-specific 3',5'-cGMP phosphodiesterase 3 Proteins 0.000 description 1
• 201000010374 Down Syndrome Diseases 0.000 description 1
• 206010013886 Dysaesthesia Diseases 0.000 description 1
• 208000000059 Dyspnea Diseases 0.000 description 1
• 206010052273 Dystrophic calcification Diseases 0.000 description 1
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
• 238000011891 EIA kit Methods 0.000 description 1
• 238000008157 ELISA kit Methods 0.000 description 1
• 101150023177 Enpp3 gene Proteins 0.000 description 1
• 241000283086 Equidae Species 0.000 description 1
• 241000713730 Equine infectious anemia virus Species 0.000 description 1
• 108091029865 Exogenous DNA Proteins 0.000 description 1
• 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
• 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
• 102000009109 Fc receptors Human genes 0.000 description 1
• 108010087819 Fc receptors Proteins 0.000 description 1
• 241000713800 Feline immunodeficiency virus Species 0.000 description 1
• 206010016654 Fibrosis Diseases 0.000 description 1
• GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
• 206010017577 Gait disturbance Diseases 0.000 description 1
• 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
• 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
• 206010018341 Gliosis Diseases 0.000 description 1
• YPFFHGRJCUBXPX-NHCYSSNCSA-N Gln-Pro-Val Chemical compound CC(C)[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CCC(N)=O)C(O)=O YPFFHGRJCUBXPX-NHCYSSNCSA-N 0.000 description 1
• 102000006395 Globulins Human genes 0.000 description 1
• 108010044091 Globulins Proteins 0.000 description 1
• RBXSZQRSEGYDFG-GUBZILKMSA-N Glu-Lys-Ser Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O RBXSZQRSEGYDFG-GUBZILKMSA-N 0.000 description 1
• DXVOKNVIKORTHQ-GUBZILKMSA-N Glu-Pro-Glu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O DXVOKNVIKORTHQ-GUBZILKMSA-N 0.000 description 1
• ZYRXTRTUCAVNBQ-GVXVVHGQSA-N Glu-Val-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCC(=O)O)N ZYRXTRTUCAVNBQ-GVXVVHGQSA-N 0.000 description 1
• SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
• 102000003886 Glycoproteins Human genes 0.000 description 1
• 108090000288 Glycoproteins Proteins 0.000 description 1
• 102100034471 H(+)/Cl(-) exchange transporter 5 Human genes 0.000 description 1
• 108050005077 Haptoglobin Proteins 0.000 description 1
• 102000014702 Haptoglobin Human genes 0.000 description 1
• 229920002971 Heparan sulfate Polymers 0.000 description 1
• 208000005176 Hepatitis C Diseases 0.000 description 1
• 208000007514 Herpes zoster Diseases 0.000 description 1
• 229920000209 Hexadimethrine bromide Polymers 0.000 description 1
• PQKCQZHAGILVIM-NKIYYHGXSA-N His-Glu-Thr Chemical compound C[C@@H](O)[C@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)Cc1cnc[nH]1)C(O)=O PQKCQZHAGILVIM-NKIYYHGXSA-N 0.000 description 1
• WZBLRQQCDYYRTD-SIXJUCDHSA-N His-Ile-Trp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)NC(=O)[C@H](CC3=CN=CN3)N WZBLRQQCDYYRTD-SIXJUCDHSA-N 0.000 description 1
• 101000804518 Homo sapiens Cyclin-D-binding Myb-like transcription factor 1 Proteins 0.000 description 1
• 101000901629 Homo sapiens Dentin matrix acidic phosphoprotein 1 Proteins 0.000 description 1
• 101000642577 Homo sapiens Growth hormone variant Proteins 0.000 description 1
• 101000710225 Homo sapiens H(+)/Cl(-) exchange transporter 5 Proteins 0.000 description 1
• 101000579123 Homo sapiens Phosphoglycerate kinase 1 Proteins 0.000 description 1
• 241000701109 Human adenovirus 2 Species 0.000 description 1
• 241000700588 Human alphaherpesvirus 1 Species 0.000 description 1
• 241000701085 Human alphaherpesvirus 3 Species 0.000 description 1
• 101001042049 Human herpesvirus 1 (strain 17) Transcriptional regulator ICP22 Proteins 0.000 description 1
• 101000999690 Human herpesvirus 2 (strain HG52) E3 ubiquitin ligase ICP22 Proteins 0.000 description 1
• 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
• 208000025500 Hutchinson-Gilford progeria syndrome Diseases 0.000 description 1
• 206010020590 Hypercalciuria Diseases 0.000 description 1
• 208000004044 Hypesthesia Diseases 0.000 description 1
• 206010049933 Hypophosphatasia Diseases 0.000 description 1
• VWFWJPJMAFRNET-MQWMPURMSA-N IACI Chemical compound C1=CC=C2C([C@@H](O)[C@@H]3CC4CCN3C[C@@H]4CC)=CC=NC2=C1NC(=O)C1=CC([125I])=C(N=[N+]=[N-])C=C1O VWFWJPJMAFRNET-MQWMPURMSA-N 0.000 description 1
• 101150027427 ICP4 gene Proteins 0.000 description 1
• HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
• 102100026120 IgG receptor FcRn large subunit p51 Human genes 0.000 description 1
• 101710177940 IgG receptor FcRn large subunit p51 Proteins 0.000 description 1
• 108700002232 Immediate-Early Genes Proteins 0.000 description 1
• 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 1
• 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 1
