JP7235702B2 - 核酸生成及び送達のための方法及び製品 - Google Patents
核酸生成及び送達のための方法及び製品 Download PDFInfo
- Publication number
- JP7235702B2 JP7235702B2 JP2020128881A JP2020128881A JP7235702B2 JP 7235702 B2 JP7235702 B2 JP 7235702B2 JP 2020128881 A JP2020128881 A JP 2020128881A JP 2020128881 A JP2020128881 A JP 2020128881A JP 7235702 B2 JP7235702 B2 JP 7235702B2
- Authority
- JP
- Japan
- Prior art keywords
- cells
- protein
- another embodiment
- rna
- nucleic acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 150000007523 nucleic acids Chemical class 0.000 title claims description 236
- 102000039446 nucleic acids Human genes 0.000 title description 233
- 108020004707 nucleic acids Proteins 0.000 title description 233
- 238000000034 method Methods 0.000 title description 170
- 238000012384 transportation and delivery Methods 0.000 title description 38
- 238000004519 manufacturing process Methods 0.000 title description 19
- 108090000623 proteins and genes Proteins 0.000 claims description 269
- 102000004169 proteins and genes Human genes 0.000 claims description 252
- 239000000203 mixture Substances 0.000 claims description 138
- 238000010362 genome editing Methods 0.000 claims description 89
- 230000004568 DNA-binding Effects 0.000 claims description 24
- 238000000338 in vitro Methods 0.000 claims description 23
- 101710163270 Nuclease Proteins 0.000 claims description 22
- -1 meganucleases Proteins 0.000 claims description 22
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 18
- 150000002632 lipids Chemical class 0.000 claims description 18
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 13
- 239000000126 substance Substances 0.000 claims description 12
- 230000008685 targeting Effects 0.000 claims description 11
- 230000005782 double-strand break Effects 0.000 claims description 9
- 101100114361 Arabidopsis thaliana COL7 gene Proteins 0.000 claims description 7
- 108091036407 Polyadenylation Proteins 0.000 claims description 6
- 210000002510 keratinocyte Anatomy 0.000 claims description 5
- 230000005783 single-strand break Effects 0.000 claims description 5
- 102000014914 Carrier Proteins Human genes 0.000 claims description 4
- 108010017070 Zinc Finger Nucleases Proteins 0.000 claims description 4
- 108091008324 binding proteins Proteins 0.000 claims description 4
- 238000010459 TALEN Methods 0.000 claims description 3
- 108010043645 Transcription Activator-Like Effector Nucleases Proteins 0.000 claims description 3
- 108010008532 Deoxyribonuclease I Proteins 0.000 claims description 2
- 102000007260 Deoxyribonuclease I Human genes 0.000 claims description 2
- 108091033409 CRISPR Proteins 0.000 claims 1
- 238000010354 CRISPR gene editing Methods 0.000 claims 1
- 125000003275 alpha amino acid group Chemical group 0.000 claims 1
- 210000004027 cell Anatomy 0.000 description 415
- 235000018102 proteins Nutrition 0.000 description 243
- 229920002477 rna polymer Polymers 0.000 description 229
- 238000001890 transfection Methods 0.000 description 143
- 239000002609 medium Substances 0.000 description 133
- 238000001727 in vivo Methods 0.000 description 107
- 239000002773 nucleotide Substances 0.000 description 86
- 125000003729 nucleotide group Chemical group 0.000 description 86
- 230000008672 reprogramming Effects 0.000 description 80
- 150000001413 amino acids Chemical class 0.000 description 56
- 206010000496 acne Diseases 0.000 description 55
- 208000002874 Acne Vulgaris Diseases 0.000 description 53
- 125000002680 canonical nucleotide group Chemical group 0.000 description 51
- 239000000243 solution Substances 0.000 description 46
- 239000002537 cosmetic Substances 0.000 description 45
- 210000002950 fibroblast Anatomy 0.000 description 45
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 44
- 210000003491 skin Anatomy 0.000 description 43
- 239000012096 transfection reagent Substances 0.000 description 41
- ZAYHVCMSTBRABG-JXOAFFINSA-N 5-methylcytidine Chemical compound O=C1N=C(N)C(C)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 ZAYHVCMSTBRABG-JXOAFFINSA-N 0.000 description 39
- 230000001965 increasing effect Effects 0.000 description 38
- 238000011282 treatment Methods 0.000 description 38
- QXDXBKZJFLRLCM-UAKXSSHOSA-N 5-hydroxyuridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(O)=C1 QXDXBKZJFLRLCM-UAKXSSHOSA-N 0.000 description 37
- 239000003814 drug Substances 0.000 description 36
- NFEXJLMYXXIWPI-JXOAFFINSA-N 5-Hydroxymethylcytidine Chemical compound C1=C(CO)C(N)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NFEXJLMYXXIWPI-JXOAFFINSA-N 0.000 description 35
- 108020004414 DNA Proteins 0.000 description 35
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 34
- JRYMOPZHXMVHTA-DAGMQNCNSA-N 2-amino-7-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1h-pyrrolo[2,3-d]pyrimidin-4-one Chemical compound C1=CC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O JRYMOPZHXMVHTA-DAGMQNCNSA-N 0.000 description 33
- DWRXFEITVBNRMK-JXOAFFINSA-N ribothymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 DWRXFEITVBNRMK-JXOAFFINSA-N 0.000 description 32
- 241001465754 Metazoa Species 0.000 description 29
- ZAYHVCMSTBRABG-UHFFFAOYSA-N 5-Methylcytidine Natural products O=C1N=C(N)C(C)=CN1C1C(O)C(O)C(CO)O1 ZAYHVCMSTBRABG-UHFFFAOYSA-N 0.000 description 28
- 230000027455 binding Effects 0.000 description 28
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 28
- 108091006905 Human Serum Albumin Proteins 0.000 description 27
- 102000008100 Human Serum Albumin Human genes 0.000 description 27
- 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 27
- 238000009472 formulation Methods 0.000 description 27
- 210000001519 tissue Anatomy 0.000 description 27
- 230000035772 mutation Effects 0.000 description 26
- 102100035423 POU domain, class 5, transcription factor 1 Human genes 0.000 description 24
- 238000005516 engineering process Methods 0.000 description 24
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 23
- 101710126211 POU domain, class 5, transcription factor 1 Proteins 0.000 description 23
- 210000004927 skin cell Anatomy 0.000 description 23
- 229940124597 therapeutic agent Drugs 0.000 description 23
- 102000009027 Albumins Human genes 0.000 description 22
- 108010088751 Albumins Proteins 0.000 description 22
- 230000000670 limiting effect Effects 0.000 description 22
- UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 description 21
- 239000012634 fragment Substances 0.000 description 21
- 238000006243 chemical reaction Methods 0.000 description 20
- PTJWIQPHWPFNBW-GBNDHIKLSA-N pseudouridine Chemical group O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1C1=CNC(=O)NC1=O PTJWIQPHWPFNBW-GBNDHIKLSA-N 0.000 description 19
- 238000006467 substitution reaction Methods 0.000 description 19
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 18
- 229960002756 azacitidine Drugs 0.000 description 18
- 230000002500 effect on skin Effects 0.000 description 18
- 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 18
- 238000002347 injection Methods 0.000 description 18
- 239000007924 injection Substances 0.000 description 18
- 230000001225 therapeutic effect Effects 0.000 description 18
- 239000001226 triphosphate Substances 0.000 description 18
- 102000004877 Insulin Human genes 0.000 description 17
- 108090001061 Insulin Proteins 0.000 description 17
- 229930185560 Pseudouridine Natural products 0.000 description 17
- PTJWIQPHWPFNBW-UHFFFAOYSA-N Pseudouridine C Natural products OC1C(O)C(CO)OC1C1=CNC(=O)NC1=O PTJWIQPHWPFNBW-UHFFFAOYSA-N 0.000 description 17
- 108091081062 Repeated sequence (DNA) Proteins 0.000 description 17
- 102000004338 Transferrin Human genes 0.000 description 17
- 108090000901 Transferrin Proteins 0.000 description 17
- WGDUUQDYDIIBKT-UHFFFAOYSA-N beta-Pseudouridine Natural products OC1OC(CN2C=CC(=O)NC2=O)C(O)C1O WGDUUQDYDIIBKT-UHFFFAOYSA-N 0.000 description 17
- 230000014509 gene expression Effects 0.000 description 17
- 239000003018 immunosuppressive agent Substances 0.000 description 17
- 230000001939 inductive effect Effects 0.000 description 17
- 229940125396 insulin Drugs 0.000 description 17
- 231100000419 toxicity Toxicity 0.000 description 17
- 230000001988 toxicity Effects 0.000 description 17
- 238000013518 transcription Methods 0.000 description 17
- 230000035897 transcription Effects 0.000 description 17
- 239000012581 transferrin Substances 0.000 description 17
- 102000008186 Collagen Human genes 0.000 description 16
- 108010035532 Collagen Proteins 0.000 description 16
- 102000053602 DNA Human genes 0.000 description 16
- 102000016942 Elastin Human genes 0.000 description 16
- 108010014258 Elastin Proteins 0.000 description 16
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 16
- 101100247004 Rattus norvegicus Qsox1 gene Proteins 0.000 description 16
- 229920002549 elastin Polymers 0.000 description 16
- 239000002502 liposome Substances 0.000 description 16
- 229940096913 pseudoisocytidine Drugs 0.000 description 16
- 229920001436 collagen Polymers 0.000 description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 15
- MPDKOGQMQLSNOF-GBNDHIKLSA-N 2-amino-5-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1h-pyrimidin-6-one Chemical compound O=C1NC(N)=NC=C1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 MPDKOGQMQLSNOF-GBNDHIKLSA-N 0.000 description 14
- 206010028980 Neoplasm Diseases 0.000 description 14
- 102000003425 Tyrosinase Human genes 0.000 description 14
- 108060008724 Tyrosinase Proteins 0.000 description 14
- 208000024780 Urticaria Diseases 0.000 description 14
- 235000012000 cholesterol Nutrition 0.000 description 14
- 229940107161 cholesterol Drugs 0.000 description 14
- 229960003444 immunosuppressant agent Drugs 0.000 description 14
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 14
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 13
- 108700021430 Kruppel-Like Factor 4 Proteins 0.000 description 13
- 238000010668 complexation reaction Methods 0.000 description 13
- 230000001143 conditioned effect Effects 0.000 description 13
- 238000002474 experimental method Methods 0.000 description 13
- 239000003456 ion exchange resin Substances 0.000 description 13
- 229920003303 ion-exchange polymer Polymers 0.000 description 13
- 210000001778 pluripotent stem cell Anatomy 0.000 description 13
- 235000002639 sodium chloride Nutrition 0.000 description 13
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 12
- OCMSXKMNYAHJMU-JXOAFFINSA-N 4-amino-1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-2-oxopyrimidine-5-carbaldehyde Chemical compound C1=C(C=O)C(N)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 OCMSXKMNYAHJMU-JXOAFFINSA-N 0.000 description 12
- SVRWPYGLQBPNNJ-UAKXSSHOSA-N 4-amino-1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-2-oxopyrimidine-5-carboxylic acid Chemical compound C1=C(C(O)=O)C(N)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 SVRWPYGLQBPNNJ-UAKXSSHOSA-N 0.000 description 12
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 12
- 201000004624 Dermatitis Diseases 0.000 description 12
- LZCNWAXLJWBRJE-ZOQUXTDFSA-N N4-Methylcytidine Chemical compound O=C1N=C(NC)C=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 LZCNWAXLJWBRJE-ZOQUXTDFSA-N 0.000 description 12
- 206010040954 Skin wrinkling Diseases 0.000 description 12
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 12
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 12
- 206010052428 Wound Diseases 0.000 description 12
- 208000027418 Wounds and injury Diseases 0.000 description 12
- BVTBRVFYZUCAKH-UHFFFAOYSA-L disodium selenite Chemical compound [Na+].[Na+].[O-][Se]([O-])=O BVTBRVFYZUCAKH-UHFFFAOYSA-L 0.000 description 12
- 230000008439 repair process Effects 0.000 description 12
- 229960001471 sodium selenite Drugs 0.000 description 12
- 239000011781 sodium selenite Substances 0.000 description 12
- 235000015921 sodium selenite Nutrition 0.000 description 12
- MPPUDRFYDKDPBN-UAKXSSHOSA-N 4-amino-1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-hydroxypyrimidin-2-one Chemical compound C1=C(O)C(N)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 MPPUDRFYDKDPBN-UAKXSSHOSA-N 0.000 description 11
- 239000003153 chemical reaction reagent Substances 0.000 description 11
- 235000014113 dietary fatty acids Nutrition 0.000 description 11
- 201000010099 disease Diseases 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- 229930195729 fatty acid Natural products 0.000 description 11
- 239000000194 fatty acid Substances 0.000 description 11
- 150000004665 fatty acids Chemical class 0.000 description 11
- 108090000765 processed proteins & peptides Proteins 0.000 description 11
- 230000002829 reductive effect Effects 0.000 description 11
- 210000002966 serum Anatomy 0.000 description 11
- 150000003431 steroids Chemical class 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- HITGTSFRKOQULY-DKZDHXMOSA-N 5-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound CC1([C@H]2[C@@H]([C@H](O)[C@@H](CO)O2)O)C=NC(=O)NC1=O HITGTSFRKOQULY-DKZDHXMOSA-N 0.000 description 10
- HJCMDXDYPOUFDY-WHFBIAKZSA-N Ala-Gln Chemical compound C[C@H](N)C(=O)N[C@H](C(O)=O)CCC(N)=O HJCMDXDYPOUFDY-WHFBIAKZSA-N 0.000 description 10
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 description 10
- 102100037362 Fibronectin Human genes 0.000 description 10
- 108010067306 Fibronectins Proteins 0.000 description 10
- 102100021519 Hemoglobin subunit beta Human genes 0.000 description 10
- 108010087705 Proto-Oncogene Proteins c-myc Proteins 0.000 description 10
- 102000009092 Proto-Oncogene Proteins c-myc Human genes 0.000 description 10
- 241000700605 Viruses Species 0.000 description 10
- 239000000556 agonist Substances 0.000 description 10
- 229960002648 alanylglutamine Drugs 0.000 description 10
- 239000002585 base Substances 0.000 description 10
- 230000037303 wrinkles Effects 0.000 description 10
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 9
- 108091026890 Coding region Proteins 0.000 description 9
- 102100027685 Hemoglobin subunit alpha Human genes 0.000 description 9
- 102000013814 Wnt Human genes 0.000 description 9
- 108050003627 Wnt Proteins 0.000 description 9
- 208000010668 atopic eczema Diseases 0.000 description 9
- 201000011510 cancer Diseases 0.000 description 9
- 210000004207 dermis Anatomy 0.000 description 9
- 239000005090 green fluorescent protein Substances 0.000 description 9
- 229960000890 hydrocortisone Drugs 0.000 description 9
- 238000003780 insertion Methods 0.000 description 9
- 230000037431 insertion Effects 0.000 description 9
- 239000011159 matrix material Substances 0.000 description 9
- 239000012528 membrane Substances 0.000 description 9
- 210000001082 somatic cell Anatomy 0.000 description 9
- 235000011178 triphosphate Nutrition 0.000 description 9
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 8
- 108010085238 Actins Proteins 0.000 description 8
- 102000007469 Actins Human genes 0.000 description 8
- 102000012422 Collagen Type I Human genes 0.000 description 8
- 108010022452 Collagen Type I Proteins 0.000 description 8
- 102000029816 Collagenase Human genes 0.000 description 8
- 108060005980 Collagenase Proteins 0.000 description 8
- 101000606090 Homo sapiens Tyrosinase Proteins 0.000 description 8
- 230000009286 beneficial effect Effects 0.000 description 8
- 238000003776 cleavage reaction Methods 0.000 description 8
- 229960002424 collagenase Drugs 0.000 description 8
- 238000012217 deletion Methods 0.000 description 8
- 230000037430 deletion Effects 0.000 description 8
- 230000005684 electric field Effects 0.000 description 8
- 239000003112 inhibitor Substances 0.000 description 8
- 210000004379 membrane Anatomy 0.000 description 8
- 210000000056 organ Anatomy 0.000 description 8
- 150000003230 pyrimidines Chemical class 0.000 description 8
- 150000003839 salts Chemical class 0.000 description 8
- 230000007017 scission Effects 0.000 description 8
- 238000012216 screening Methods 0.000 description 8
- GJTBSTBJLVYKAU-XVFCMESISA-N 2-thiouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=S)NC(=O)C=C1 GJTBSTBJLVYKAU-XVFCMESISA-N 0.000 description 7
- LZWSGWMPCIAGIJ-UAKXSSHOSA-N 4,5-diamino-1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one Chemical compound O=C1N=C(N)C(N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 LZWSGWMPCIAGIJ-UAKXSSHOSA-N 0.000 description 7
- ZLOIGESWDJYCTF-UHFFFAOYSA-N 4-Thiouridine Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=S)C=C1 ZLOIGESWDJYCTF-UHFFFAOYSA-N 0.000 description 7
- ZLOIGESWDJYCTF-XVFCMESISA-N 4-thiouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=S)C=C1 ZLOIGESWDJYCTF-XVFCMESISA-N 0.000 description 7
- 241000699666 Mus <mouse, genus> Species 0.000 description 7
- 239000012124 Opti-MEM Substances 0.000 description 7
- 208000012641 Pigmentation disease Diseases 0.000 description 7
- 201000004681 Psoriasis Diseases 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 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 7
- 239000000872 buffer Substances 0.000 description 7
- 210000000245 forearm Anatomy 0.000 description 7
- 108020001507 fusion proteins Proteins 0.000 description 7
- 102000037865 fusion proteins Human genes 0.000 description 7
- 239000003102 growth factor Substances 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical compound CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 7
- 150000003212 purines Chemical class 0.000 description 7
- BYKRNSHANADUFY-UHFFFAOYSA-M sodium octanoate Chemical compound [Na+].CCCCCCCC([O-])=O BYKRNSHANADUFY-UHFFFAOYSA-M 0.000 description 7
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 7
- 229940045145 uridine Drugs 0.000 description 7
- 239000003981 vehicle Substances 0.000 description 7
- AAAANSSZMCYGTA-UAKXSSHOSA-N 1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-2,4-dioxopyrimidine-5-carboxylic acid Chemical compound OC[C@H]1O[C@H]([C@H](O)[C@@H]1O)n1cc(C(O)=O)c(=O)[nH]c1=O AAAANSSZMCYGTA-UAKXSSHOSA-N 0.000 description 6
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 6
- VQAJJNQKTRZJIQ-JXOAFFINSA-N 5-Hydroxymethyluridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(CO)=C1 VQAJJNQKTRZJIQ-JXOAFFINSA-N 0.000 description 6
- YBTWWWIJBCCYNR-UAKXSSHOSA-N 5-amino-1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 YBTWWWIJBCCYNR-UAKXSSHOSA-N 0.000 description 6
- ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 6
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 6
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 6
- 239000007995 HEPES buffer Substances 0.000 description 6
- 108091005904 Hemoglobin subunit beta Proteins 0.000 description 6
- 101001027128 Homo sapiens Fibronectin Proteins 0.000 description 6
- 101000899111 Homo sapiens Hemoglobin subunit beta Proteins 0.000 description 6
- 102000004889 Interleukin-6 Human genes 0.000 description 6
- 108090001005 Interleukin-6 Proteins 0.000 description 6
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 6
- 108700011259 MicroRNAs Proteins 0.000 description 6
- 230000006819 RNA synthesis Effects 0.000 description 6
- 102100035140 Vitronectin Human genes 0.000 description 6
- 108010031318 Vitronectin Proteins 0.000 description 6
- 201000006083 Xeroderma Pigmentosum Diseases 0.000 description 6
- DLVAMZWIILNQTD-IEKAXWOWSA-H [O-]P([O-])(OC(C(O[C@@H]1[C@H](CO)O)=O)=C1O)=O.[O-]P([O-])(OC(C(O[C@@H]1[C@H](CO)O)=O)=C1O)=O.[O-]P([O-])(OC(C(O[C@@H]1[C@H](CO)O)=O)=C1O)=O.OC[C@@H]([C@H](C(O)=C1OP(O)(O)=O)OC1=O)O.OC[C@@H]([C@H](C(O)=C1OP(O)(O)=O)OC1=O)O.OC[C@@H]([C@H](C(O)=C1OP(O)(O)=O)OC1=O)O.O.O.[Mg+2].[Mg+2].[Mg+2] Chemical compound [O-]P([O-])(OC(C(O[C@@H]1[C@H](CO)O)=O)=C1O)=O.[O-]P([O-])(OC(C(O[C@@H]1[C@H](CO)O)=O)=C1O)=O.[O-]P([O-])(OC(C(O[C@@H]1[C@H](CO)O)=O)=C1O)=O.OC[C@@H]([C@H](C(O)=C1OP(O)(O)=O)OC1=O)O.OC[C@@H]([C@H](C(O)=C1OP(O)(O)=O)OC1=O)O.OC[C@@H]([C@H](C(O)=C1OP(O)(O)=O)OC1=O)O.O.O.[Mg+2].[Mg+2].[Mg+2] DLVAMZWIILNQTD-IEKAXWOWSA-H 0.000 description 6
- 239000003963 antioxidant agent Substances 0.000 description 6
- 235000006708 antioxidants Nutrition 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 230000037319 collagen production Effects 0.000 description 6
- 230000000536 complexating effect Effects 0.000 description 6
- 239000012636 effector Substances 0.000 description 6
- 229940088598 enzyme Drugs 0.000 description 6
- 210000002615 epidermis Anatomy 0.000 description 6
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 6
- 239000008103 glucose Substances 0.000 description 6
- 238000010348 incorporation Methods 0.000 description 6
- 101150111214 lin-28 gene Proteins 0.000 description 6
- 210000004185 liver Anatomy 0.000 description 6
- 239000002679 microRNA Substances 0.000 description 6
- 239000008194 pharmaceutical composition Substances 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 6
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 6
- 229920000053 polysorbate 80 Polymers 0.000 description 6
- 102000004196 processed proteins & peptides Human genes 0.000 description 6
- 210000000130 stem cell Anatomy 0.000 description 6
- 238000002560 therapeutic procedure Methods 0.000 description 6
- 229940042585 tocopherol acetate Drugs 0.000 description 6
- 230000002103 transcriptional effect Effects 0.000 description 6
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 6
- 230000035899 viability Effects 0.000 description 6
- UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 description 5
- RHFUOMFWUGWKKO-XVFCMESISA-N 2-thiocytidine Chemical compound S=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 RHFUOMFWUGWKKO-XVFCMESISA-N 0.000 description 5
- 108020003589 5' Untranslated Regions Proteins 0.000 description 5
- TUZRSOLHFXTHNA-ZEQWWUPGSA-N 5-amino-5-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione Chemical compound NC1([C@H]2[C@@H]([C@H](O)[C@@H](CO)O2)O)C=NC(=O)NC1=O TUZRSOLHFXTHNA-ZEQWWUPGSA-N 0.000 description 5
- 208000030507 AIDS Diseases 0.000 description 5
- 201000004384 Alopecia Diseases 0.000 description 5
- 101150023320 B16R gene Proteins 0.000 description 5
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 5
- 206010053138 Congenital aplastic anaemia Diseases 0.000 description 5
- UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 description 5
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 5
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 5
- 201000004939 Fanconi anemia Diseases 0.000 description 5
- 108091005902 Hemoglobin subunit alpha Proteins 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 5
- NIDVTARKFBZMOT-PEBGCTIMSA-N N(4)-acetylcytidine Chemical compound O=C1N=C(NC(=O)C)C=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NIDVTARKFBZMOT-PEBGCTIMSA-N 0.000 description 5
- 108091023045 Untranslated Region Proteins 0.000 description 5
- 101100316831 Vaccinia virus (strain Copenhagen) B18R gene Proteins 0.000 description 5
- 101100004099 Vaccinia virus (strain Western Reserve) VACWR200 gene Proteins 0.000 description 5
- 230000002411 adverse Effects 0.000 description 5
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 5
- 229960005070 ascorbic acid Drugs 0.000 description 5
- 125000004429 atom Chemical group 0.000 description 5
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 210000000601 blood cell Anatomy 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- 239000006143 cell culture medium Substances 0.000 description 5
- 230000003750 conditioning effect Effects 0.000 description 5
- 229960003957 dexamethasone Drugs 0.000 description 5
- 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 5
- 239000002158 endotoxin Substances 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 230000004927 fusion Effects 0.000 description 5
- 230000002068 genetic effect Effects 0.000 description 5
- 230000036252 glycation Effects 0.000 description 5
- 230000013595 glycosylation Effects 0.000 description 5
- 238000006206 glycosylation reaction Methods 0.000 description 5
- 230000012010 growth Effects 0.000 description 5
- 210000002064 heart cell Anatomy 0.000 description 5
- 208000019622 heart disease Diseases 0.000 description 5
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
- 125000005647 linker group Chemical group 0.000 description 5
- 208000019423 liver disease Diseases 0.000 description 5
- 230000004660 morphological change Effects 0.000 description 5
- RHFUOMFWUGWKKO-UHFFFAOYSA-N s2C Natural products S=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 RHFUOMFWUGWKKO-UHFFFAOYSA-N 0.000 description 5
- 208000007056 sickle cell anemia Diseases 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 150000003408 sphingolipids Chemical class 0.000 description 5
- DUYSYHSSBDVJSM-KRWOKUGFSA-N sphingosine 1-phosphate Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)COP(O)(O)=O DUYSYHSSBDVJSM-KRWOKUGFSA-N 0.000 description 5
- 230000000699 topical effect Effects 0.000 description 5
- 231100000331 toxic Toxicity 0.000 description 5
- 230000002588 toxic effect Effects 0.000 description 5
- KYEKLQMDNZPEFU-KVTDHHQDSA-N 1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,3,5-triazine-2,4-dione Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)N=C1 KYEKLQMDNZPEFU-KVTDHHQDSA-N 0.000 description 4
- UVBYMVOUBXYSFV-XUTVFYLZSA-N 1-methylpseudouridine Chemical compound O=C1NC(=O)N(C)C=C1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 UVBYMVOUBXYSFV-XUTVFYLZSA-N 0.000 description 4
- OTDJAMXESTUWLO-UUOKFMHZSA-N 2-amino-9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)-2-oxolanyl]-3H-purine-6-thione Chemical compound C12=NC(N)=NC(S)=C2N=CN1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OTDJAMXESTUWLO-UUOKFMHZSA-N 0.000 description 4
- NMUSYJAQQFHJEW-UHFFFAOYSA-N 5-Azacytidine Natural products O=C1N=C(N)N=CN1C1C(O)C(O)C(CO)O1 NMUSYJAQQFHJEW-UHFFFAOYSA-N 0.000 description 4
- SKRPUDFNLCXIOY-ZEQWWUPGSA-N 5-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-hydroxypyrimidine-2,4-dione Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1C1(O)C(=O)NC(=O)N=C1 SKRPUDFNLCXIOY-ZEQWWUPGSA-N 0.000 description 4
- BNAWMJKJLNJZFU-GBNDHIKLSA-N 5-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-sulfanylidene-1h-pyrimidin-2-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1C1=CNC(=O)NC1=S BNAWMJKJLNJZFU-GBNDHIKLSA-N 0.000 description 4
- NMUSYJAQQFHJEW-KVTDHHQDSA-N 5-azacytidine Chemical compound O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NMUSYJAQQFHJEW-KVTDHHQDSA-N 0.000 description 4
- CBNRZZNSRJQZNT-IOSLPCCCSA-O 6-thio-7-deaza-guanosine Chemical compound CC1=C[NH+]([C@@H]([C@@H]2O)O[C@H](CO)[C@H]2O)C(NC(N)=N2)=C1C2=S CBNRZZNSRJQZNT-IOSLPCCCSA-O 0.000 description 4
- HDZZVAMISRMYHH-UHFFFAOYSA-N 9beta-Ribofuranosyl-7-deazaadenin Natural products C1=CC=2C(N)=NC=NC=2N1C1OC(CO)C(O)C1O HDZZVAMISRMYHH-UHFFFAOYSA-N 0.000 description 4
- 208000028185 Angioedema Diseases 0.000 description 4
- 208000001454 Anhidrotic Ectodermal Dysplasia 1 Diseases 0.000 description 4
- 206010004146 Basal cell carcinoma Diseases 0.000 description 4
- 206010010452 Congenital ectodermal dysplasia Diseases 0.000 description 4
- MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 4
- 201000003883 Cystic fibrosis Diseases 0.000 description 4
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 4
- 206010013801 Duchenne Muscular Dystrophy Diseases 0.000 description 4
- 206010014989 Epidermolysis bullosa Diseases 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 4
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 4
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 101000851054 Homo sapiens Elastin Proteins 0.000 description 4
- 101001009007 Homo sapiens Hemoglobin subunit alpha Proteins 0.000 description 4
- 208000023105 Huntington disease Diseases 0.000 description 4
- 208000008454 Hyperhidrosis Diseases 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 229930182816 L-glutamine Natural products 0.000 description 4
- 239000012097 Lipofectamine 2000 Substances 0.000 description 4
- 102000015494 Mitochondrial Uncoupling Proteins Human genes 0.000 description 4
- 108010050258 Mitochondrial Uncoupling Proteins Proteins 0.000 description 4
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 4
- 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 4
- VQAYFKKCNSOZKM-IOSLPCCCSA-N N(6)-methyladenosine Chemical compound C1=NC=2C(NC)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O VQAYFKKCNSOZKM-IOSLPCCCSA-N 0.000 description 4
- VQAYFKKCNSOZKM-UHFFFAOYSA-N NSC 29409 Natural products C1=NC=2C(NC)=NC=NC=2N1C1OC(CO)C(O)C1O VQAYFKKCNSOZKM-UHFFFAOYSA-N 0.000 description 4
- 229910019142 PO4 Inorganic materials 0.000 description 4
- 208000018737 Parkinson disease Diseases 0.000 description 4
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- 208000019229 Spleen disease Diseases 0.000 description 4
- 208000002903 Thalassemia Diseases 0.000 description 4
- 108010073062 Transcription Activator-Like Effectors Proteins 0.000 description 4
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 4
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 4
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 4
- 238000000246 agarose gel electrophoresis Methods 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 230000008668 cellular reprogramming Effects 0.000 description 4
- 150000001841 cholesterols Chemical class 0.000 description 4
- 239000002299 complementary DNA Substances 0.000 description 4
- 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 4
- 208000035475 disorder Diseases 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 238000004520 electroporation Methods 0.000 description 4
- 108010026638 endodeoxyribonuclease FokI Proteins 0.000 description 4
- 230000001747 exhibiting effect Effects 0.000 description 4
- 229940126864 fibroblast growth factor Drugs 0.000 description 4
- 229940029575 guanosine Drugs 0.000 description 4
- 230000035876 healing Effects 0.000 description 4
- 102000054289 human ELN Human genes 0.000 description 4
- 201000003535 hypohidrotic ectodermal dysplasia Diseases 0.000 description 4
- 208000035128 hypohidrotic/hair/tooth type autosomal recessive ectodermal dysplasia 10B Diseases 0.000 description 4
- 208000032771 hypohidrotic/hair/tooth type autosomal recessive ectodermal dysplasia 11B Diseases 0.000 description 4
- 206010021198 ichthyosis Diseases 0.000 description 4
- 230000001861 immunosuppressant effect Effects 0.000 description 4
- 230000001976 improved effect Effects 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 150000002500 ions Chemical class 0.000 description 4
- 108020004999 messenger RNA Proteins 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 201000006938 muscular dystrophy Diseases 0.000 description 4
- 239000002777 nucleoside Substances 0.000 description 4
- 230000009437 off-target effect Effects 0.000 description 4
- 125000004430 oxygen atom Chemical group O* 0.000 description 4
- 230000001717 pathogenic effect Effects 0.000 description 4
- 235000021317 phosphate Nutrition 0.000 description 4
- 239000002953 phosphate buffered saline Substances 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 238000007747 plating Methods 0.000 description 4
- 229920001993 poloxamer 188 Polymers 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 102000040430 polynucleotide Human genes 0.000 description 4
- 108091033319 polynucleotide Proteins 0.000 description 4
- 239000002157 polynucleotide Substances 0.000 description 4
- 230000002207 retinal effect Effects 0.000 description 4
- 201000004700 rosacea Diseases 0.000 description 4
- 230000011664 signaling Effects 0.000 description 4
- 238000007390 skin biopsy Methods 0.000 description 4
- 206010041823 squamous cell carcinoma Diseases 0.000 description 4
- 210000000434 stratum corneum Anatomy 0.000 description 4
- 239000004094 surface-active agent Substances 0.000 description 4
- 238000001356 surgical procedure Methods 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 238000011200 topical administration Methods 0.000 description 4
- HDZZVAMISRMYHH-KCGFPETGSA-N tubercidin Chemical compound C1=CC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O HDZZVAMISRMYHH-KCGFPETGSA-N 0.000 description 4
- 239000013598 vector Substances 0.000 description 4
- 239000013603 viral vector Substances 0.000 description 4
- 230000029663 wound healing Effects 0.000 description 4
- 229910052725 zinc Inorganic materials 0.000 description 4
- 239000011701 zinc Substances 0.000 description 4
- MZBPLEJIMYNQQI-JXOAFFINSA-N 1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-2,4-dioxopyrimidine-5-carbaldehyde Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(C=O)=C1 MZBPLEJIMYNQQI-JXOAFFINSA-N 0.000 description 3
- OKTWQKXBJUBAKS-WQADZSDSSA-N 2-[[(e,2r,3s)-2-amino-3-hydroxyoctadec-4-enoxy]-hydroxyphosphoryl]oxyethyl-trimethylazanium;chloride Chemical compound [Cl-].CCCCCCCCCCCCC\C=C\[C@H](O)[C@H](N)COP(O)(=O)OCC[N+](C)(C)C OKTWQKXBJUBAKS-WQADZSDSSA-N 0.000 description 3
- DDHOXEOVAJVODV-GBNDHIKLSA-N 5-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-2-sulfanylidene-1h-pyrimidin-4-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1C1=CNC(=S)NC1=O DDHOXEOVAJVODV-GBNDHIKLSA-N 0.000 description 3