• 102000000521 Immunophilins Human genes 0.000 description 1
• 108010016648 Immunophilins Proteins 0.000 description 1
• 208000026350 Inborn Genetic disease Diseases 0.000 description 1
• 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
• 206010022562 Intermittent claudication Diseases 0.000 description 1
• PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
• 239000007836 KH2PO4 Substances 0.000 description 1
• 206010062061 Knee deformity Diseases 0.000 description 1
• 102000007330 LDL Lipoproteins Human genes 0.000 description 1
• 108010007622 LDL Lipoproteins Proteins 0.000 description 1
• 229910025794 LaB6 Inorganic materials 0.000 description 1
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
• 240000007472 Leucaena leucocephala Species 0.000 description 1
• 208000009829 Lewy Body Disease Diseases 0.000 description 1
• 201000002832 Lewy body dementia Diseases 0.000 description 1
• NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
• MDDUIRLQCYVRDO-NHCYSSNCSA-N Lys-Val-Asn Chemical compound NC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CCCCN MDDUIRLQCYVRDO-NHCYSSNCSA-N 0.000 description 1
• 101710141452 Major surface glycoprotein G Proteins 0.000 description 1
• 239000005913 Maltodextrin Substances 0.000 description 1
• 229920002774 Maltodextrin Polymers 0.000 description 1
• 108010052285 Membrane Proteins Proteins 0.000 description 1
• KQBJYJXPZBNEIK-DCAQKATOSA-N Met-Glu-Arg Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(O)=O)CCCNC(N)=N KQBJYJXPZBNEIK-DCAQKATOSA-N 0.000 description 1
• VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
• 108090000143 Mouse Proteins Proteins 0.000 description 1
• 241000713333 Mouse mammary tumor virus Species 0.000 description 1
• 101000930477 Mus musculus Albumin Proteins 0.000 description 1
• 101000617395 Mus musculus Probable peptidyl-tRNA hydrolase Proteins 0.000 description 1
• 208000008238 Muscle Spasticity Diseases 0.000 description 1
• 208000010428 Muscle Weakness Diseases 0.000 description 1
• 206010028372 Muscular weakness Diseases 0.000 description 1
• 101100030372 Nicotiana tabacum NPP5 gene Proteins 0.000 description 1
• 108020004485 Nonsense Codon Proteins 0.000 description 1
• 108091005461 Nucleic proteins Proteins 0.000 description 1
• CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
• 108010064527 OSM-LIF Receptors Proteins 0.000 description 1
• 108091034117 Oligonucleotide Proteins 0.000 description 1
• 102000004264 Osteopontin Human genes 0.000 description 1
• 108010081689 Osteopontin Proteins 0.000 description 1
• 108700005081 Overlapping Genes Proteins 0.000 description 1
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
• KJWZYMMLVHIVSU-IYCNHOCDSA-N PGK1 Chemical compound CCCCC[C@H](O)\C=C\[C@@H]1[C@@H](CCCCCCC(O)=O)C(=O)CC1=O KJWZYMMLVHIVSU-IYCNHOCDSA-N 0.000 description 1
• 241000282579 Pan Species 0.000 description 1
• 108090000526 Papain Proteins 0.000 description 1
• 241001631646 Papillomaviridae Species 0.000 description 1
• 229930040373 Paraformaldehyde Natural products 0.000 description 1
• 208000018737 Parkinson disease Diseases 0.000 description 1
• 241000701945 Parvoviridae Species 0.000 description 1
• 208000037273 Pathologic Processes Diseases 0.000 description 1
• 241001494479 Pecora Species 0.000 description 1
• 108091005804 Peptidases Proteins 0.000 description 1
• 102000035195 Peptidases Human genes 0.000 description 1
• 208000001300 Perinatal Death Diseases 0.000 description 1
• 208000018262 Peripheral vascular disease Diseases 0.000 description 1
• APJPXSFJBMMOLW-KBPBESRZSA-N Phe-Gly-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CC1=CC=CC=C1 APJPXSFJBMMOLW-KBPBESRZSA-N 0.000 description 1
• 108010010677 Phosphodiesterase I Proteins 0.000 description 1
• 102100028251 Phosphoglycerate kinase 1 Human genes 0.000 description 1
• 241000709664 Picornaviridae Species 0.000 description 1
• 240000006711 Pistacia vera Species 0.000 description 1
• 102100038124 Plasminogen Human genes 0.000 description 1
• 108010051456 Plasminogen Proteins 0.000 description 1
• 229920000608 Polyaspartic Polymers 0.000 description 1
• 229920002594 Polyethylene Glycol 8000 Polymers 0.000 description 1
• 229920002873 Polyethylenimine Polymers 0.000 description 1
• 108010076039 Polyproteins Proteins 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 102000007584 Prealbumin Human genes 0.000 description 1
• 108010071690 Prealbumin Proteins 0.000 description 1
• 208000007932 Progeria Diseases 0.000 description 1
• 101710160093 Progressive ankylosis protein Proteins 0.000 description 1
• 108010007568 Protamines Proteins 0.000 description 1
• 108010029485 Protein Isoforms Proteins 0.000 description 1
• 102000001708 Protein Isoforms Human genes 0.000 description 1
• 229940123573 Protein synthesis inhibitor Drugs 0.000 description 1