- 208000003911 Acne Keloid Diseases 0.000 description 3
- 208000024827 Alzheimer disease Diseases 0.000 description 3
- 241000271566 Aves Species 0.000 description 3
- 108030001720 Bontoxilysin Proteins 0.000 description 3
- 102100025401 Breast cancer type 1 susceptibility protein Human genes 0.000 description 3
- 102100025399 Breast cancer type 2 susceptibility protein Human genes 0.000 description 3
- 101150023944 CXCR5 gene Proteins 0.000 description 3
- 206010056370 Congestive cardiomyopathy Diseases 0.000 description 3
- 108010079245 Cystic Fibrosis Transmembrane Conductance Regulator Proteins 0.000 description 3
- 102100023419 Cystic fibrosis transmembrane conductance regulator Human genes 0.000 description 3
- 206010012438 Dermatitis atopic Diseases 0.000 description 3
- 206010012442 Dermatitis contact Diseases 0.000 description 3
- 206010051651 Dermatitis papillaris capillitii Diseases 0.000 description 3
- 201000010046 Dilated cardiomyopathy Diseases 0.000 description 3
- 206010013786 Dry skin Diseases 0.000 description 3
- 102100031780 Endonuclease Human genes 0.000 description 3
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 3
- 102100035902 Glutamate decarboxylase 1 Human genes 0.000 description 3
- 102100035857 Glutamate decarboxylase 2 Human genes 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 108010054147 Hemoglobins Proteins 0.000 description 3
- 102000001554 Hemoglobins Human genes 0.000 description 3
- 101000934870 Homo sapiens Breast cancer type 1 susceptibility protein Proteins 0.000 description 3
- 101000934858 Homo sapiens Breast cancer type 2 susceptibility protein Proteins 0.000 description 3
- 101000803709 Homo sapiens Vitronectin Proteins 0.000 description 3
- 102000003918 Hyaluronan Synthases Human genes 0.000 description 3
- 108090000320 Hyaluronan Synthases Proteins 0.000 description 3
- 206010048858 Ischaemic cardiomyopathy Diseases 0.000 description 3
- 239000002211 L-ascorbic acid Substances 0.000 description 3
- 235000000069 L-ascorbic acid Nutrition 0.000 description 3
- 102000004882 Lipase Human genes 0.000 description 3
- 108090001060 Lipase Proteins 0.000 description 3
- 239000004367 Lipase Substances 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 206010027026 Mechanical acne Diseases 0.000 description 3
- 102100034216 Melanocyte-stimulating hormone receptor Human genes 0.000 description 3
- 208000003351 Melanosis Diseases 0.000 description 3
- 102000005741 Metalloproteases Human genes 0.000 description 3
- 108010006035 Metalloproteases Proteins 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- 102220595793 Myc proto-oncogene protein_T58A_mutation Human genes 0.000 description 3
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 3
- 208000035977 Rare disease Diseases 0.000 description 3
- 206010040037 Sensory neuropathy hereditary Diseases 0.000 description 3
- 208000000453 Skin Neoplasms Diseases 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 108010021188 Superoxide Dismutase-1 Proteins 0.000 description 3
- 102100038836 Superoxide dismutase [Cu-Zn] Human genes 0.000 description 3
- 102000046299 Transforming Growth Factor beta1 Human genes 0.000 description 3
- 102000009618 Transforming Growth Factors Human genes 0.000 description 3
- 108010009583 Transforming Growth Factors Proteins 0.000 description 3
- 101800002279 Transforming growth factor beta-1 Proteins 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 108010021428 Type 1 Melanocortin Receptor Proteins 0.000 description 3
- PGAVKCOVUIYSFO-XVFCMESISA-N UTP Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(=O)NC(=O)C=C1 PGAVKCOVUIYSFO-XVFCMESISA-N 0.000 description 3
- 108010021111 Uncoupling Protein 2 Proteins 0.000 description 3
- 102000008219 Uncoupling Protein 2 Human genes 0.000 description 3
- 108010021098 Uncoupling Protein 3 Proteins 0.000 description 3
- 102000008200 Uncoupling Protein 3 Human genes 0.000 description 3
- 101150019524 WNT2 gene Proteins 0.000 description 3
- 102000052547 Wnt-1 Human genes 0.000 description 3
- 108700020987 Wnt-1 Proteins 0.000 description 3
- 102000052556 Wnt-2 Human genes 0.000 description 3
- 108700020986 Wnt-2 Proteins 0.000 description 3
- 102000052549 Wnt-3 Human genes 0.000 description 3
- 108700020985 Wnt-3 Proteins 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 210000001193 acne keloid Anatomy 0.000 description 3
- 210000001789 adipocyte Anatomy 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 3
- 206010068168 androgenetic alopecia Diseases 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 235000010323 ascorbic acid Nutrition 0.000 description 3
- 239000011668 ascorbic acid Substances 0.000 description 3
- 201000008937 atopic dermatitis Diseases 0.000 description 3
- 230000008827 biological function Effects 0.000 description 3
- 230000031018 biological processes and functions Effects 0.000 description 3
- 229940053031 botulinum toxin Drugs 0.000 description 3
- 150000001768 cations Chemical class 0.000 description 3
- 108091092356 cellular DNA Proteins 0.000 description 3
- 238000010276 construction Methods 0.000 description 3
- 238000012258 culturing Methods 0.000 description 3
- 230000017858 demethylation Effects 0.000 description 3
- 238000010520 demethylation reaction Methods 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 230000037336 dry skin Effects 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 230000001815 facial effect Effects 0.000 description 3
- 239000012091 fetal bovine serum Substances 0.000 description 3
- 229960000304 folic acid Drugs 0.000 description 3
- 235000019152 folic acid Nutrition 0.000 description 3
- 239000011724 folic acid Substances 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 210000004209 hair Anatomy 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 208000006454 hepatitis Diseases 0.000 description 3
- 231100000283 hepatitis Toxicity 0.000 description 3
- 208000037584 hereditary sensory and autonomic neuropathy Diseases 0.000 description 3
- 201000006847 hereditary sensory neuropathy Diseases 0.000 description 3
- 150000004679 hydroxides Chemical class 0.000 description 3
- 230000037315 hyperhidrosis Effects 0.000 description 3
- 229940125721 immunosuppressive agent Drugs 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 238000007918 intramuscular administration Methods 0.000 description 3
- 230000000302 ischemic effect Effects 0.000 description 3
- 235000019421 lipase Nutrition 0.000 description 3
- 208000002780 macular degeneration Diseases 0.000 description 3
- 238000012423 maintenance Methods 0.000 description 3
- 230000008099 melanin synthesis Effects 0.000 description 3
- 210000002752 melanocyte Anatomy 0.000 description 3
- 150000004702 methyl esters Chemical class 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 239000007758 minimum essential medium Substances 0.000 description 3
- 210000000663 muscle cell Anatomy 0.000 description 3
- 125000003835 nucleoside group Chemical group 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- 229920001184 polypeptide Polymers 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000003252 repetitive effect Effects 0.000 description 3
- 239000003161 ribonuclease inhibitor Substances 0.000 description 3
- 238000007665 sagging Methods 0.000 description 3
- 208000008742 seborrheic dermatitis Diseases 0.000 description 3
- 201000000849 skin cancer Diseases 0.000 description 3
- XGRLSUFHELJJAB-JGSYTFBMSA-M sodium;[(2r)-2-hydroxy-3-[(z)-octadec-9-enoyl]oxypropyl] hydrogen phosphate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)COP(O)([O-])=O XGRLSUFHELJJAB-JGSYTFBMSA-M 0.000 description 3
- 210000000952 spleen Anatomy 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- PGAVKCOVUIYSFO-UHFFFAOYSA-N uridine-triphosphate Natural products OC1C(O)C(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)OC1N1C(=O)NC(=O)C=C1 PGAVKCOVUIYSFO-UHFFFAOYSA-N 0.000 description 3
- YZOUYRAONFXZSI-SBHWVFSVSA-N (1S,3R,5R,6R,8R,10R,11R,13R,15R,16R,18R,20R,21R,23R,25R,26R,28R,30R,31S,33R,35R,36R,37S,38R,39S,40R,41S,42R,43S,44R,45S,46R,47S,48R,49S)-5,10,15,20,25,30,35-heptakis(hydroxymethyl)-37,39,40,41,42,43,44,45,46,47,48,49-dodecamethoxy-2,4,7,9,12,14,17,19,22,24,27,29,32,34-tetradecaoxaoctacyclo[31.2.2.23,6.28,11.213,16.218,21.223,26.228,31]nonatetracontane-36,38-diol Chemical compound O([C@@H]([C@H]([C@@H]1OC)OC)O[C@H]2[C@@H](O)[C@@H]([C@@H](O[C@@H]3[C@@H](CO)O[C@@H]([C@H]([C@@H]3O)OC)O[C@@H]3[C@@H](CO)O[C@@H]([C@H]([C@@H]3OC)OC)O[C@@H]3[C@@H](CO)O[C@@H]([C@H]([C@@H]3OC)OC)O[C@@H]3[C@@H](CO)O[C@@H]([C@H]([C@@H]3OC)OC)O3)O[C@@H]2CO)OC)[C@H](CO)[C@H]1O[C@@H]1[C@@H](OC)[C@H](OC)[C@H]3[C@@H](CO)O1 YZOUYRAONFXZSI-SBHWVFSVSA-N 0.000 description 2
- QROZCFCNYCVEDO-KQYNXXCUSA-N (2r,3r,4s,5r)-2-[6-(hydroxyamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(NO)=C2N=C1 QROZCFCNYCVEDO-KQYNXXCUSA-N 0.000 description 2
- LVNGJLRDBYCPGB-LDLOPFEMSA-N (R)-1,2-distearoylphosphatidylethanolamine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[NH3+])OC(=O)CCCCCCCCCCCCCCCCC LVNGJLRDBYCPGB-LDLOPFEMSA-N 0.000 description 2
- UVBYMVOUBXYSFV-UHFFFAOYSA-N 1-methylpseudouridine Natural products O=C1NC(=O)N(C)C=C1C1C(O)C(O)C(CO)O1 UVBYMVOUBXYSFV-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- 108020005345 3' Untranslated Regions Proteins 0.000 description 2
- YDGHCPCSMRXRSN-UAKXSSHOSA-N 5-amino-1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-(hydroxyamino)pyrimidin-2-one Chemical compound O=C1N=C(NO)C(N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 YDGHCPCSMRXRSN-UAKXSSHOSA-N 0.000 description 2
- QOVIBFFZCVPCEI-UMMCILCDSA-N 5-amino-3-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6H-triazolo[4,5-d]pyrimidin-7-one Chemical compound N1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O QOVIBFFZCVPCEI-UMMCILCDSA-N 0.000 description 2
- MJJUWOIBPREHRU-MWKIOEHESA-N 7-Deaza-8-azaguanosine Chemical compound NC=1NC(C2=C(N=1)N(N=C2)[C@H]1[C@H](O)[C@H](O)[C@H](O1)CO)=O MJJUWOIBPREHRU-MWKIOEHESA-N 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 2
- 102100034194 Actin-like protein 9 Human genes 0.000 description 2
- 229930024421 Adenine Natural products 0.000 description 2
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 206010002198 Anaphylactic reaction Diseases 0.000 description 2
- 102100032187 Androgen receptor Human genes 0.000 description 2
- 241000272517 Anseriformes Species 0.000 description 2
- 102100021663 Baculoviral IAP repeat-containing protein 5 Human genes 0.000 description 2
- 102100026189 Beta-galactosidase Human genes 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 2
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 description 2
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 2
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 2
- 102100038608 Cathelicidin antimicrobial peptide Human genes 0.000 description 2
- 101710140438 Cathelicidin antimicrobial peptide Proteins 0.000 description 2
- 108010051109 Cell-Penetrating Peptides Proteins 0.000 description 2
- 102000020313 Cell-Penetrating Peptides Human genes 0.000 description 2
- 208000001348 Chloracne Diseases 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- 102000004510 Collagen Type VII Human genes 0.000 description 2
- 108010017377 Collagen Type VII Proteins 0.000 description 2
- 208000035473 Communicable disease Diseases 0.000 description 2
- 229920000858 Cyclodextrin Polymers 0.000 description 2
- 101000636222 Cyprinus carpio Transcriptional regulator Myc-2 Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 102100029766 DNA polymerase theta Human genes 0.000 description 2
- 102100022474 DNA repair protein complementing XP-A cells Human genes 0.000 description 2
- 102100022477 DNA repair protein complementing XP-C cells Human genes 0.000 description 2
- 102000052510 DNA-Binding Proteins Human genes 0.000 description 2
- 206010012468 Dermatitis herpetiformis Diseases 0.000 description 2
- 229920002307 Dextran Polymers 0.000 description 2
- 206010058314 Dysplasia Diseases 0.000 description 2
- 102100024108 Dystrophin Human genes 0.000 description 2
- 206010014190 Eczema asteatotic Diseases 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- 208000010201 Exanthema Diseases 0.000 description 2
- 206010063006 Facial spasm Diseases 0.000 description 2
- 102000009095 Fanconi Anemia Complementation Group A protein Human genes 0.000 description 2
- 108010087740 Fanconi Anemia Complementation Group A protein Proteins 0.000 description 2
- 102100028314 Filaggrin Human genes 0.000 description 2
- 101710088660 Filaggrin Proteins 0.000 description 2
- 206010016936 Folliculitis Diseases 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 102100031885 General transcription and DNA repair factor IIH helicase subunit XPB Human genes 0.000 description 2
- 102100035184 General transcription and DNA repair factor IIH helicase subunit XPD Human genes 0.000 description 2
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 2
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 2
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 2
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 2
- XKMLYUALXHKNFT-UUOKFMHZSA-N Guanosine-5'-triphosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XKMLYUALXHKNFT-UUOKFMHZSA-N 0.000 description 2
- 102100039894 Hemoglobin subunit delta Human genes 0.000 description 2
- 101000799420 Homo sapiens Actin-like protein 9 Proteins 0.000 description 2
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 description 2
- 101100274954 Homo sapiens COL1A1 gene Proteins 0.000 description 2
- 101001094607 Homo sapiens DNA polymerase eta Proteins 0.000 description 2
- 101000865085 Homo sapiens DNA polymerase theta Proteins 0.000 description 2
- 101001053946 Homo sapiens Dystrophin Proteins 0.000 description 2
- 101000920748 Homo sapiens General transcription and DNA repair factor IIH helicase subunit XPB Proteins 0.000 description 2
- 101000873546 Homo sapiens Glutamate decarboxylase 1 Proteins 0.000 description 2
- 101000873786 Homo sapiens Glutamate decarboxylase 2 Proteins 0.000 description 2
- 101001035503 Homo sapiens Hemoglobin subunit delta Proteins 0.000 description 2
- 101000941879 Homo sapiens Leucine-rich repeat serine/threonine-protein kinase 2 Proteins 0.000 description 2
- 101001030211 Homo sapiens Myc proto-oncogene protein Proteins 0.000 description 2
- 101001094700 Homo sapiens POU domain, class 5, transcription factor 1 Proteins 0.000 description 2
- 101000851627 Homo sapiens Transmembrane channel-like protein 6 Proteins 0.000 description 2
- 101000851515 Homo sapiens Transmembrane channel-like protein 8 Proteins 0.000 description 2
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 description 2
- 102000010781 Interleukin-6 Receptors Human genes 0.000 description 2
- 108010038501 Interleukin-6 Receptors Proteins 0.000 description 2
- 102100037792 Interleukin-6 receptor subunit alpha Human genes 0.000 description 2
- 208000002260 Keloid Diseases 0.000 description 2
- MIJPAVRNWPDMOR-ZAFYKAAXSA-N L-ascorbic acid 2-phosphate Chemical compound OC[C@H](O)[C@H]1OC(=O)C(OP(O)(O)=O)=C1O MIJPAVRNWPDMOR-ZAFYKAAXSA-N 0.000 description 2
- 108010085895 Laminin Proteins 0.000 description 2
- 102000007547 Laminin Human genes 0.000 description 2
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 2
- 102100032693 Leucine-rich repeat serine/threonine-protein kinase 2 Human genes 0.000 description 2
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 2
- 239000012098 Lipofectamine RNAiMAX Substances 0.000 description 2
- 102100040406 Lysophosphatidic acid receptor 6 Human genes 0.000 description 2
- 206010068773 Mechanical urticaria Diseases 0.000 description 2
- 201000009053 Neurodermatitis Diseases 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 208000010195 Onychomycosis Diseases 0.000 description 2
- 240000007594 Oryza sativa Species 0.000 description 2
- 235000007164 Oryza sativa Nutrition 0.000 description 2
- 102000004264 Osteopontin Human genes 0.000 description 2
- 108010081689 Osteopontin Proteins 0.000 description 2
- 238000012408 PCR amplification Methods 0.000 description 2
- 206010033733 Papule Diseases 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 229920002873 Polyethylenimine Polymers 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- 108010003894 Protein-Lysine 6-Oxidase Proteins 0.000 description 2
- 102100026858 Protein-lysine 6-oxidase Human genes 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 238000012181 QIAquick gel extraction kit Methods 0.000 description 2
- 239000013614 RNA sample Substances 0.000 description 2
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 2
- 238000011530 RNeasy Mini Kit Methods 0.000 description 2
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- 206010039793 Seborrhoeic dermatitis Diseases 0.000 description 2
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 2
- 102000007562 Serum Albumin Human genes 0.000 description 2
- 108010071390 Serum Albumin Proteins 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 108020004682 Single-Stranded DNA Proteins 0.000 description 2
- 206010040925 Skin striae Diseases 0.000 description 2
- 108020004459 Small interfering RNA Proteins 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 208000004350 Strabismus Diseases 0.000 description 2
- 208000031439 Striae Distensae Diseases 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 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 2
- 108010002687 Survivin Proteins 0.000 description 2
- 101710137500 T7 RNA polymerase Proteins 0.000 description 2
- RZCIEJXAILMSQK-JXOAFFINSA-N TTP Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 RZCIEJXAILMSQK-JXOAFFINSA-N 0.000 description 2
- 108091036066 Three prime untranslated region Proteins 0.000 description 2
- 208000002474 Tinea Diseases 0.000 description 2
- 206010044074 Torticollis Diseases 0.000 description 2
- 102000056172 Transforming growth factor beta-3 Human genes 0.000 description 2
- 108090000097 Transforming growth factor beta-3 Proteins 0.000 description 2
- 102100036810 Transmembrane channel-like protein 6 Human genes 0.000 description 2
- 102100036770 Transmembrane channel-like protein 8 Human genes 0.000 description 2
- 241000893966 Trichophyton verrucosum Species 0.000 description 2
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 2
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 description 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 206010047642 Vitiligo Diseases 0.000 description 2
- 240000008042 Zea mays Species 0.000 description 2
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 2
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 2
- YIJVOACVHQZMKI-JXOAFFINSA-N [[(2r,3s,4r,5r)-5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound O=C1N=C(N)C(C)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 YIJVOACVHQZMKI-JXOAFFINSA-N 0.000 description 2
- NAOOSVVUTFPWHI-JXOAFFINSA-N [[(2r,3s,4r,5r)-5-[4-amino-5-(hydroxymethyl)-2-oxopyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound C1=C(CO)C(N)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 NAOOSVVUTFPWHI-JXOAFFINSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 229960000643 adenine Drugs 0.000 description 2
- 229960005305 adenosine Drugs 0.000 description 2
- 208000002029 allergic contact dermatitis Diseases 0.000 description 2
- 230000000735 allogeneic effect Effects 0.000 description 2
- DTOSIQBPPRVQHS-PDBXOOCHSA-N alpha-linolenic acid Chemical compound CC\C=C/C\C=C/C\C=C/CCCCCCCC(O)=O DTOSIQBPPRVQHS-PDBXOOCHSA-N 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 108010080146 androgen receptors Proteins 0.000 description 2
- 201000002996 androgenic alopecia Diseases 0.000 description 2
- 239000010775 animal oil Substances 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 210000002469 basement membrane Anatomy 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 239000003613 bile acid Substances 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 206010005159 blepharospasm Diseases 0.000 description 2
- 230000000744 blepharospasm Effects 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 229910001424 calcium ion Inorganic materials 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 230000000747 cardiac effect Effects 0.000 description 2
- 210000004413 cardiac myocyte Anatomy 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 201000002866 cervical dystonia Diseases 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 235000012716 cod liver oil Nutrition 0.000 description 2
- 239000003026 cod liver oil Substances 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000003636 conditioned culture medium Substances 0.000 description 2
- 238000011109 contamination Methods 0.000 description 2
- 235000005822 corn Nutrition 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 238000001804 debridement Methods 0.000 description 2
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 238000009795 derivation Methods 0.000 description 2
- 201000000409 dermatographia Diseases 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- 208000002169 ectodermal dysplasia Diseases 0.000 description 2
- 208000031068 ectodermal dysplasia syndrome Diseases 0.000 description 2
- 230000005014 ectopic expression Effects 0.000 description 2
- 108010064033 elastin-binding proteins Proteins 0.000 description 2
- 239000003797 essential amino acid Substances 0.000 description 2
- 235000020776 essential amino acid Nutrition 0.000 description 2
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 2
- 210000003527 eukaryotic cell Anatomy 0.000 description 2
- 201000005884 exanthem Diseases 0.000 description 2
- 208000013603 exercise-induced anaphylaxis Diseases 0.000 description 2
- 210000002744 extracellular matrix Anatomy 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 210000000744 eyelid Anatomy 0.000 description 2
- 230000012953 feeding on blood of other organism Effects 0.000 description 2
- 108060002895 fibrillin Proteins 0.000 description 2
- 102000013370 fibrillin Human genes 0.000 description 2
- 230000003328 fibroblastic effect Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 210000002683 foot Anatomy 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 210000004602 germ cell Anatomy 0.000 description 2
- 239000003862 glucocorticoid Substances 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 208000002557 hidradenitis Diseases 0.000 description 2
- 201000007162 hidradenitis suppurativa Diseases 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
- 201000002597 ichthyosis vulgaris Diseases 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 230000000415 inactivating effect Effects 0.000 description 2
- 230000015788 innate immune response Effects 0.000 description 2
- 210000005007 innate immune system Anatomy 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 108040006858 interleukin-6 receptor activity proteins Proteins 0.000 description 2
- 238000010255 intramuscular injection Methods 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 210000001117 keloid Anatomy 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 229960004194 lidocaine Drugs 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 231100000053 low toxicity Toxicity 0.000 description 2
- 206010025135 lupus erythematosus Diseases 0.000 description 2
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- 229940049920 malate Drugs 0.000 description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 201000001441 melanoma Diseases 0.000 description 2
- 210000002901 mesenchymal stem cell Anatomy 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 150000002739 metals Chemical class 0.000 description 2
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
- 108091070501 miRNA Proteins 0.000 description 2
- 239000000693 micelle Substances 0.000 description 2
- 230000003278 mimic effect Effects 0.000 description 2
- 230000025608 mitochondrion localization Effects 0.000 description 2
- 229960004857 mitomycin Drugs 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 210000003098 myoblast Anatomy 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 210000001577 neostriatum Anatomy 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 230000030648 nucleus localization Effects 0.000 description 2
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 230000003534 oscillatory effect Effects 0.000 description 2
- FIKAKWIAUPDISJ-UHFFFAOYSA-L paraquat dichloride Chemical compound [Cl-].[Cl-].C1=C[N+](C)=CC=C1C1=CC=[N+](C)C=C1 FIKAKWIAUPDISJ-UHFFFAOYSA-L 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 229940124531 pharmaceutical excipient Drugs 0.000 description 2
- 230000008832 photodamage Effects 0.000 description 2
- 230000019612 pigmentation Effects 0.000 description 2
- 229920001992 poloxamer 407 Polymers 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 108020001580 protein domains Proteins 0.000 description 2
- 238000007388 punch biopsy Methods 0.000 description 2
- XKMLYUALXHKNFT-UHFFFAOYSA-N rGTP Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O XKMLYUALXHKNFT-UHFFFAOYSA-N 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 206010037844 rash Diseases 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 231100000916 relative toxicity Toxicity 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 210000000844 retinal pigment epithelial cell Anatomy 0.000 description 2
- 235000009566 rice Nutrition 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 2
- 229940082569 selenite Drugs 0.000 description 2
- MCAHWIHFGHIESP-UHFFFAOYSA-L selenite(2-) Chemical compound [O-][Se]([O-])=O MCAHWIHFGHIESP-UHFFFAOYSA-L 0.000 description 2
- 229910052711 selenium Inorganic materials 0.000 description 2
- 239000011669 selenium Substances 0.000 description 2
- 229940091258 selenium supplement Drugs 0.000 description 2
- 210000002027 skeletal muscle Anatomy 0.000 description 2
- 208000017520 skin disease Diseases 0.000 description 2
- 208000027140 splenic disease Diseases 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 230000035882 stress Effects 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
- 201000005882 tinea unguium Diseases 0.000 description 2
- 230000017423 tissue regeneration Effects 0.000 description 2
- 239000003053 toxin Substances 0.000 description 2
- 231100000765 toxin Toxicity 0.000 description 2
- 108700012359 toxins Proteins 0.000 description 2
- 230000037317 transdermal delivery Effects 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- 230000014616 translation Effects 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- GXFZCDMWGMFGFL-KKXMJGKMSA-N (+)-Tubocurarine chloride hydrochloride Chemical compound [Cl-].[Cl-].C([C@H]1[N+](C)(C)CCC=2C=C(C(=C(OC3=CC=C(C=C3)C[C@H]3C=4C=C(C(=CC=4CC[NH+]3C)OC)O3)C=21)O)OC)C1=CC=C(O)C3=C1 GXFZCDMWGMFGFL-KKXMJGKMSA-N 0.000 description 1
- WVXOMPRLWLXFAP-KQOPCUSDSA-N (25R)-3beta-hydroxycholest-5-en-26-oic acid Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@@H](CCC[C@@H](C)C(O)=O)C)[C@@]1(C)CC2 WVXOMPRLWLXFAP-KQOPCUSDSA-N 0.000 description 1
- IMEBVVPYOVUBKA-UUOKFMHZSA-N (2R,3R,4S,5R)-2-[7-(hydroxyamino)triazolo[4,5-d]pyrimidin-3-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound OC[C@H]1O[C@H]([C@H](O)[C@@H]1O)n1nnc2c(NO)ncnc12 IMEBVVPYOVUBKA-UUOKFMHZSA-N 0.000 description 1
- DGKZTAGCCXJUAT-KQYNXXCUSA-N (2r,3r,4s,5r)-2-(6-hydrazinylpurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(NN)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O DGKZTAGCCXJUAT-KQYNXXCUSA-N 0.000 description 1
- KLNYEFMNJOUCTO-UUOKFMHZSA-N (2r,3r,4s,5r)-2-(7-hydrazinyltriazolo[4,5-d]pyrimidin-3-yl)-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound N1=NC=2C(NN)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O KLNYEFMNJOUCTO-UUOKFMHZSA-N 0.000 description 1
- IFCGNCLEKGDBDJ-KQYNXXCUSA-N (2r,3s,4r,5r)-2-(hydroxymethyl)-5-[7-(methylamino)triazolo[4,5-d]pyrimidin-3-yl]oxolane-3,4-diol Chemical compound N1=NC=2C(NC)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O IFCGNCLEKGDBDJ-KQYNXXCUSA-N 0.000 description 1
- RUDATBOHQWOJDD-UHFFFAOYSA-N (3beta,5beta,7alpha)-3,7-Dihydroxycholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 RUDATBOHQWOJDD-UHFFFAOYSA-N 0.000 description 1
- CCEITODEOHVTFL-DBRKOABJSA-N (4Z)-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydrazinylidene-5-methyl-1,3,5-triazinan-2-one Chemical compound CN1CN([C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)C(=O)N=C1NN CCEITODEOHVTFL-DBRKOABJSA-N 0.000 description 1
- COZFVHUNJZMFQL-BDVVBNJOSA-N (6r)-6-[(8r,9s,10s,13r,14s,17r)-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylheptanoic acid Chemical compound C1CC2CCCC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@@H](CCCC(C)C(O)=O)C)[C@@]1(C)CC2 COZFVHUNJZMFQL-BDVVBNJOSA-N 0.000 description 1
- OYHQOLUKZRVURQ-NTGFUMLPSA-N (9Z,12Z)-9,10,12,13-tetratritiooctadeca-9,12-dienoic acid Chemical compound C(CCCCCCC\C(=C(/C\C(=C(/CCCCC)\[3H])\[3H])\[3H])\[3H])(=O)O OYHQOLUKZRVURQ-NTGFUMLPSA-N 0.000 description 1
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 1
- ABGLXZLYLBSFDZ-KVTDHHQDSA-N 1,6-diamino-3-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-2h-1,3,5-triazin-4-one Chemical compound O=C1N=C(N)N(N)CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 ABGLXZLYLBSFDZ-KVTDHHQDSA-N 0.000 description 1
- ODDDVFDZBGTKDX-VPCXQMTMSA-N 1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)-2-methyloxolan-2-yl]pyrimidine-2,4-dione Chemical group C1=CC(=O)NC(=O)N1[C@]1(C)O[C@H](CO)[C@@H](O)[C@H]1O ODDDVFDZBGTKDX-VPCXQMTMSA-N 0.000 description 1
- ARYVNLRUDOYCGR-KVTDHHQDSA-N 1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-(hydroxyamino)-1,3,5-triazin-2-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)N=C(NO)N=C1 ARYVNLRUDOYCGR-KVTDHHQDSA-N 0.000 description 1
- FIAQJMSWEWAREU-JXOAFFINSA-N 1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-(hydroxyamino)-5-methylpyrimidin-2-one Chemical compound O=C1N=C(NO)C(C)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 FIAQJMSWEWAREU-JXOAFFINSA-N 0.000 description 1
- WVMPZTYBROSQRJ-DBRKOABJSA-N 1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-(methylamino)-1,3,5-triazin-2-one Chemical compound O=C1N=C(NC)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 WVMPZTYBROSQRJ-DBRKOABJSA-N 0.000 description 1
- OQDGQWRCJQEJRX-KVTDHHQDSA-N 1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydrazinyl-1,3,5-triazin-2-one Chemical compound O=C1N=C(NN)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 OQDGQWRCJQEJRX-KVTDHHQDSA-N 0.000 description 1
- MHOFECSHUOJTRF-UAKXSSHOSA-N 1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydrazinyl-5-hydroxypyrimidin-2-one Chemical compound C1=C(O)C(NN)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 MHOFECSHUOJTRF-UAKXSSHOSA-N 0.000 description 1
- YUNJBQDCTLSQCZ-JXOAFFINSA-N 1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydrazinyl-5-methylpyrimidin-2-one Chemical compound O=C1N=C(NN)C(C)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 YUNJBQDCTLSQCZ-JXOAFFINSA-N 0.000 description 1
- RSSRMDMJEZIUJX-XVFCMESISA-N 1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydrazinylpyrimidin-2-one Chemical compound O=C1N=C(NN)C=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 RSSRMDMJEZIUJX-XVFCMESISA-N 0.000 description 1
- RNKDWPJBJIFTKV-KVTDHHQDSA-N 1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-hydroxy-1,3,5-triazinane-2,4-dione Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)N(O)C1 RNKDWPJBJIFTKV-KVTDHHQDSA-N 0.000 description 1
- UXCALUXXUFSTBY-UAKXSSHOSA-N 1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-hydroxy-4-(hydroxyamino)pyrimidin-2-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)N=C(NO)C(O)=C1 UXCALUXXUFSTBY-UAKXSSHOSA-N 0.000 description 1
- LKBQDNUCHULBBA-JXOAFFINSA-N 1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-hydroxy-4-(methylamino)pyrimidin-2-one Chemical compound C1=C(O)C(NC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 LKBQDNUCHULBBA-JXOAFFINSA-N 0.000 description 1
- FQLVAQCZHLHEIP-DBRKOABJSA-N 1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-1,3,5-triazinane-2,4-dione Chemical compound O=C1NC(=O)N(C)CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 FQLVAQCZHLHEIP-DBRKOABJSA-N 0.000 description 1
- QJFQWYBWIIJENY-FDDDBJFASA-N 1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-4-(methylamino)pyrimidin-2-one Chemical compound C1=C(C)C(NC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 QJFQWYBWIIJENY-FDDDBJFASA-N 0.000 description 1
- WOWKPCXEBJGZMT-KVTDHHQDSA-N 1-amino-3-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-(hydroxyamino)-2h-1,3,5-triazin-4-one Chemical compound O=C1N=C(NO)N(N)CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 WOWKPCXEBJGZMT-KVTDHHQDSA-N 0.000 description 1
- KKNOZXSBLXTZCI-DBRKOABJSA-N 1-amino-3-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-(methylamino)-2h-1,3,5-triazin-4-one Chemical compound C1N(N)C(NC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 KKNOZXSBLXTZCI-DBRKOABJSA-N 0.000 description 1