• 241000125945 Protoparvovirus Species 0.000 description 1
• 208000003251 Pruritus Diseases 0.000 description 1
• 102000009572 RNA Polymerase II Human genes 0.000 description 1
• 108010009460 RNA Polymerase II Proteins 0.000 description 1
• 108091081062 Repeated sequence (DNA) Proteins 0.000 description 1
• 108010034634 Repressor Proteins Proteins 0.000 description 1
• 102000009661 Repressor Proteins Human genes 0.000 description 1
• 208000018569 Respiratory Tract disease Diseases 0.000 description 1
• 208000037111 Retinal Hemorrhage Diseases 0.000 description 1
• 241000712907 Retroviridae Species 0.000 description 1
• 208000005074 Retroviridae Infections Diseases 0.000 description 1
• 241000219061 Rheum Species 0.000 description 1
• 108091006575 SLC34A3 Proteins 0.000 description 1
• 208000034189 Sclerosis Diseases 0.000 description 1
• 206010040026 Sensory disturbance Diseases 0.000 description 1
• 241000144282 Sigmodon Species 0.000 description 1
• 208000032023 Signs and Symptoms Diseases 0.000 description 1
• 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
• 102000039471 Small Nuclear RNA Human genes 0.000 description 1
• 102000000890 Somatomedin B domains Human genes 0.000 description 1
• 108050007913 Somatomedin B domains Proteins 0.000 description 1
• 102000013275 Somatomedins Human genes 0.000 description 1
• 208000005392 Spasm Diseases 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
• 241000701093 Suid alphaherpesvirus 1 Species 0.000 description 1
• 101150081494 TMPO gene Proteins 0.000 description 1
• 239000004098 Tetracycline Substances 0.000 description 1
• CJEHCEOXPLASCK-MEYUZBJRSA-N Thr-Tyr-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)[C@H](O)C)CC1=CC=C(O)C=C1 CJEHCEOXPLASCK-MEYUZBJRSA-N 0.000 description 1
• 108010022394 Threonine synthase Proteins 0.000 description 1
• 208000007536 Thrombosis Diseases 0.000 description 1
• AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical class IC1=CC(C[C@H](N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-LBPRGKRZSA-N 0.000 description 1
• 206010068872 Toe walking Diseases 0.000 description 1
• 206010044016 Tooth abscess Diseases 0.000 description 1
• 108700009124 Transcription Initiation Site Proteins 0.000 description 1
• 102000004338 Transferrin Human genes 0.000 description 1
• 108090000901 Transferrin Proteins 0.000 description 1
• 108091005956 Type II transmembrane proteins Proteins 0.000 description 1
• 101150008036 UL29 gene Proteins 0.000 description 1
• 101150011902 UL52 gene Proteins 0.000 description 1
• 108090000848 Ubiquitin Proteins 0.000 description 1
• 102000044159 Ubiquitin Human genes 0.000 description 1
• LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 1
• 241000700618 Vaccinia virus Species 0.000 description 1
• BTWMICVCQLKKNR-DCAQKATOSA-N Val-Leu-Ser Chemical compound CC(C)[C@H]([NH3+])C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C([O-])=O BTWMICVCQLKKNR-DCAQKATOSA-N 0.000 description 1
• 201000004810 Vascular dementia Diseases 0.000 description 1
• 108700005077 Viral Genes Proteins 0.000 description 1
• 206010047700 Vomiting Diseases 0.000 description 1
• 238000011892 Von Kossa's method Methods 0.000 description 1
• 210000001015 abdomen Anatomy 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• 230000001133 acceleration Effects 0.000 description 1
• 229960000583 acetic acid Drugs 0.000 description 1
• RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 1
• 108091006088 activator proteins Proteins 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 108700019030 adenovirus E4orf6 Proteins 0.000 description 1
• 210000000577 adipose tissue Anatomy 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 210000005058 airway cell Anatomy 0.000 description 1
• GZCGUPFRVQAUEE-SLPGGIOYSA-N aldehydo-D-glucose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O GZCGUPFRVQAUEE-SLPGGIOYSA-N 0.000 description 1
• RGCKGOZRHPZPFP-UHFFFAOYSA-N alizarin Chemical compound C1=CC=C2C(=O)C3=C(O)C(O)=CC=C3C(=O)C2=C1 RGCKGOZRHPZPFP-UHFFFAOYSA-N 0.000 description 1
• 229940100198 alkylating agent Drugs 0.000 description 1
• 239000002168 alkylating agent Substances 0.000 description 1
• 230000000172 allergic effect Effects 0.000 description 1
• 239000008168 almond oil Substances 0.000 description 1
• 108010091628 alpha 1-Antichymotrypsin Proteins 0.000 description 1
• 108010075843 alpha-2-HS-Glycoprotein Proteins 0.000 description 1
• 102000012005 alpha-2-HS-Glycoprotein Human genes 0.000 description 1
• 108010026331 alpha-Fetoproteins Proteins 0.000 description 1
• 102000013529 alpha-Fetoproteins Human genes 0.000 description 1
• 230000037005 anaesthesia Effects 0.000 description 1
• 208000007502 anemia Diseases 0.000 description 1
• 238000002399 angioplasty Methods 0.000 description 1
• 210000003423 ankle Anatomy 0.000 description 1