- CNDJSOTUEUHZDN-KVTDHHQDSA-N 1-amino-3-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-hydrazinyl-2h-1,3,5-triazin-4-one Chemical compound C1N(N)C(NN)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 CNDJSOTUEUHZDN-KVTDHHQDSA-N 0.000 description 1
- YIBJSENXVGMWRM-KVTDHHQDSA-N 1-amino-5-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,3,5-triazinane-2,4-dione Chemical compound O=C1NC(=O)N(N)CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 YIBJSENXVGMWRM-KVTDHHQDSA-N 0.000 description 1
- 101800001779 2'-O-methyltransferase Proteins 0.000 description 1
- RUVFIDKLDALOGA-UHFFFAOYSA-N 2,2-dihydroxybutanedioic acid Chemical compound OC(=O)CC(O)(O)C(O)=O RUVFIDKLDALOGA-UHFFFAOYSA-N 0.000 description 1
- HCSBTDBGTNZOAB-UHFFFAOYSA-N 2,3-dinitrobenzoic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1[N+]([O-])=O HCSBTDBGTNZOAB-UHFFFAOYSA-N 0.000 description 1
- WXTMDXOMEHJXQO-UHFFFAOYSA-N 2,5-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC(O)=CC=C1O WXTMDXOMEHJXQO-UHFFFAOYSA-N 0.000 description 1
- MMKZAICYSVWBPW-UHFFFAOYSA-N 2-[[2-(difluoromethoxy)phenyl]methylamino]-1-[3-(trifluoromethyl)phenyl]ethanol Chemical compound C=1C=CC(C(F)(F)F)=CC=1C(O)CNCC1=CC=CC=C1OC(F)F MMKZAICYSVWBPW-UHFFFAOYSA-N 0.000 description 1
- AFENDNXGAFYKQO-UHFFFAOYSA-N 2-hydroxybutyric acid Chemical compound CCC(O)C(O)=O AFENDNXGAFYKQO-UHFFFAOYSA-N 0.000 description 1
- IVHKZCSZELZKSJ-UHFFFAOYSA-N 2-hydroxyethyl sulfonate Chemical compound OCCOS(=O)=O IVHKZCSZELZKSJ-UHFFFAOYSA-N 0.000 description 1
- HMGCGUWFPZVPEK-UHFFFAOYSA-N 2-naphthalen-2-ylbenzoic acid Chemical compound OC(=O)C1=CC=CC=C1C1=CC=C(C=CC=C2)C2=C1 HMGCGUWFPZVPEK-UHFFFAOYSA-N 0.000 description 1
- DXEJZRDJXRVUPN-XUTVFYLZSA-N 3-Methylpseudouridine Chemical compound O=C1N(C)C(=O)NC=C1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 DXEJZRDJXRVUPN-XUTVFYLZSA-N 0.000 description 1
- IYPBDMKBQJGCLT-KVTDHHQDSA-N 3-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1-hydroxy-6-(hydroxyamino)-2h-1,3,5-triazin-4-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)N=C(NO)N(O)C1 IYPBDMKBQJGCLT-KVTDHHQDSA-N 0.000 description 1
- HHAAQEZYQXNVDN-DBRKOABJSA-N 3-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1-hydroxy-6-(methylamino)-2h-1,3,5-triazin-4-one Chemical compound C1N(O)C(NC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 HHAAQEZYQXNVDN-DBRKOABJSA-N 0.000 description 1
- LWOXGYIDLHBWQL-WCTZXXKLSA-N 3-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1-methyl-6-(methylamino)-2h-1,3,5-triazin-4-one Chemical compound C1N(C)C(NC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 LWOXGYIDLHBWQL-WCTZXXKLSA-N 0.000 description 1
- FFJZTSHFIURSSU-DBRKOABJSA-N 3-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-(hydroxyamino)-1-methyl-2h-1,3,5-triazin-4-one Chemical compound O=C1N=C(NO)N(C)CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 FFJZTSHFIURSSU-DBRKOABJSA-N 0.000 description 1
- AVRXOMHHZIEGHW-KVTDHHQDSA-N 3-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-hydrazinyl-1-hydroxy-2h-1,3,5-triazin-4-one Chemical compound C1N(O)C(NN)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 AVRXOMHHZIEGHW-KVTDHHQDSA-N 0.000 description 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
- QZLXABHECFKNLT-UAKXSSHOSA-N 4-amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[[hydroxy-[hydroxy(phosphonooxy)phosphoryl]oxyphosphoryl]oxymethyl]oxolan-2-yl]-2-oxopyrimidine-5-carboxylic acid Chemical compound C1=C(C(O)=O)C(N)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 QZLXABHECFKNLT-UAKXSSHOSA-N 0.000 description 1
- VOEJKTLBNFDGGT-JXOAFFINSA-N 4-amino-1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-(methylamino)pyrimidin-2-one Chemical compound O=C1N=C(N)C(NC)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 VOEJKTLBNFDGGT-JXOAFFINSA-N 0.000 description 1
- UEHXEKJKNOHULW-FDDDBJFASA-N 4-amino-1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-ethylpyrimidin-2-one Chemical compound O=C1N=C(N)C(CC)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 UEHXEKJKNOHULW-FDDDBJFASA-N 0.000 description 1
- OZHIJZYBTCTDQC-JXOAFFINSA-N 4-amino-1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2-thione Chemical compound S=C1N=C(N)C(C)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 OZHIJZYBTCTDQC-JXOAFFINSA-N 0.000 description 1
- NGCMLYZVLNLYTA-UAKXSSHOSA-N 4-amino-1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-nitropyrimidin-2-one Chemical compound C1=C([N+]([O-])=O)C(N)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NGCMLYZVLNLYTA-UAKXSSHOSA-N 0.000 description 1
- PXACTUVBBMDKRW-UHFFFAOYSA-N 4-bromobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(Br)C=C1 PXACTUVBBMDKRW-UHFFFAOYSA-N 0.000 description 1
- OBKXEAXTFZPCHS-UHFFFAOYSA-N 4-phenylbutyric acid Chemical compound OC(=O)CCCC1=CC=CC=C1 OBKXEAXTFZPCHS-UHFFFAOYSA-N 0.000 description 1
- DXEJZRDJXRVUPN-UHFFFAOYSA-N 5-[3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-3-methyl-1h-pyrimidine-2,4-dione Chemical compound O=C1N(C)C(=O)NC=C1C1C(O)C(O)C(CO)O1 DXEJZRDJXRVUPN-UHFFFAOYSA-N 0.000 description 1
- PRZPQRIVPUNQTO-JXOAFFINSA-N 5-amino-1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-(methylamino)pyrimidin-2-one Chemical compound C1=C(N)C(NC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 PRZPQRIVPUNQTO-JXOAFFINSA-N 0.000 description 1
- PXAVPJLBJSKTBJ-UAKXSSHOSA-N 5-amino-1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydrazinylpyrimidin-2-one Chemical compound C1=C(N)C(NN)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 PXAVPJLBJSKTBJ-UAKXSSHOSA-N 0.000 description 1
- GEHRSERUQRFUFW-UHFFFAOYSA-N 5-ethylhex-2-ynedioic acid Chemical compound CCC(C(O)=O)CC#CC(O)=O GEHRSERUQRFUFW-UHFFFAOYSA-N 0.000 description 1
- OZTOEARQSSIFOG-MWKIOEHESA-N 6-Thio-7-deaza-8-azaguanosine Chemical compound Nc1nc(=S)c2cnn([C@@H]3O[C@H](CO)[C@@H](O)[C@H]3O)c2[nH]1 OZTOEARQSSIFOG-MWKIOEHESA-N 0.000 description 1
- PRKXZPRMTSMQEP-KVTDHHQDSA-N 6-amino-3-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1-hydroxy-2h-1,3,5-triazin-4-one Chemical compound C1N(O)C(N)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 PRKXZPRMTSMQEP-KVTDHHQDSA-N 0.000 description 1
- OHMBAVJOBLEQPZ-DBRKOABJSA-N 6-amino-3-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1-methyl-2h-1,3,5-triazin-4-one Chemical compound O=C1N=C(N)N(C)CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 OHMBAVJOBLEQPZ-DBRKOABJSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- OAUKGFJQZRGECT-UUOKFMHZSA-N 8-Azaadenosine Chemical compound N1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OAUKGFJQZRGECT-UUOKFMHZSA-N 0.000 description 1
- ZKRFOXLVOKTUTA-KQYNXXCUSA-N 9-(5-phosphoribofuranosyl)-6-mercaptopurine Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(O)=O)O[C@H]1N1C(NC=NC2=S)=C2N=C1 ZKRFOXLVOKTUTA-KQYNXXCUSA-N 0.000 description 1
- 108010029988 AICDA (activation-induced cytidine deaminase) Proteins 0.000 description 1
- 101150037123 APOE gene Proteins 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 235000006491 Acacia senegal Nutrition 0.000 description 1
- 206010058820 Acantholysis Diseases 0.000 description 1
- 206010063409 Acarodermatitis Diseases 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000002782 Acneiform Eruptions Diseases 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- 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 1
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 1
- 208000010370 Adenoviridae Infections Diseases 0.000 description 1
- 206010060931 Adenovirus infection Diseases 0.000 description 1
- 102100021333 Alpha-(1,3)-fucosyltransferase 7 Human genes 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 208000024985 Alport syndrome Diseases 0.000 description 1
- 108010001781 Apligraf Proteins 0.000 description 1
- 102100029470 Apolipoprotein E Human genes 0.000 description 1
- 101100328883 Arabidopsis thaliana COL1 gene Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 206010003399 Arthropod bite Diseases 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 101150115284 BIRC5 gene Proteins 0.000 description 1
- 108700020462 BRCA2 Proteins 0.000 description 1
- 102000052609 BRCA2 Human genes 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010062804 Basal cell naevus syndrome Diseases 0.000 description 1
- 206010004265 Benign familial pemphigus Diseases 0.000 description 1
- 208000003014 Bites and Stings Diseases 0.000 description 1
- 108010049955 Bone Morphogenetic Protein 4 Proteins 0.000 description 1
- 102100024505 Bone morphogenetic protein 4 Human genes 0.000 description 1
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 description 1
- 101710149870 C-C chemokine receptor type 5 Proteins 0.000 description 1
- 101150077194 CAP1 gene Proteins 0.000 description 1
- 101150014715 CAP2 gene Proteins 0.000 description 1
- 101150017501 CCR5 gene Proteins 0.000 description 1
- 108050006947 CXC Chemokine Proteins 0.000 description 1
- 102000019388 CXC chemokine Human genes 0.000 description 1
- 108090000312 Calcium Channels Proteins 0.000 description 1
- 102000003922 Calcium Channels Human genes 0.000 description 1
- 208000003643 Callosities Diseases 0.000 description 1
- 206010007134 Candida infections Diseases 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 239000005632 Capric acid (CAS 334-48-5) Substances 0.000 description 1
- 206010048610 Cardiotoxicity Diseases 0.000 description 1
- 208000002177 Cataract Diseases 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 206010007882 Cellulitis Diseases 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 208000008964 Chemical and Drug Induced Liver Injury Diseases 0.000 description 1
- 208000010445 Chilblains Diseases 0.000 description 1
- 206010008528 Chillblains Diseases 0.000 description 1
- 206010008570 Chloasma Diseases 0.000 description 1
- 108010062745 Chloride Channels Proteins 0.000 description 1
- 102000011045 Chloride Channels Human genes 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 101710164760 Chlorotoxin Proteins 0.000 description 1
- 241001111317 Chondrodendron tomentosum Species 0.000 description 1
- 108010077544 Chromatin Proteins 0.000 description 1
- 206010008805 Chromosomal abnormalities Diseases 0.000 description 1
- 208000031404 Chromosome Aberrations Diseases 0.000 description 1
- 208000032544 Cicatrix Diseases 0.000 description 1
- 102000001187 Collagen Type III Human genes 0.000 description 1
- 108010069502 Collagen Type III Proteins 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 206010052465 Congenital poikiloderma Diseases 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 208000034656 Contusions Diseases 0.000 description 1
- 239000008709 Curare Substances 0.000 description 1
- PCDQPRRSZKQHHS-CCXZUQQUSA-N Cytarabine Triphosphate Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 PCDQPRRSZKQHHS-CCXZUQQUSA-N 0.000 description 1
- PCDQPRRSZKQHHS-UHFFFAOYSA-N Cytidine 5'-triphosphate Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 PCDQPRRSZKQHHS-UHFFFAOYSA-N 0.000 description 1
- 206010011831 Cytomegalovirus infection Diseases 0.000 description 1
- DSLZVSRJTYRBFB-LLEIAEIESA-N D-glucaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O DSLZVSRJTYRBFB-LLEIAEIESA-N 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- 102100031867 DNA excision repair protein ERCC-6 Human genes 0.000 description 1
- 108700020911 DNA-Binding Proteins Proteins 0.000 description 1
- 101710096438 DNA-binding protein Proteins 0.000 description 1
- XULFJDKZVHTRLG-JDVCJPALSA-N DOSPA trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.CCCCCCCC\C=C/CCCCCCCCOCC(C[N+](C)(C)CCNC(=O)C(CCCNCCCN)NCCCN)OCCCCCCCC\C=C/CCCCCCCC XULFJDKZVHTRLG-JDVCJPALSA-N 0.000 description 1
- 108010019673 Darbepoetin alfa Proteins 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 206010012432 Dermatitis acneiform Diseases 0.000 description 1
- 206010012444 Dermatitis diaper Diseases 0.000 description 1
- 206010012455 Dermatitis exfoliative Diseases 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 208000003105 Diaper Rash Diseases 0.000 description 1
- 101001139158 Dictyostelium discoideum Kinesin-related protein 3 Proteins 0.000 description 1
- 101100226017 Dictyostelium discoideum repD gene Proteins 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- 206010072268 Drug-induced liver injury Diseases 0.000 description 1
- 208000005373 Dyshidrotic Eczema Diseases 0.000 description 1
- 108010069091 Dystrophin Proteins 0.000 description 1
- 102000001039 Dystrophin Human genes 0.000 description 1
- 101150105460 ERCC2 gene Proteins 0.000 description 1
- 208000002197 Ehlers-Danlos syndrome Diseases 0.000 description 1
- 208000029497 Elastoma Diseases 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 206010014970 Ephelides Diseases 0.000 description 1
- 102400001368 Epidermal growth factor Human genes 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- 206010015108 Epstein-Barr virus infection Diseases 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 206010015226 Erythema nodosum Diseases 0.000 description 1
- 102000003951 Erythropoietin Human genes 0.000 description 1
- 108090000394 Erythropoietin Proteins 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 108091029865 Exogenous DNA Proteins 0.000 description 1
- 208000037574 Familial benign chronic pemphigus Diseases 0.000 description 1
- 102100034552 Fanconi anemia group M protein Human genes 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 102100028071 Fibroblast growth factor 7 Human genes 0.000 description 1
- 108090000385 Fibroblast growth factor 7 Proteins 0.000 description 1
- 108700041153 Filaggrin Proteins Proteins 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- 208000022072 Gallbladder Neoplasms Diseases 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 206010017711 Gangrene Diseases 0.000 description 1
- 208000031448 Genomic Instability Diseases 0.000 description 1
- 208000009139 Gilbert Disease Diseases 0.000 description 1
- 208000022412 Gilbert syndrome Diseases 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 208000031995 Gorlin syndrome Diseases 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 206010018852 Haematoma Diseases 0.000 description 1
- 208000027655 Hailey-Hailey disease Diseases 0.000 description 1
- 208000004095 Hemifacial Spasm Diseases 0.000 description 1
- 208000018565 Hemochromatosis Diseases 0.000 description 1
- 208000002972 Hepatolenticular Degeneration Diseases 0.000 description 1
- 206010019851 Hepatotoxicity Diseases 0.000 description 1
- 208000009889 Herpes Simplex Diseases 0.000 description 1
- 208000007514 Herpes zoster Diseases 0.000 description 1
- 102000003964 Histone deacetylase Human genes 0.000 description 1
- 108090000353 Histone deacetylase Proteins 0.000 description 1
- 101000819503 Homo sapiens 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase 9 Proteins 0.000 description 1
- 101001022183 Homo sapiens 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase FUT5 Proteins 0.000 description 1
- 101001022175 Homo sapiens 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase FUT6 Proteins 0.000 description 1
- 101100268553 Homo sapiens APP gene Proteins 0.000 description 1
- 101000862183 Homo sapiens Alpha-(1,3)-fucosyltransferase 10 Proteins 0.000 description 1
- 101000862213 Homo sapiens Alpha-(1,3)-fucosyltransferase 11 Proteins 0.000 description 1
- 101000819497 Homo sapiens Alpha-(1,3)-fucosyltransferase 7 Proteins 0.000 description 1
- 101000924727 Homo sapiens Alternative prion protein Proteins 0.000 description 1
- 101100494125 Homo sapiens BIRC5 gene Proteins 0.000 description 1
- 101000851684 Homo sapiens Chimeric ERCC6-PGBD3 protein Proteins 0.000 description 1
- 101000920783 Homo sapiens DNA excision repair protein ERCC-6 Proteins 0.000 description 1
- 101000618531 Homo sapiens DNA repair protein complementing XP-A cells Proteins 0.000 description 1
- 101000618535 Homo sapiens DNA repair protein complementing XP-C cells Proteins 0.000 description 1
- 101000848187 Homo sapiens Fanconi anemia group M protein Proteins 0.000 description 1
- 101001054334 Homo sapiens Interferon beta Proteins 0.000 description 1
- 101100510266 Homo sapiens KLF4 gene Proteins 0.000 description 1
- 101001091379 Homo sapiens Kallikrein-5 Proteins 0.000 description 1
- 101001038034 Homo sapiens Lysophosphatidic acid receptor 6 Proteins 0.000 description 1
- 101000573901 Homo sapiens Major prion protein Proteins 0.000 description 1
- 101000669513 Homo sapiens Metalloproteinase inhibitor 1 Proteins 0.000 description 1