• 229940045799 anthracyclines and related substance Drugs 0.000 description 1
• 230000000340 anti-metabolite Effects 0.000 description 1
• 230000003409 anti-rejection Effects 0.000 description 1
• 230000001475 anti-trypsic effect Effects 0.000 description 1
• 229940088710 antibiotic agent Drugs 0.000 description 1
• 229940100197 antimetabolite Drugs 0.000 description 1
• 239000002256 antimetabolite Substances 0.000 description 1
• 229940045687 antimetabolites folic acid analogs Drugs 0.000 description 1
• 229940045719 antineoplastic alkylating agent nitrosoureas Drugs 0.000 description 1
• 239000003972 antineoplastic antibiotic Substances 0.000 description 1
• 229940045688 antineoplastic antimetabolites pyrimidine analogues Drugs 0.000 description 1
• 229940045985 antineoplastic platinum compound Drugs 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 230000036528 appetite Effects 0.000 description 1
• 235000019789 appetite Nutrition 0.000 description 1
• 239000008135 aqueous vehicle Substances 0.000 description 1
• 229940059756 arava Drugs 0.000 description 1
• 206010003246 arthritis Diseases 0.000 description 1
• 208000010668 atopic eczema Diseases 0.000 description 1
• 230000037444 atrophy Effects 0.000 description 1
• 238000000376 autoradiography Methods 0.000 description 1
• 208000037691 autosomal recessive 1 hypophosphatemic rickets Diseases 0.000 description 1
• 210000003719 b-lymphocyte Anatomy 0.000 description 1
• 230000008033 biological extinction Effects 0.000 description 1
• 229960001561 bleomycin Drugs 0.000 description 1
• OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
• 230000036772 blood pressure Effects 0.000 description 1
• 230000037180 bone health Effects 0.000 description 1
• 238000010322 bone marrow transplantation Methods 0.000 description 1
• 230000018678 bone mineralization Effects 0.000 description 1
• 230000010072 bone remodeling Effects 0.000 description 1
• 230000037118 bone strength Effects 0.000 description 1
• 108010006025 bovine growth hormone Proteins 0.000 description 1
• 210000004556 brain Anatomy 0.000 description 1
• 210000000481 breast Anatomy 0.000 description 1
• 239000000337 buffer salt Substances 0.000 description 1
• 210000001217 buttock Anatomy 0.000 description 1
• 235000020964 calcitriol Nutrition 0.000 description 1
• 239000011612 calcitriol Substances 0.000 description 1
• QXDMQSPYEZFLGF-UHFFFAOYSA-L calcium oxalate Chemical class [Ca+2].[O-]C(=O)C([O-])=O QXDMQSPYEZFLGF-UHFFFAOYSA-L 0.000 description 1
• 150000001720 carbohydrates Chemical group 0.000 description 1
• 210000004903 cardiac system Anatomy 0.000 description 1
• 230000007211 cardiovascular event Effects 0.000 description 1
• 210000000748 cardiovascular system Anatomy 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 210000000845 cartilage Anatomy 0.000 description 1
• 238000004113 cell culture Methods 0.000 description 1
• 108091092356 cellular DNA Proteins 0.000 description 1
• 210000003169 central nervous system Anatomy 0.000 description 1
• 238000005119 centrifugation Methods 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 239000003795 chemical substances by application Substances 0.000 description 1
• 229960004630 chlorambucil Drugs 0.000 description 1
• QWJSAWXRUVVRLH-UHFFFAOYSA-M choline bitartrate Chemical compound C[N+](C)(C)CCO.OC(=O)C(O)C(O)C([O-])=O QWJSAWXRUVVRLH-UHFFFAOYSA-M 0.000 description 1
• 229960004874 choline bitartrate Drugs 0.000 description 1
• 210000001612 chondrocyte Anatomy 0.000 description 1
• 238000011210 chromatographic step Methods 0.000 description 1
• 230000001684 chronic effect Effects 0.000 description 1
• 229960001265 ciclosporin Drugs 0.000 description 1
• 208000024980 claudication Diseases 0.000 description 1
• 230000008045 co-localization Effects 0.000 description 1
• 229920001436 collagen Polymers 0.000 description 1
• 238000007398 colorimetric assay Methods 0.000 description 1
• 238000004891 communication Methods 0.000 description 1
• 102000006834 complement receptors Human genes 0.000 description 1
• 108010047295 complement receptors Proteins 0.000 description 1
• 238000013329 compounding Methods 0.000 description 1
• 238000007906 compression Methods 0.000 description 1
• 230000006835 compression Effects 0.000 description 1
• 230000001010 compromised effect Effects 0.000 description 1
• 230000003750 conditioning effect Effects 0.000 description 1
• 239000000994 contrast dye Substances 0.000 description 1
• 239000002872 contrast media Substances 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 239000002285 corn oil Substances 0.000 description 1
• 235000005687 corn oil Nutrition 0.000 description 1
• 210000004087 cornea Anatomy 0.000 description 1
• 230000002596 correlated effect Effects 0.000 description 1
• 230000001054 cortical effect Effects 0.000 description 1
• 229930182912 cyclosporin Natural products 0.000 description 1
• 210000000172 cytosol Anatomy 0.000 description 1
• 229960000640 dactinomycin Drugs 0.000 description 1
• 206010061428 decreased appetite Diseases 0.000 description 1
• 239000007857 degradation product Substances 0.000 description 1
• 230000018044 dehydration Effects 0.000 description 1
• 238000006297 dehydration reaction Methods 0.000 description 1
• 230000003111 delayed effect Effects 0.000 description 1
• 230000002939 deleterious effect Effects 0.000 description 1
• 210000003298 dental enamel Anatomy 0.000 description 1
• CFCUWKMKBJTWLW-UHFFFAOYSA-N deoliosyl-3C-alpha-L-digitoxosyl-MTM Natural products CC=1C(O)=C2C(O)=C3C(=O)C(OC4OC(C)C(O)C(OC5OC(C)C(O)C(OC6OC(C)C(O)C(C)(O)C6)C5)C4)C(C(OC)C(=O)C(O)C(C)O)CC3=CC2=CC=1OC(OC(C)C1O)CC1OC1CC(O)C(O)C(C)O1 CFCUWKMKBJTWLW-UHFFFAOYSA-N 0.000 description 1
• 230000003544 deproteinization Effects 0.000 description 1
• 239000003599 detergent Substances 0.000 description 1
• 229960003957 dexamethasone Drugs 0.000 description 1
• UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
• 206010012601 diabetes mellitus Diseases 0.000 description 1
• 238000003745 diagnosis Methods 0.000 description 1
• 230000000378 dietary effect Effects 0.000 description 1
• 230000029087 digestion Effects 0.000 description 1
• 102000004419 dihydrofolate reductase Human genes 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• 231100000676 disease causative agent Toxicity 0.000 description 1
• 239000002270 dispersing agent Substances 0.000 description 1
• 238000002224 dissection Methods 0.000 description 1
• 230000009429 distress Effects 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 241001493065 dsRNA viruses Species 0.000 description 1
• 230000009977 dual effect Effects 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 230000035194 endochondral ossification Effects 0.000 description 1
• 230000002124 endocrine Effects 0.000 description 1
• 230000007368 endocrine function Effects 0.000 description 1
• 230000002121 endocytic effect Effects 0.000 description 1
• 230000012202 endocytosis Effects 0.000 description 1
• 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 206010014910 enthesopathy Diseases 0.000 description 1
• 210000000981 epithelium Anatomy 0.000 description 1
• 239000003822 epoxy resin Substances 0.000 description 1
• 235000021321 essential mineral Nutrition 0.000 description 1
• 150000002148 esters Chemical class 0.000 description 1
• BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
• 230000003090 exacerbative effect Effects 0.000 description 1
• 239000013613 expression plasmid Substances 0.000 description 1
• 210000002744 extracellular matrix Anatomy 0.000 description 1
• 210000001723 extracellular space Anatomy 0.000 description 1
• 230000002349 favourable effect Effects 0.000 description 1
• 229940012952 fibrinogen Drugs 0.000 description 1
• 230000004761 fibrosis Effects 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 238000001914 filtration Methods 0.000 description 1
• 210000003811 finger Anatomy 0.000 description 1
• 229960002949 fluorouracil Drugs 0.000 description 1
• 150000002224 folic acids Chemical class 0.000 description 1
• 235000012041 food component Nutrition 0.000 description 1
• 210000002683 foot Anatomy 0.000 description 1
• 238000005194 fractionation Methods 0.000 description 1
• 238000013467 fragmentation Methods 0.000 description 1
• 238000006062 fragmentation reaction Methods 0.000 description 1
• 230000037433 frameshift Effects 0.000 description 1
• 239000000417 fungicide Substances 0.000 description 1
• 210000001156 gastric mucosa Anatomy 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 238000012215 gene cloning Methods 0.000 description 1
• 208000016361 genetic disease Diseases 0.000 description 1
• 230000002068 genetic effect Effects 0.000 description 1
• 229940062737 gengraf Drugs 0.000 description 1
• 239000012362 glacial acetic acid Substances 0.000 description 1
• 230000007387 gliosis Effects 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 210000004247 hand Anatomy 0.000 description 1
• 230000035876 healing Effects 0.000 description 1
• 230000003862 health status Effects 0.000 description 1
• 230000010370 hearing loss Effects 0.000 description 1
• 231100000888 hearing loss Toxicity 0.000 description 1
• 208000016354 hearing loss disease Diseases 0.000 description 1
• 210000003709 heart valve Anatomy 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• 208000014951 hematologic disease Diseases 0.000 description 1
• 208000018706 hematopoietic system disease Diseases 0.000 description 1
• 230000000004 hemodynamic effect Effects 0.000 description 1
• 229960002897 heparin Drugs 0.000 description 1
• 229920000669 heparin Polymers 0.000 description 1
• 208000005252 hepatitis A Diseases 0.000 description 1