- 101000741967 Homo sapiens Presequence protease, mitochondrial Proteins 0.000 description 1
- 101000883798 Homo sapiens Probable ATP-dependent RNA helicase DDX53 Proteins 0.000 description 1
- 101000585703 Homo sapiens Protein L-Myc Proteins 0.000 description 1
- 101000608194 Homo sapiens Pyrin domain-containing protein 1 Proteins 0.000 description 1
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
- 101000766306 Homo sapiens Serotransferrin Proteins 0.000 description 1
- 101000687905 Homo sapiens Transcription factor SOX-2 Proteins 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- 102100040203 Hyaluronan synthase 1 Human genes 0.000 description 1
- 101710197057 Hyaluronan synthase 1 Proteins 0.000 description 1
- 101710197056 Hyaluronan synthase 2 Proteins 0.000 description 1
- 102100040206 Hyaluronan synthase 2 Human genes 0.000 description 1
- 102100029425 Hyaluronan synthase 3 Human genes 0.000 description 1
- 101710197055 Hyaluronan synthase 3 Proteins 0.000 description 1
- 206010020649 Hyperkeratosis Diseases 0.000 description 1
- 208000008017 Hypohidrosis Diseases 0.000 description 1
- 208000003367 Hypopigmentation Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 206010021531 Impetigo Diseases 0.000 description 1
- 208000002078 Ingrown Nails Diseases 0.000 description 1
- 208000006877 Insect Bites and Stings Diseases 0.000 description 1
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
- 102100037852 Insulin-like growth factor I Human genes 0.000 description 1
- 102100026720 Interferon beta Human genes 0.000 description 1
- 101710089751 Interferon-induced, double-stranded RNA-activated protein kinase Proteins 0.000 description 1
- 102100034170 Interferon-induced, double-stranded RNA-activated protein kinase Human genes 0.000 description 1
- 102000003814 Interleukin-10 Human genes 0.000 description 1
- 108090000174 Interleukin-10 Proteins 0.000 description 1
- 108090000176 Interleukin-13 Proteins 0.000 description 1
- 102000003816 Interleukin-13 Human genes 0.000 description 1
- 101150070299 KLF4 gene Proteins 0.000 description 1
- 108060005987 Kallikrein Proteins 0.000 description 1
- 102000001399 Kallikrein Human genes 0.000 description 1
- 102100034868 Kallikrein-5 Human genes 0.000 description 1
- 206010023330 Keloid scar Diseases 0.000 description 1
- 108010076876 Keratins Proteins 0.000 description 1
- 102000011782 Keratins Human genes 0.000 description 1
- 206010066295 Keratosis pilaris Diseases 0.000 description 1
- 241000235058 Komagataella pastoris Species 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- 241000713666 Lentivirus Species 0.000 description 1
- 206010024434 Lichen sclerosus Diseases 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 229930184725 Lipoxin Natural products 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 101710149751 Lysophosphatidic acid receptor 6 Proteins 0.000 description 1
- 101150039798 MYC gene Proteins 0.000 description 1
- 102100025818 Major prion protein Human genes 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- 102000000380 Matrix Metalloproteinase 1 Human genes 0.000 description 1
- 108010016113 Matrix Metalloproteinase 1 Proteins 0.000 description 1
- 239000000637 Melanocyte-Stimulating Hormone Substances 0.000 description 1
- 108010007013 Melanocyte-Stimulating Hormones Proteins 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 102100039364 Metalloproteinase inhibitor 1 Human genes 0.000 description 1
- FQISKWAFAHGMGT-SGJOWKDISA-M Methylprednisolone sodium succinate Chemical compound [Na+].C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)COC(=O)CCC([O-])=O)CC[C@H]21 FQISKWAFAHGMGT-SGJOWKDISA-M 0.000 description 1
- 241001448624 Miliaria Species 0.000 description 1
- 108091027977 Mir-200 Proteins 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- 101100293199 Mus musculus Myc gene Proteins 0.000 description 1
- 101100137157 Mus musculus Pou5f1 gene Proteins 0.000 description 1
- 101000650589 Mus musculus Roundabout homolog 3 Proteins 0.000 description 1
- XCUAIINAJCDIPM-XVFCMESISA-N N(4)-hydroxycytidine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=NO)C=C1 XCUAIINAJCDIPM-XVFCMESISA-N 0.000 description 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- DZTHIGRZJZPRDV-LBPRGKRZSA-N N-acetyl-L-tryptophan Chemical compound C1=CC=C2C(C[C@H](NC(=O)C)C(O)=O)=CNC2=C1 DZTHIGRZJZPRDV-LBPRGKRZSA-N 0.000 description 1
- QIAFMBKCNZACKA-UHFFFAOYSA-N N-benzoylglycine Chemical compound OC(=O)CNC(=O)C1=CC=CC=C1 QIAFMBKCNZACKA-UHFFFAOYSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- FABQUVYDAXWUQP-UHFFFAOYSA-N N4-(1,3-benzodioxol-5-ylmethyl)-6-(3-methoxyphenyl)pyrimidine-2,4-diamine Chemical compound COC1=CC=CC(C=2N=C(N)N=C(NCC=3C=C4OCOC4=CC=3)C=2)=C1 FABQUVYDAXWUQP-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- DZTHIGRZJZPRDV-UHFFFAOYSA-N Nalpha-Acetyltryptophan Natural products C1=CC=C2C(CC(NC(=O)C)C(O)=O)=CNC2=C1 DZTHIGRZJZPRDV-UHFFFAOYSA-N 0.000 description 1
- 108700026371 Nanog Homeobox Proteins 0.000 description 1
- 102000055601 Nanog Homeobox Human genes 0.000 description 1
- 101100438378 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) fac-1 gene Proteins 0.000 description 1
- 101100326803 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) fac-2 gene Proteins 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- 208000007256 Nevus Diseases 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 208000007944 Nodular Nonsuppurative Panniculitis Diseases 0.000 description 1
- 206010072139 Ocular rosacea Diseases 0.000 description 1
- 208000007027 Oral Candidiasis Diseases 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 102100034925 P-selectin glycoprotein ligand 1 Human genes 0.000 description 1
- 108010054395 P-selectin ligand protein Proteins 0.000 description 1
- 102100035593 POU domain, class 2, transcription factor 1 Human genes 0.000 description 1
- 101710084414 POU domain, class 2, transcription factor 1 Proteins 0.000 description 1
- 101150082761 POU5F1 gene Proteins 0.000 description 1
- 206010033546 Pallor Diseases 0.000 description 1
- 206010033554 Palmoplantar keratoderma Diseases 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 201000011152 Pemphigus Diseases 0.000 description 1
- 241000286209 Phasianidae Species 0.000 description 1
- 208000000528 Pilonidal Sinus Diseases 0.000 description 1
- 206010035043 Pilonidal cyst Diseases 0.000 description 1
- 241000101040 Pityriasis Species 0.000 description 1
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 1
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 1
- 206010036186 Porphyria non-acute Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 102000004257 Potassium Channel Human genes 0.000 description 1
- 102100038632 Presequence protease, mitochondrial Human genes 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 102100038236 Probable ATP-dependent RNA helicase DDX53 Human genes 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 101800004937 Protein C Proteins 0.000 description 1
- 102000017975 Protein C Human genes 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 102100030128 Protein L-Myc Human genes 0.000 description 1
- 206010051292 Protein S Deficiency Diseases 0.000 description 1
- 108010067787 Proteoglycans Proteins 0.000 description 1
- 102000016611 Proteoglycans Human genes 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 208000001818 Pseudofolliculitis barbae Diseases 0.000 description 1
- 201000001263 Psoriatic Arthritis Diseases 0.000 description 1
- 208000036824 Psoriatic arthropathy Diseases 0.000 description 1
- 206010037575 Pustular psoriasis Diseases 0.000 description 1
- 102000002490 Rad51 Recombinase Human genes 0.000 description 1
- 108010068097 Rad51 Recombinase Proteins 0.000 description 1
- 208000032039 Rare urticaria Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 1
- 241001068263 Replication competent viruses Species 0.000 description 1
- 241001303601 Rosacea Species 0.000 description 1
- 208000000791 Rothmund-Thomson syndrome Diseases 0.000 description 1
- 101001053942 Saccharolobus solfataricus (strain ATCC 35092 / DSM 1617 / JCM 11322 / P2) Diphosphomevalonate decarboxylase Proteins 0.000 description 1
- 101800001700 Saposin-D Proteins 0.000 description 1
- 241000447727 Scabies Species 0.000 description 1
- 206010039792 Seborrhoea Diseases 0.000 description 1
- 206010040829 Skin discolouration Diseases 0.000 description 1
- 108010052164 Sodium Channels Proteins 0.000 description 1
- 102000018674 Sodium Channels Human genes 0.000 description 1
- 206010041303 Solar dermatitis Diseases 0.000 description 1
- 101150037203 Sox2 gene Proteins 0.000 description 1
- 208000003589 Spider Bites Diseases 0.000 description 1
- 208000000277 Splenic Neoplasms Diseases 0.000 description 1
- 208000031726 Spotted Fever Group Rickettsiosis Diseases 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 102000019197 Superoxide Dismutase Human genes 0.000 description 1
- 108010012715 Superoxide dismutase Proteins 0.000 description 1
- 230000024932 T cell mediated immunity Effects 0.000 description 1
- 102000003141 Tachykinin Human genes 0.000 description 1
- 229920002253 Tannate Polymers 0.000 description 1
- 108091046869 Telomeric non-coding RNA Proteins 0.000 description 1
- 108010055044 Tetanus Toxin Proteins 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 208000007712 Tinea Versicolor Diseases 0.000 description 1
- 206010056131 Tinea versicolour Diseases 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- 201000005485 Toxoplasmosis Diseases 0.000 description 1
- 108700009124 Transcription Initiation Site Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 108020004566 Transfer RNA Proteins 0.000 description 1
- 206010051446 Transient acantholytic dermatosis Diseases 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- 241000331598 Trombiculidae Species 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 241000287411 Turdidae Species 0.000 description 1
- 108010057266 Type A Botulinum Toxins Proteins 0.000 description 1
- 230000006750 UV protection Effects 0.000 description 1
- 229910052770 Uranium Inorganic materials 0.000 description 1
- 206010046740 Urticaria cholinergic Diseases 0.000 description 1
- 206010052568 Urticaria chronic Diseases 0.000 description 1
- 206010046751 Urticaria physical Diseases 0.000 description 1
- 206010046865 Vaccinia virus infection Diseases 0.000 description 1
- 206010046996 Varicose vein Diseases 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 229930003316 Vitamin D Natural products 0.000 description 1
- 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 1
- 208000000260 Warts Diseases 0.000 description 1
- 208000026736 Weber-Christian disease Diseases 0.000 description 1
- 208000018839 Wilson disease Diseases 0.000 description 1
- 206010048218 Xeroderma Diseases 0.000 description 1
- 108700031763 Xeroderma Pigmentosum Group D Proteins 0.000 description 1
- 206010048222 Xerosis Diseases 0.000 description 1
- SIIZPVYVXNXXQG-KGXOGWRBSA-N [(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-4-[[(3s,4r)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-3-hydroxyoxolan-2-yl]methyl [(2r,4r,5r)-2-(6-aminopurin-9-yl)-4-hydroxy-5-(phosphonooxymethyl)oxolan-3-yl] hydrogen phosphate Polymers C1=NC2=C(N)N=CN=C2N1[C@@H]1O[C@H](COP(O)(=O)OC2[C@@H](O[C@H](COP(O)(O)=O)[C@H]2O)N2C3=NC=NC(N)=C3N=C2)[C@@H](O)[C@H]1OP(O)(=O)OCC([C@@H](O)[C@H]1O)OC1N1C(N=CN=C2N)=C2N=C1 SIIZPVYVXNXXQG-KGXOGWRBSA-N 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- HBXQACAAUXRXBW-JXOAFFINSA-N [[(2R,3S,4R,5R)-5-(4-amino-5-formyl-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound P(O)(=O)(OP(=O)(O)OP(=O)(O)O)OC[C@@H]1[C@H]([C@H]([C@@H](O1)N1C(=O)N=C(N)C(=C1)C=O)O)O HBXQACAAUXRXBW-JXOAFFINSA-N 0.000 description 1
- ZUZUHROPOMGOKE-ZOQUXTDFSA-N [[(2r,3s,4r,5r)-3,4-dihydroxy-5-[4-(methylamino)-2-oxopyrimidin-1-yl]oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound O=C1N=C(NC)C=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 ZUZUHROPOMGOKE-ZOQUXTDFSA-N 0.000 description 1
- VEWJOCYCKIZKKV-GBNDHIKLSA-N [[(2r,3s,4r,5s)-5-(2,4-dioxo-1h-pyrimidin-5-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1C1=CNC(=O)NC1=O VEWJOCYCKIZKKV-GBNDHIKLSA-N 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000005299 abrasion Methods 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 208000009621 actinic keratosis Diseases 0.000 description 1
- 108010023082 activin A Proteins 0.000 description 1
- 229960001456 adenosine triphosphate Drugs 0.000 description 1
- 208000011589 adenoviridae infectious disease Diseases 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 210000001552 airway epithelial cell Anatomy 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 231100000360 alopecia Toxicity 0.000 description 1
- 208000004631 alopecia areata Diseases 0.000 description 1
- OBETXYAYXDNJHR-UHFFFAOYSA-N alpha-ethylcaproic acid Natural products CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-N 0.000 description 1
- 235000020661 alpha-linolenic acid Nutrition 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 239000003098 androgen Substances 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000001857 anti-mycotic effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 238000011319 anticancer therapy Methods 0.000 description 1
- 239000002543 antimycotic Substances 0.000 description 1
- 230000006851 antioxidant defense Effects 0.000 description 1
- 101150031224 app gene Proteins 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 101150010487 are gene Proteins 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 210000003050 axon Anatomy 0.000 description 1
- 230000036621 balding Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 208000005980 beta thalassemia Diseases 0.000 description 1
- 229960002537 betamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-DVTGEIKXSA-N betamethasone 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-DVTGEIKXSA-N 0.000 description 1
- 239000003833 bile salt Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 210000002449 bone cell Anatomy 0.000 description 1
- 229940094657 botulinum toxin type a Drugs 0.000 description 1
- 238000002725 brachytherapy Methods 0.000 description 1
- 229940077737 brain-derived neurotrophic factor Drugs 0.000 description 1
- 210000001217 buttock Anatomy 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 229910001576 calcium mineral Inorganic materials 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 201000003984 candidiasis Diseases 0.000 description 1
- 101150071218 cap3 gene Proteins 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 231100000259 cardiotoxicity Toxicity 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000027902 cell growth involved in cardiac muscle cell development Effects 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000010307 cell transformation Effects 0.000 description 1
- 230000003822 cell turnover Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- JOYKCMAPFCSKNO-UHFFFAOYSA-N chloro benzenesulfonate Chemical compound ClOS(=O)(=O)C1=CC=CC=C1 JOYKCMAPFCSKNO-UHFFFAOYSA-N 0.000 description 1
- KVSASDOGYIBWTA-UHFFFAOYSA-N chloro benzoate Chemical compound ClOC(=O)C1=CC=CC=C1 KVSASDOGYIBWTA-UHFFFAOYSA-N 0.000 description 1
- QPAKKWCQMHUHNI-GQIQPHNSSA-N chlorotoxin Chemical compound C([C@H]1C(=O)NCC(=O)N2CCC[C@H]2C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H]4CSSC[C@@H](C(N[C@@H](CCSC)C(=O)N5CCC[C@H]5C(=O)N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CCCNC(N)=N)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)CNC(=O)CNC(=O)[C@H](CSSC[C@H](NC(=O)[C@H](CC(C)C)NC2=O)C(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC4=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N3)=O)NC(=O)[C@@H](N)CCSC)C1=CC=C(O)C=C1 QPAKKWCQMHUHNI-GQIQPHNSSA-N 0.000 description 1
- 229960005534 chlorotoxin Drugs 0.000 description 1
- 230000001713 cholinergic effect Effects 0.000 description 1
- 201000005681 cholinergic urticaria Diseases 0.000 description 1
- 210000003483 chromatin Anatomy 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000024376 chronic urticaria Diseases 0.000 description 1
- 229940114081 cinnamate Drugs 0.000 description 1
- 230000027288 circadian rhythm Effects 0.000 description 1
- 229940001468 citrate Drugs 0.000 description 1