• 208000002672 hepatitis B Diseases 0.000 description 1
• 230000003284 homeostatic effect Effects 0.000 description 1
• 230000005099 host tropism Effects 0.000 description 1
• 229960000890 hydrocortisone Drugs 0.000 description 1
• 201000005991 hyperphosphatemia Diseases 0.000 description 1
• 208000034783 hypoesthesia Diseases 0.000 description 1
• 229960001680 ibuprofen Drugs 0.000 description 1
• 230000008105 immune reaction Effects 0.000 description 1
• 230000006058 immune tolerance Effects 0.000 description 1
• 230000002163 immunogen Effects 0.000 description 1
• 230000005847 immunogenicity Effects 0.000 description 1
• 229960003444 immunosuppressant agent Drugs 0.000 description 1
• 229940125721 immunosuppressive agent Drugs 0.000 description 1
• 238000002650 immunosuppressive therapy Methods 0.000 description 1
• 239000012535 impurity Substances 0.000 description 1
• 229940073062 imuran Drugs 0.000 description 1
• 238000011503 in vivo imaging Methods 0.000 description 1
• 238000010348 incorporation Methods 0.000 description 1
• 239000000411 inducer Substances 0.000 description 1
• 230000028709 inflammatory response Effects 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 239000003112 inhibitor Substances 0.000 description 1
• 230000002401 inhibitory effect Effects 0.000 description 1
• 238000002743 insertional mutagenesis Methods 0.000 description 1
• 206010022437 insomnia Diseases 0.000 description 1
• 230000010189 intracellular transport Effects 0.000 description 1
• 230000032631 intramembranous ossification Effects 0.000 description 1
• 239000007927 intramuscular injection Substances 0.000 description 1
• 238000010255 intramuscular injection Methods 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• 238000007913 intrathecal administration Methods 0.000 description 1
• 229910052742 iron Inorganic materials 0.000 description 1
• 230000000302 ischemic effect Effects 0.000 description 1
• 229960002725 isoflurane Drugs 0.000 description 1
• 230000007803 itching Effects 0.000 description 1
• 239000000787 lecithin Substances 0.000 description 1
• 229940067606 lecithin Drugs 0.000 description 1
• 235000010445 lecithin Nutrition 0.000 description 1
• 229960000681 leflunomide Drugs 0.000 description 1
• 229940063725 leukeran Drugs 0.000 description 1
• 229960004194 lidocaine Drugs 0.000 description 1
• 238000001638 lipofection Methods 0.000 description 1
• 239000002502 liposome Substances 0.000 description 1
• 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 1
• 210000005229 liver cell Anatomy 0.000 description 1
• 238000011068 loading method Methods 0.000 description 1
• 239000003589 local anesthetic agent Substances 0.000 description 1
• 230000005923 long-lasting effect Effects 0.000 description 1
• 239000006166 lysate Substances 0.000 description 1
• 230000002101 lytic effect Effects 0.000 description 1
• 101710130522 mRNA export factor Proteins 0.000 description 1
• 206010025482 malaise Diseases 0.000 description 1
• 229940035034 maltodextrin Drugs 0.000 description 1
• 239000003550 marker Substances 0.000 description 1
• 239000011159 matrix material Substances 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 1
• 229960001428 mercaptopurine Drugs 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• 230000007102 metabolic function Effects 0.000 description 1
• 230000004060 metabolic process Effects 0.000 description 1
• 230000015689 metaplastic ossification Effects 0.000 description 1
• 230000001394 metastastic effect Effects 0.000 description 1
• 206010061289 metastatic neoplasm Diseases 0.000 description 1
• FFEARJCKVFRZRR-UHFFFAOYSA-N methionine Chemical compound CSCCC(N)C(O)=O FFEARJCKVFRZRR-UHFFFAOYSA-N 0.000 description 1
• 229930182817 methionine Natural products 0.000 description 1
• 235000006109 methionine Nutrition 0.000 description 1
• DWCZIOOZPIDHAB-UHFFFAOYSA-L methyl green Chemical compound [Cl-].[Cl-].C1=CC(N(C)C)=CC=C1C(C=1C=CC(=CC=1)[N+](C)(C)C)=C1C=CC(=[N+](C)C)C=C1 DWCZIOOZPIDHAB-UHFFFAOYSA-L 0.000 description 1
• 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
• 230000003641 microbiacidal effect Effects 0.000 description 1
• 229940124561 microbicide Drugs 0.000 description 1
• 238000000520 microinjection Methods 0.000 description 1
• 230000027939 micturition Effects 0.000 description 1
• CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 description 1
• 230000000116 mitigating effect Effects 0.000 description 1
• 229960004857 mitomycin Drugs 0.000 description 1
• 238000001823 molecular biology technique Methods 0.000 description 1
• 239000000178 monomer Substances 0.000 description 1
• 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
• 235000019796 monopotassium phosphate Nutrition 0.000 description 1
• 230000004973 motor coordination Effects 0.000 description 1
• 210000000663 muscle cell Anatomy 0.000 description 1
• RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 description 1
• 230000037125 natural defense Effects 0.000 description 1
• 229940063121 neoral Drugs 0.000 description 1
• 210000005036 nerve Anatomy 0.000 description 1
• 230000001537 neural effect Effects 0.000 description 1
• 230000007971 neurological deficit Effects 0.000 description 1
• 230000016273 neuron death Effects 0.000 description 1
• 230000007171 neuropathology Effects 0.000 description 1
• 230000003472 neutralizing effect Effects 0.000 description 1
• 229910052757 nitrogen Inorganic materials 0.000 description 1
• 239000002687 nonaqueous vehicle Substances 0.000 description 1
• 230000037434 nonsense mutation Effects 0.000 description 1
• 230000012223 nuclear import Effects 0.000 description 1
• 108010027581 nucleoside triphosphate pyrophosphatase Proteins 0.000 description 1
• 108010067588 nucleotide pyrophosphatase Proteins 0.000 description 1
• 210000004940 nucleus Anatomy 0.000 description 1
• 231100000862 numbness Toxicity 0.000 description 1
• 229910052762 osmium Inorganic materials 0.000 description 1
• SYQBFIAQOQZEGI-UHFFFAOYSA-N osmium atom Chemical compound [Os] SYQBFIAQOQZEGI-UHFFFAOYSA-N 0.000 description 1
• 201000008482 osteoarthritis Diseases 0.000 description 1
• 210000000963 osteoblast Anatomy 0.000 description 1
• 210000002997 osteoclast Anatomy 0.000 description 1
• 230000002188 osteogenic effect Effects 0.000 description 1
• 229940045795 other cytotoxic antibiotic in ATC Drugs 0.000 description 1
• 229940039748 oxalate Drugs 0.000 description 1
• 229940055729 papain Drugs 0.000 description 1
• 235000019834 papain Nutrition 0.000 description 1
• 239000012188 paraffin wax Substances 0.000 description 1
• 229920002866 paraformaldehyde Polymers 0.000 description 1
• 210000002990 parathyroid gland Anatomy 0.000 description 1
• 230000036961 partial effect Effects 0.000 description 1
• 244000052769 pathogen Species 0.000 description 1
• 230000009054 pathological process Effects 0.000 description 1
• 210000004197 pelvis Anatomy 0.000 description 1
• 230000002974 pharmacogenomic effect Effects 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• 150000004713 phosphodiesters Chemical class 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 230000037081 physical activity Effects 0.000 description 1
• 230000003169 placental effect Effects 0.000 description 1
• 150000003058 platinum compounds Chemical class 0.000 description 1
• 229960003171 plicamycin Drugs 0.000 description 1
• 238000013001 point bending Methods 0.000 description 1
• 229920001983 poloxamer Polymers 0.000 description 1
• 229920000647 polyepoxide Polymers 0.000 description 1
• 229920000642 polymer Polymers 0.000 description 1
• 238000006116 polymerization reaction Methods 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
• 229960004618 prednisone Drugs 0.000 description 1
• XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• 230000001902 propagating effect Effects 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
• QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical class CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
• 239000000007 protein synthesis inhibitor Substances 0.000 description 1
• 210000000512 proximal kidney tubule Anatomy 0.000 description 1
• 210000003492 pulmonary vein Anatomy 0.000 description 1
• 230000035485 pulse pressure Effects 0.000 description 1
• 150000003230 pyrimidines Chemical class 0.000 description 1
• 230000001698 pyrogenic effect Effects 0.000 description 1
• 230000005855 radiation Effects 0.000 description 1
• 230000002285 radioactive effect Effects 0.000 description 1
• 239000011535 reaction buffer Substances 0.000 description 1
• 230000006798 recombination Effects 0.000 description 1
• 238000005215 recombination Methods 0.000 description 1
• 239000012926 reference standard material Substances 0.000 description 1
• 101150066583 rep gene Proteins 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 210000002345 respiratory system Anatomy 0.000 description 1
• 108091008146 restriction endonucleases Proteins 0.000 description 1
• 230000002441 reversible effect Effects 0.000 description 1
• 229940061969 rheumatrex Drugs 0.000 description 1
• 238000005070 sampling Methods 0.000 description 1
• 229940063122 sandimmune Drugs 0.000 description 1
• 230000003248 secreting effect Effects 0.000 description 1
• 230000001953 sensory effect Effects 0.000 description 1
• 230000008786 sensory perception of smell Effects 0.000 description 1
• 230000014860 sensory perception of taste Effects 0.000 description 1
• 208000013220 shortness of breath Diseases 0.000 description 1
• 210000004927 skin cell Anatomy 0.000 description 1
• 206010040882 skin lesion Diseases 0.000 description 1
• 231100000444 skin lesion Toxicity 0.000 description 1
• 108091029842 small nuclear ribonucleic acid Proteins 0.000 description 1
• ZNCPFRVNHGOPAG-UHFFFAOYSA-L sodium oxalate Chemical compound [Na+].[Na+].[O-]C(=O)C([O-])=O ZNCPFRVNHGOPAG-UHFFFAOYSA-L 0.000 description 1
• 229940039790 sodium oxalate Drugs 0.000 description 1
• 239000001488 sodium phosphate Substances 0.000 description 1
• 229910000162 sodium phosphate Inorganic materials 0.000 description 1
• 239000002904 solvent Substances 0.000 description 1
• 235000010199 sorbic acid Nutrition 0.000 description 1
• 239000004334 sorbic acid Substances 0.000 description 1
• 229940075582 sorbic acid Drugs 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 235000010356 sorbitol Nutrition 0.000 description 1
• 208000018198 spasticity Diseases 0.000 description 1
• 210000000278 spinal cord Anatomy 0.000 description 1
• 208000020431 spinal cord injury Diseases 0.000 description 1
• 230000002269 spontaneous effect Effects 0.000 description 1
• 238000003153 stable transfection Methods 0.000 description 1
• 150000003431 steroids Chemical class 0.000 description 1
• 210000002784 stomach Anatomy 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 230000009469 supplementation Effects 0.000 description 1
• 230000002459 sustained effect Effects 0.000 description 1
• 239000003826 tablet Substances 0.000 description 1
• 210000002435 tendon Anatomy 0.000 description 1
• 229960002180 tetracycline Drugs 0.000 description 1
• 229930101283 tetracycline Natural products 0.000 description 1
• 235000019364 tetracycline Nutrition 0.000 description 1
• 150000003522 tetracyclines Chemical class 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• 238000004809 thin layer chromatography Methods 0.000 description 1
• 239000005495 thyroid hormone Substances 0.000 description 1
• 229940036555 thyroid hormone Drugs 0.000 description 1
• 238000004448 titration Methods 0.000 description 1
• 210000003371 toe Anatomy 0.000 description 1
• 229950003937 tolonium Drugs 0.000 description 1
• HNONEKILPDHFOL-UHFFFAOYSA-M tolonium chloride Chemical compound [Cl-].C1=C(C)C(N)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 HNONEKILPDHFOL-UHFFFAOYSA-M 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 108091006106 transcriptional activators Proteins 0.000 description 1
• 238000003151 transfection method Methods 0.000 description 1
• 239000012581 transferrin Substances 0.000 description 1
• 108091005703 transmembrane proteins Proteins 0.000 description 1
• 102000035160 transmembrane proteins Human genes 0.000 description 1
• 238000004627 transmission electron microscopy Methods 0.000 description 1
• 238000002054 transplantation Methods 0.000 description 1
• YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
• 239000001226 triphosphate Substances 0.000 description 1
• 235000011178 triphosphate Nutrition 0.000 description 1
• PIEPQKCYPFFYMG-UHFFFAOYSA-N tris acetate Chemical compound CC(O)=O.OCC(N)(CO)CO PIEPQKCYPFFYMG-UHFFFAOYSA-N 0.000 description 1
• RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
• 208000032349 type 2B vitamin D-dependent rickets Diseases 0.000 description 1
• 108010087967 type I signal peptidase Proteins 0.000 description 1
• 238000005199 ultracentrifugation Methods 0.000 description 1
• 241000701447 unidentified baculovirus Species 0.000 description 1
• 238000011144 upstream manufacturing Methods 0.000 description 1
• DNYWZCXLKNTFFI-UHFFFAOYSA-N uranium Chemical compound [U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U][U] DNYWZCXLKNTFFI-UHFFFAOYSA-N 0.000 description 1
• 208000008281 urolithiasis Diseases 0.000 description 1
• 238000002255 vaccination Methods 0.000 description 1
• 229960005486 vaccine Drugs 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 239000008158 vegetable oil Substances 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• 230000035899 viability Effects 0.000 description 1
• 210000003135 vibrissae Anatomy 0.000 description 1
• 230000004095 viral genome expression Effects 0.000 description 1
• 230000029812 viral genome replication Effects 0.000 description 1
• 230000009385 viral infection Effects 0.000 description 1
• 229940088594 vitamin Drugs 0.000 description 1
• 229930003231 vitamin Natural products 0.000 description 1
• 235000013343 vitamin Nutrition 0.000 description 1
• 239000011782 vitamin Substances 0.000 description 1
• 150000003722 vitamin derivatives Chemical class 0.000 description 1
• 230000008673 vomiting Effects 0.000 description 1
• 239000003643 water by type Substances 0.000 description 1
• 239000008215 water for injection Substances 0.000 description 1
• 208000016261 weight loss Diseases 0.000 description 1
• 239000008096 xylene Substances 0.000 description 1
• 239000011592 zinc chloride Substances 0.000 description 1
• 235000005074 zinc chloride Nutrition 0.000 description 1
• JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 1