- 206010009869 cold urticaria Diseases 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 230000009918 complex formation Effects 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000000315 cryotherapy Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 201000010251 cutis laxa Diseases 0.000 description 1
- 208000031513 cyst Diseases 0.000 description 1
- PCDQPRRSZKQHHS-ZAKLUEHWSA-N cytidine-5'-triphosphate Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO[P@](O)(=O)O[P@@](O)(=O)OP(O)(O)=O)O1 PCDQPRRSZKQHHS-ZAKLUEHWSA-N 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 229960005029 darbepoetin alfa Drugs 0.000 description 1
- GHVNFZFCNZKVNT-UHFFFAOYSA-M decanoate Chemical compound CCCCCCCCCC([O-])=O GHVNFZFCNZKVNT-UHFFFAOYSA-M 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000002242 deionisation method Methods 0.000 description 1
- 238000001739 density measurement Methods 0.000 description 1
- 210000005258 dental pulp stem cell Anatomy 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 238000002845 discoloration Methods 0.000 description 1
- MWEQTWJABOLLOS-UHFFFAOYSA-L disodium;[[[5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-oxidophosphoryl] hydrogen phosphate;trihydrate Chemical group O.O.O.[Na+].[Na+].C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP([O-])(=O)OP(O)([O-])=O)C(O)C1O MWEQTWJABOLLOS-UHFFFAOYSA-L 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 231100000594 drug induced liver disease Toxicity 0.000 description 1
- 208000013046 dyshidrosis Diseases 0.000 description 1
- 210000005069 ears Anatomy 0.000 description 1
- 210000003981 ectoderm Anatomy 0.000 description 1
- 230000005518 electrochemistry Effects 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 210000001671 embryonic stem cell Anatomy 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 210000001900 endoderm Anatomy 0.000 description 1
- 230000002616 endonucleolytic effect Effects 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 201000008220 erythropoietic protoporphyria Diseases 0.000 description 1
- 229940105423 erythropoietin Drugs 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- GXHVDDBBWDCOTF-UHFFFAOYSA-N ever-1 Natural products CCC(C)C(=O)OC1C(CC(C)C23OC(C)(C)C(CC(OC(=O)c4cccnc4)C12COC(=O)C)C3OC(=O)C)OC(=O)C GXHVDDBBWDCOTF-UHFFFAOYSA-N 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 210000004709 eyebrow Anatomy 0.000 description 1
- 210000000720 eyelash Anatomy 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 229940098448 fibroblast growth factor 7 Drugs 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 108091006047 fluorescent proteins Proteins 0.000 description 1
- 102000034287 fluorescent proteins Human genes 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 210000001061 forehead Anatomy 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 201000010175 gallbladder cancer Diseases 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 102000054767 gene variant Human genes 0.000 description 1
- 210000004392 genitalia Anatomy 0.000 description 1
- 210000001654 germ layer Anatomy 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 108010024847 glutamate decarboxylase 1 Proteins 0.000 description 1
- 108010024780 glutamate decarboxylase 2 Proteins 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
- 206010018797 guttate psoriasis Diseases 0.000 description 1
- 230000003803 hair density Effects 0.000 description 1
- 210000003780 hair follicle Anatomy 0.000 description 1
- 230000003779 hair growth Effects 0.000 description 1
- 208000024963 hair loss Diseases 0.000 description 1
- 230000003676 hair loss Effects 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 231100000304 hepatotoxicity Toxicity 0.000 description 1
- 230000007686 hepatotoxicity Effects 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
- 208000003215 hereditary nephritis Diseases 0.000 description 1
- 238000013537 high throughput screening Methods 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 102000053563 human MYC Human genes 0.000 description 1
- 102000052983 human POU5F1 Human genes 0.000 description 1
- 102000047444 human SOX2 Human genes 0.000 description 1
- 239000000416 hydrocolloid Substances 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 239000008350 hydrogenated phosphatidyl choline Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 208000000069 hyperpigmentation Diseases 0.000 description 1
- 230000003810 hyperpigmentation Effects 0.000 description 1
- 230000003425 hypopigmentation Effects 0.000 description 1
- 238000002952 image-based readout Methods 0.000 description 1
- DOUYETYNHWVLEO-UHFFFAOYSA-N imiquimod Chemical compound C1=CC=CC2=C3N(CC(C)C)C=NC3=C(N)N=C21 DOUYETYNHWVLEO-UHFFFAOYSA-N 0.000 description 1
- 229960002751 imiquimod Drugs 0.000 description 1
- 230000007124 immune defense Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 210000001613 integumentary system Anatomy 0.000 description 1
- 229940076144 interleukin-10 Drugs 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 239000002085 irritant Substances 0.000 description 1
- 231100000021 irritant Toxicity 0.000 description 1
- 208000001875 irritant dermatitis Diseases 0.000 description 1
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
- TWBYWOBDOCUKOW-UHFFFAOYSA-M isonicotinate Chemical compound [O-]C(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-M 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 206010024217 lentigo Diseases 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 150000002617 leukotrienes Chemical class 0.000 description 1
- 201000011486 lichen planus Diseases 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 229960004488 linolenic acid Drugs 0.000 description 1
- 150000002639 lipoxins Chemical class 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 108010082117 matrigel Proteins 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000005541 medical transmission Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 210000003716 mesoderm Anatomy 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229910052752 metalloid Inorganic materials 0.000 description 1
- 150000002738 metalloids Chemical class 0.000 description 1
- 239000003475 metalloproteinase inhibitor Substances 0.000 description 1
- IZYBEMGNIUSSAX-UHFFFAOYSA-N methyl benzenecarboperoxoate Chemical compound COOC(=O)C1=CC=CC=C1 IZYBEMGNIUSSAX-UHFFFAOYSA-N 0.000 description 1
- 229940095102 methyl benzoate Drugs 0.000 description 1
- 229960004584 methylprednisolone Drugs 0.000 description 1
- 108091030789 miR-302 stem-loop Proteins 0.000 description 1
- 108091062637 miR-367 stem-loop Proteins 0.000 description 1
- 108091057188 miR-369 stem-loop Proteins 0.000 description 1
- 210000001724 microfibril Anatomy 0.000 description 1
- 108700005457 microfibrillar Proteins 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 208000008588 molluscum contagiosum Diseases 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 1
- 229940116191 n-acetyltryptophan Drugs 0.000 description 1
- 210000000282 nail Anatomy 0.000 description 1
- 230000036562 nail growth Effects 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical class C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical class C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 102000034288 naturally occurring fusion proteins Human genes 0.000 description 1
- 108091006048 naturally occurring fusion proteins Proteins 0.000 description 1
- 210000003739 neck Anatomy 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 210000001178 neural stem cell Anatomy 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 239000002581 neurotoxin Substances 0.000 description 1
- 231100000618 neurotoxin Toxicity 0.000 description 1
- 201000005734 nevoid basal cell carcinoma syndrome Diseases 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 210000000287 oocyte Anatomy 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 210000004409 osteocyte Anatomy 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 230000037324 pain perception Effects 0.000 description 1
- 201000008743 palmoplantar keratosis Diseases 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 206010033675 panniculitis Diseases 0.000 description 1
- 229940014662 pantothenate Drugs 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 239000011713 pantothenic acid Substances 0.000 description 1
- 208000003154 papilloma Diseases 0.000 description 1
- 208000029211 papillomatosis Diseases 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 102000007863 pattern recognition receptors Human genes 0.000 description 1
- 108010089193 pattern recognition receptors Proteins 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 201000001976 pemphigus vulgaris Diseases 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 238000009527 percussion Methods 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- DYUMLJSJISTVPV-UHFFFAOYSA-N phenyl propanoate Chemical compound CCC(=O)OC1=CC=CC=C1 DYUMLJSJISTVPV-UHFFFAOYSA-N 0.000 description 1
- 229940049953 phenylacetate Drugs 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 229950009215 phenylbutanoic acid Drugs 0.000 description 1
- 150000008105 phosphatidylcholines Chemical class 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 201000002881 physical urticaria Diseases 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 206010035114 pityriasis rosea Diseases 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 201000011414 pompholyx Diseases 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 108020001213 potassium channel Proteins 0.000 description 1
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 235000013594 poultry meat Nutrition 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 229960005205 prednisolone Drugs 0.000 description 1
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[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 OIGNJSKKLXVSLS-VWUMJDOOSA-N 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
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- UORVCLMRJXCDCP-UHFFFAOYSA-M propynoate Chemical compound [O-]C(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-M 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 229960000856 protein c Drugs 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 230000018883 protein targeting Effects 0.000 description 1
- XNSAINXGIQZQOO-SRVKXCTJSA-N protirelin Chemical compound NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H]1NC(=O)CC1)CC1=CN=CN1 XNSAINXGIQZQOO-SRVKXCTJSA-N 0.000 description 1
- 208000014235 psoriasis 9 Diseases 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000003938 response to stress Effects 0.000 description 1
- 238000002435 rhinoplasty Methods 0.000 description 1
- 108020004418 ribosomal RNA Proteins 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 108010074523 rimabotulinumtoxinB Proteins 0.000 description 1
- 239000011435 rock Substances 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 208000005687 scabies Diseases 0.000 description 1
- 210000004761 scalp Anatomy 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 230000037390 scarring Effects 0.000 description 1
- 230000037387 scars Effects 0.000 description 1
- 229940116351 sebacate Drugs 0.000 description 1
- CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 208000002491 severe combined immunodeficiency Diseases 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 150000004666 short chain fatty acids Chemical class 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 230000037393 skin firmness Effects 0.000 description 1
- 230000037067 skin hydration Effects 0.000 description 1
- 201000010153 skin papilloma Diseases 0.000 description 1
- 201000000195 skin tag Diseases 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 201000002471 spleen cancer Diseases 0.000 description 1
- 201000004284 spotted fever Diseases 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 210000002536 stromal cell Anatomy 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 210000004304 subcutaneous tissue Anatomy 0.000 description 1
- TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
- 229940086735 succinate Drugs 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 230000000475 sunscreen effect Effects 0.000 description 1
- 239000000516 sunscreening agent Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 208000010648 susceptibility to HIV infection Diseases 0.000 description 1
- 208000032273 susceptibility to psoriasis 9 Diseases 0.000 description 1
- 230000035900 sweating Effects 0.000 description 1
- 210000002504 synaptic vesicle Anatomy 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 108060008037 tachykinin Proteins 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 108091035539 telomere Proteins 0.000 description 1
- 102000055501 telomere Human genes 0.000 description 1
- 210000003411 telomere Anatomy 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940118376 tetanus toxin Drugs 0.000 description 1
- CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
- CFMYXEVWODSLAX-QOZOJKKESA-N tetrodotoxin Chemical compound O([C@@]([C@H]1O)(O)O[C@H]2[C@@]3(O)CO)[C@H]3[C@@H](O)[C@]11[C@H]2[C@@H](O)N=C(N)N1 CFMYXEVWODSLAX-QOZOJKKESA-N 0.000 description 1
- 229950010357 tetrodotoxin Drugs 0.000 description 1
- CFMYXEVWODSLAX-UHFFFAOYSA-N tetrodotoxin Natural products C12C(O)NC(=N)NC2(C2O)C(O)C3C(CO)(O)C1OC2(O)O3 CFMYXEVWODSLAX-UHFFFAOYSA-N 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 230000003813 thin hair Effects 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 150000003595 thromboxanes Chemical class 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 201000004647 tinea pedis Diseases 0.000 description 1
- 210000003371 toe Anatomy 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 231100000041 toxicology testing Toxicity 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M trans-cinnamate Chemical compound [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- 230000002463 transducing effect Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- RUDATBOHQWOJDD-UZVSRGJWSA-N ursodeoxycholic acid Chemical compound C([C@H]1C[C@@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-UZVSRGJWSA-N 0.000 description 1
- 230000002568 urticarial effect Effects 0.000 description 1
- 208000007089 vaccinia Diseases 0.000 description 1
- 208000027185 varicose disease Diseases 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- GDJZZWYLFXAGFH-UHFFFAOYSA-M xylenesulfonate group Chemical group C1(C(C=CC=C1)C)(C)S(=O)(=O)[O-] GDJZZWYLFXAGFH-UHFFFAOYSA-M 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/39—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
- A61B18/18—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
- A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
- A61K31/7072—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/7105—Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/711—Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/713—Double-stranded nucleic acids or oligonucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/38—Albumins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/44—Oxidoreductases (1)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/45—Transferases (2)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/46—Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/60—Sugars; Derivatives thereof
- A61K8/606—Nucleosides; Nucleotides; Nucleic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0021—Intradermal administration, e.g. through microneedle arrays, needleless injectors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/08—Antiseborrheics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/10—Anti-acne agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/12—Keratolytics, e.g. wart or anti-corn preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/16—Emollients or protectives, e.g. against radiation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/10—Antioedematous agents; Diuretics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/008—Preparations for oily skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/06—Preparations for care of the skin for countering cellulitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/78—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
- C12N15/102—Mutagenizing nucleic acids
- C12N15/1024—In vivo mutagenesis using high mutation rate "mutator" host strains by inserting genetic material, e.g. encoding an error prone polymerase, disrupting a gene for mismatch repair
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/10—Transferases (2.)
- C12N9/12—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
- A61B2018/00315—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body for treatment of particular body parts
- A61B2018/00452—Skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
- A61B18/18—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves
- A61B2018/1807—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using light other than laser radiation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
- A61K2800/83—Electrophoresis; Electrodes; Electrolytic phenomena
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
- A61K2800/91—Injection
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/80—Fusion polypeptide containing a DNA binding domain, e.g. Lacl or Tet-repressor
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Dermatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Zoology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- Wood Science & Technology (AREA)
- Immunology (AREA)
- General Engineering & Computer Science (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Microbiology (AREA)
- Plant Pathology (AREA)
- Hematology (AREA)
- Virology (AREA)
- Diabetes (AREA)
- Heart & Thoracic Surgery (AREA)
- Surgery (AREA)
- Dispersion Chemistry (AREA)
- Birds (AREA)
- Gerontology & Geriatric Medicine (AREA)
Description
本出願は、全内容が全体として参照により本明細書に組み込まれる、2014年1月31日に出願された米国仮特許出願第61/934,397号、2014年8月18日に出願された米国仮特許出願第62/038,608号、及び2014年10月28日に出願された米国仮特許出願第62/069,667号に対する優先権を主張する。
本発明は部分的に、細胞、組織、器官、及び患者に、核酸を生成及び送達するための方法、組成物、及び製品;細胞、組織、器官、及び患者においてタンパク質を発現させるための方法;ならびにこれらの方法、組成物、及び製品を用いて生成される細胞、治療薬、及び化粧品に関する。
本明細書と共に電子的に提出されたテキストファイルの内容は、全体として参照により本明細書に組み込まれる。配列表のコンピュータ可読フォーマットコピー(ファイル名:FAB-008PC SequenceListing.txt、記録日:2015年1月30日、ファイルサイズ:929KB)。
リボ核酸(RNA)は、原核細胞及び真核細胞の両方に遍在し、そこで、メッセンジャーRNAの形態で遺伝情報をコードし、トランスファーRNAの形態でアミノ酸を結合及び輸送し、リボソームRNAの形態でアミノ酸をタンパク質に組み立て、マイクロRNA及び長い非コードRNAの形態で遺伝子発現制御を含む多数の他の機能を行う。RNAは、直接的な化学合成及びインビトロ転写を含む方法により、合成的に生成することができ、治療的使用のために患者に投与することができる。しかし、以前に記載されている合成RNA分子は、ヒト細胞において不安定であり、強力な先天性免疫応答を誘発する。加えて、患者、器官、組織、及びインビボの細胞に、核酸を効率的に非ウイルス的送達するための方法は、以前に記載されていない。既存の合成RNA技術及び核酸の送達のための方法の多くの欠点により、それらの技術及び方法が、治療的または美容的使用にとって望ましくないものになる。
細胞は、それらを、特定の細胞外キュー(cues)に曝露させることにより、及び/または特定のタンパク質、マイクロRNAなどの異所性発現によりリプログラミングすることができる。いくつかのリプログラミング方法が以前に記載されているが、異所性発現に依存するほとんどのものは、変異の危険を伴う可能性がある外来DNAの導入を必要とする。リプログラミングタンパク質の直接送達に基づく、DNAフリーのリプログラミング方法が報告されている。しかし、これらの方法は商業的使用には、あまりにも非効率的で信頼できない。加えて、RNAベースのリプログラミング方法が記載されている(例えば、Angel. MIT Thesis.2008.1-56;Angel et al.PLoS ONE.2010.5,107、Warren et al.Cell Stem Cell.2010.7,618-630;Angel.MIT Thesis.2011.1-89、及びLee et al.Cell.2012.151,547-558(これらの全ての内容は、参照により本明細書に組み込まれる)を参照のこと)。しかし、既存のRNAベースのリプログラミング方法は、成熟細胞に実施される場合、時間がかかり、信頼できず、非効率的であり、(著しい費用及びエラーの可能性をもたらす)多くのトランスフェクションを必要とし、限られた数の細胞型のみをリプログラミングすることができ、限られた数の細胞型しかリプログラミングすることができず、免疫抑制剤の使用を必要とし、血液由来HSA及びヒト線維芽細胞フィーダーを含む複数のヒト由来構成成分の使用を必要とする。以前に開示されたRNAベースのリプログラミング方法の多くの欠点により、それらの方法が、インビボでの使用にとって望ましくないものになっている。
いくつかの自然発生タンパク質は、特定のDNA配列を認識することができるDNA結合ドメイン、例えば、ジンクフィンガー(ZF)及び転写活性化因子様エフェクター(TALE)を含有する。これらのDNA結合ドメイン及びFokIエンドヌクレアーゼの切断ドメインのうちの1つ以上を含有する融合タンパク質を、細胞内のDNAの所望の領域に、二本鎖切断を形成するために用いることができる(例えば、米国特許出願公開第US2012/0064620号、米国特許出願公開第US2011/0239315号、米国特許第8,470,973号、米国特許出願公開第US2013/0217119号、米国特許第8,420,782号、米国特許出願公開第US2011/0301073号、米国特許出願公開第US2011/0145940号、米国特許第8,450,471号、米国特許第8,440,431号、米国特許第8,440,432号、及び米国特許出願公開第2013/0122581号(これら全ての内容は、参照により本明細書に組み込まれる)を参照のこと)。しかし、細胞を遺伝子編集するための現在の方法は、非効率的であり、制御されない突然変異誘発の危険を伴い、それらの方法が、研究及び治療的使用の両方にとって望ましくないものとなっている。体細胞のDNAフリーの遺伝子編集のための方法は、以前に検討されておらず、体細胞の同時または順次の遺伝子編集及びリプログラミングのための方法もまた、検討されていない。加えて、患者において(即ち、インビボで)、細胞を直接遺伝子編集するための方法は、以前に検討されておらず、そのような方法の開発は、DNA結合ドメインの乏しい結合にある程度起因する、許容可能な標的の欠如、非効率的な送達、遺伝子編集タンパク質/タンパク質(複数)の非効率的な発現、発現された遺伝子編集タンパク質/タンパク質(複数)による非効率的な遺伝子編集;FokI切断ドメインの無向二量体形成及びDNA結合ドメインの乏しい特異性にある程度起因する、過剰なオフターゲット効果;ならびに他の要因により制限されている。最終的に、抗菌、抗ウイルス、及び抗癌治療における遺伝子編集の使用は、以前に検討されていない。
「分子」は、分子実体(分子、イオン、複合体など)を意味する。
緑色蛍光タンパク質またはヒトタンパク質エラスチン、チロシナーゼ、メラノコルチン1受容体、ヒアルロン酸合成酵素1、ヒアルロン酸合成酵素2、ヒアルロン酸合成酵素3、III型コラーゲンa1、VII型コラーゲンa1、インターロイキン10、P-セレクチン糖タンパク質リガンド1、α-(1,3)-フコシルトランスフェラーゼ(fucosyltransferase)のOct4、Sox2、Klf4、c-Myc-2(T58A)、及びLin28、またはヒト遺伝子XPA、CCR5、TERT、MYC、及びBIRC5を標的とするTALENをコードし、標準及び非標準ヌクレオチドの種々の組み合わせを含むRNAを、製造者の指示ならびに本発明者により先に開示された発明(米国特許出願第13/465,490号(現在米国特許第8,497,124号)、国際出願第PCT/US12/67966号、米国特許出願第13/931,251号、及び国際特許出願第PCT/US13/68118号、これら全ての内容は全体として参照により本明細書に組み込まれる)にしたがって、T7高収率RNA合成キット及びmRNAキャップ2′-O-メチルトランスフェラーゼを有するワクシニアキャッピングシステムキット(全てNew England Biolabs,Inc.製)を用いて、DNAテンプレートから合成した(表4)。次に、RNAを、100ng/μL~1000ng/μLまでヌクレアーゼ非含有水で希釈した。ある特定の実験のために、RNAse阻害剤(Superase・In、Life Technologies Corporation)を、RNA100μg当たり1μLの濃度で添加した。RNA溶液を4Cで保存した。リプログラミング実験のために、Oct4、Sox2、Klf4、c-Myc-2(T58A)、及びLin28をコードするRNAを、3:1:1:1:1のモル比で混合した。
6ウェルプレートでトランスフェクションするため、2μgのRNA及び6μLのトランスフェクション試薬(Lipofectamine RNAiMAX、Life Technologies Corporation)を、まず、複合体形成培地(Opti-MEM、Life Technologies Corporation、またはDMEM/F12+10μg/mLのインスリン+5.5μg/mLのトランスフェリン+6.7ng/mLの亜セレン酸ナトリウム+2μg/mLのエタノールアミン)で別々に希釈して、それぞれ60μLの総量にした。次に、希釈されたRNA及びトランスフェクション試薬を、トランスフェクション試薬の製造者の指示にしたがって、混合し、室温で15分間インキュベートした。次に、複合体を、培養中の細胞に添加した。12μL~240μLの複合体を、1ウェル当たり2mLのトランスフェクション培地を既に含有していた6ウェルプレートの各ウェルに添加した。プレートを穏やかに振盪して、複合体をウェル全体に分配させた。細胞を4時間から一晩、複合体とインキュベートした後、培地を新しいトランスフェクション培地(2mL/ウェル)と交換した。量を、24ウェル及び96ウェルプレートでのトランスフェクションのために減らした。あるいは、0.5μg~5μgのRNA、及びRNA1μg当たり2~3μLのトランスフェクション試薬(Lipofectamine 2000、Life Technologies Corporation)を、まず、複合体形成培地(Opti-MEM、Life Technologies Corporation、またはDMEM/F12+10μg/mLのインスリン+5.5μg/mLのトランスフェリン+6.7ng/mLの亜セレン酸ナトリウム+2μg/mLのエタノールアミン)で別々に希釈して、それぞれ5μL~100μLの総量にした。次に、希釈したRNA及びトランスフェクション試薬を、混合し、室温で10分間インキュベートした。次に、複合体を、培養中の細胞に添加した。10μL~200μLの複合体を、1ウェル当たり2mLのトランスフェクション培地を既に含有していた6ウェルプレートの各ウェルに添加した。ある特定の実験では、DMEM+10%のFBSまたはDMEM+50%のFBSを、トランスフェクション培地の代わりに使用した。プレートを穏やかに振盪して、複合体をウェル全体に分配させた。細胞を4時間から一晩、複合体とインキュベートした。ある特定の実験では、培地を、トランスフェクションの4時間後または24時間後に、新しいトランスフェクション培地(2mL/ウェル)と交換した。
初代ヒト線維芽細胞を、実施例1したがって合成されたRNAで、実施例2にしたがってトランスフェクションした。トランスフェクションの20~24時間後に、細胞を、Oct4に対する抗体を用いて固定及び染色した。RNAの相対的な毒性を、固定時の細胞密度を評価することにより決定した。
細胞培養培地を、核酸での細胞の効率的なトランスフェクション及び効率的なリプログラミングをサポートするように作成した(「トランスフェクション培地」):
DMEM/F12+15mMのHEPES+2mMのL-アラニル-L-グルタミン+10μg/mLのインスリン+5.5μg/mLのトランスフェリン+6.7ng/mLの亜セレン酸ナトリウム+2μg/mLのエタノールアミン+50μg/mLのL-アスコルビン酸2-フォスフェートセスキマグネシウム塩水和物+4μg/mLのコレステロール+1μMのヒドロコルチゾン+25μg/mLのポリオキシエチレンソルビタンモノオレート+2μg/mLのD-α-トコフェロールアセテート+20ng/mLのbFGF+5mg/mLの処理済みヒト血清アルブミン。
DMEM/F12+2mMのL-アラニル-L-グルタミン+10μg/mLのインスリン+5.5μg/mLのトランスフェリン+6.7ng/mLの亜セレン酸ナトリウム+2μg/mLのエタノールアミン+50μg/mLのL-アスコルビン酸2-フォスフェートセスキマグネシウム塩水和物+20ng/mLのbFGF+2ng/mLのTGF-β1。
培地を、細胞の効率的なトランスフェクション、リプログラミング、及び遺伝子編集をサポートするように作成した:
DMEM/F12+10μg/mLのインスリン+5.5μg/mLのトランスフェリン+6.7ng/mLの亜セレン酸ナトリウム+20ng/mLのbFGF+5mg/mLの処理済みヒト血清アルブミン。
DMEM/F12+15mMのHEPES+2mMのL-アラニル-L-グルタミン+10μg/mLのインスリン+5.5μg/mLのトランスフェリン+6.7ng/mLの亜セレン酸ナトリウム+2μg/mLのエタノールアミン+4.5μg/mLのコレステロール+10μg/mLのタラ肝油脂肪酸(メチルエステル)+25μg/mLポリオキシエチレンソルビタンモノオレート+2μg/mLのD-α-トコフェロールアセテート+1μg/mLのL-アスコルビン酸2-フォスフェートセスキマグネシウム塩水和物+0.1%のPluronic F-68+20ng/mLのbFGF+5mg/mLの処理済みヒト血清アルブミン。
DMEM/F12+15mMのHEPES+2mMのL-アラニル-L-グルタミン+10μg/mLのインスリン+5.5μg/mLのトランスフェリン+6.7ng/mLの亜セレン酸ナトリウム+2μg/mLのエタノールアミン+4.5μg/mLのコレステロール+1μMのヒドロコルチゾン+0~25μg/mLのポリオキシエチレンソルビタンモノオレート+2μg/mLのD-α-トコフェロールアセテート+50μg/mLのL-アスコルビン酸2-フォスフェートセスキマグネシウム塩水和物+20ng/mLのbFGF+5mg/mLの処理済みヒト血清アルブミン。
6ウェルプレートでトランスフェクションするため、2μgのRNA及び6μLのトランスフェクション試薬(Lipofectamine(商標) RNAiMAX、Life Technologies Corporation)を、まず、複合体形成培地(Opti-MEM(登録商標)、Life Technologies Corporation)で別々に希釈して、それぞれ60μLの総量にした。次に、希釈されたRNA及びトランスフェクション試薬を、トランスフェクション試薬の製造者の指示にしたがって、混合し、室温で15分間インキュベートした。次に、複合体を、培養中の細胞に添加した。30μL~240μLの複合体を、1ウェル当たり2mLのトランスフェクション培地を既に含有していた6ウェルプレートの各ウェルに添加した。次に、プレートを穏やかに振盪して、複合体をウェル全体に分配させた。細胞を2時間から一晩、複合体とインキュベートした後、培地を新しいトランスフェクション培地(2mL/ウェル)と交換した。量を、24ウェル及び96ウェルプレートでのトランスフェクションのために減らした。細胞を、Oct4に対する抗体を用いて、トランスフェクションの20~24時間後に固定及び染色した。核を染色及び計数し、RNAの相対的な毒性を決定した。
初代ヒト新生児線維芽細胞を、5mg/mLのHSAを含有または非含有の培地で培養した。コーンフラクションV(A6784、Sigma-Aldrich Co.LLC.)及び4つの異なる組換えHSA製剤(Sigma-Aldrich Co.LLC.製のA6608、A7736、A9731、及びA9986)をスクリーニングした。細胞を、実施例1したがって合成されたRNAで、実施例2にしたがってトランスフェクションした。トランスフェクションされていない細胞は、トランスフェクションされたウェル中の任意のHSA製剤を含有する培地でよく成長したが、HSA製剤のそれぞれにより、劇的に異なる細胞形態及び細胞密度が得られ、リプログラミングを示す形態上の変化はもたらされなかった。
10%のHSA溶液を、22mMの塩化ナトリウム及び16mMのオクタン酸ナトリウム(Sigma-Aldrich Co.LLC)とプレインキュベートし、完全培地の構築前の3時間に37Cでインキュベートした。
室温で穏やかに撹拌しながら、10mlのヌクレアーゼ非含有水に2gのHSAを溶解することにより、ピキア・パストリス(A7736、Sigma-Aldrich Co.LLC.)で産生された組換えHSAの20%溶液を調製した。次に、まず1gの混合床脱イオン化樹脂(AG 501-X8(D)、Bio-Rad Laboratories,Inc.)を添加し、室温で1時間揺動させることにより、HSA溶液を脱イオン化した。次に、HSA溶液を、5gの新しい樹脂を含有する管にデカントし、室温で4時間揺動させた。最後に、脱イオンHSA溶液を、デカントし、ヌクレアーゼ非含有水で10%の総タンパク質含有量に調整し、0.2μmのPESメンブレンフィルターを用いてフィルター滅菌し、4Cで保存した。
初代ヒト新生児線維芽細胞を、実施例8及び/または実施例9にしたがって処理された組換えHSAを含有する、または処理済み血漿由来HSA(Bio-Pure HSA、Biological Industries)を含有する培地中で培養した。0日目から、細胞を、実施例1にしたがって合成したRNAで、実施例2にしたがって毎日トランスフェクションした。画像を3日目に撮影した。間葉の上皮への移行に類似した形態変化を受けている細胞のいくつかの小さいエリアが、オクタノエートを含有するウェルで観察され、増大したトランスフェクション効率が示された。間葉の上皮への移行に類似した形態学的変化の多数の広いエリアが、処理済み血漿由来HSAを含有する試料で観察された。両方の場合において、形態学的変化は、リプログラミングの特徴であった。
初代ヒト新生児線維芽細胞を、5000細胞/ウェルの密度で、線維芽細胞培地(DMEM+10%ウシ胎児血清)の6ウェルプレートにプレーティングした。6時間後、培地を、オクタノエートで処理されたHSAを含有するトランスフェクション培地と交換した。0日目から、細胞を、実施例1にしたがって合成したRNAで、実施例2にしたがって毎日トランスフェクションした。5日目までに、ウェルには、リプログラミングに合致する形態を示す細胞のいくつかのエリアが含有された。この実験には、フィーダーまたは免疫抑制剤の使用が含まれなかった。
0日目から、初代ヒト新生児線維芽細胞を、実施例1したがって合成されたRNAで、実施例2にしたがってトランスフェクションした。画像を2日目に撮影した。未処理HSAを含有するウェル内の細胞は、処理済み血漿由来HSAを含有するウェルまたはイオン交換樹脂で処理された組換えHSAを含有するウェルのいずれと比較しても低い生存率を示した。
初代ヒト新生児線維芽細胞を、10,000細胞/ウェルの密度で、線維芽細胞培地(DMEM+10%ウシ胎児血清)のフィーダー上で6ウェルプレートにプレーティングした。0日目から、細胞を、実施例1にしたがって合成したRNAで、実施例2にしたがって毎日トランスフェクションした。1:20の分割比を伴う継代を、4日目に実施した。画像を10日目に撮影した。ウェルには、リプログラミングに合致する形態を示す細胞の多くの大きいコロニーが含有された。コロニーは、未処理HSAを含有する細胞培養培地に曝露したウェル内で観察されなかった。
初代ヒト線維芽細胞を、20,000細胞/ウェルの密度で、線維芽細胞培地(DMEM+10%ウシ胎児血清)の6ウェルプレートにプレーティングした。6時間後、培地を、処理済みHSAを含有する、または免疫抑制剤を含有しないトランスフェクション培地と交換し、細胞を、RNAの用量を1μg/ウェルまで減少させたこと、及び合計で5回トランスフェクションを実施したこと除いて、実施例1にしたがって合成したRNAで、実施例2にしたがって毎日トランスフェクションした。画像を7日目に撮影した。リプログラミングに合致する形態を示す細胞の小さなコロニーが、早くも5日目には見えるようになった。7日目に、培地を、DMEM/F12+20%Knockout(商標)Serum Replacement(Life Technologies Corporation)+1X非必須アミノ酸+2mMのL-グルタミンと交換し、24時間、照射したマウス胚性線維芽細胞で馴化し、次に20ng/mLのbFGF及び10μMのY-27632を補充した。リプログラミングされた形態を有する大きなコロニーが、早くも8日目には見えるようになった。コロニーを10日目に採取し、基底膜抽出物(Cultrex(登録商標)Human BME Pathclear(登録商標)、Trevigen Inc.)でコーティングされたウェルにプレーティングした。細胞は急速に成長し、継代されて株を樹立した。樹立された株は、多能性幹細胞マーカーOct4及びSSEA4に対して陽性染色された。全プロトコルを繰り返し、同様の結果が得られた。
全層皮膚のパンチ生検を、承認されたプロトコルにしたがって、健康な31歳のボランティアに実施した。要約すると、左上腕の皮膚のエリアに、2.5%のリドカインの局所適用により麻酔をした。この範囲を70%のイソプロパノールで消毒し、全層皮膚の生検を直径1.5mmのパンチを用いて実施した。組織を、リン酸緩衝食塩水(PBS)ですすぎ、250μLのTrypLE(商標)Select CTS(商標)(Life Technologies Corporation)を含有する1.5mLの管に入れ、30分間37Cでインキュベートした。次に、組織を、250μLのDMEM/F12-CTS(商標)(Life Technologies Corporation)+5mg/mLのコラゲナーゼを含有する1.5mL管へ移し、2時間37Cでインキュベートした。表皮を、ピンセットを用いて除去し、組織を機械的に解離させた。細胞を、DMEM/F12-CTS(商標)で2回すすぎ、24ウェル及び96ウェルプレートのフィブロネクチンでコーティングされたウェルにプレーティングした。さらに、瀉血を同じボランティアに実施し、静脈血をVacutainer(登録商標)SST(商標)管(Becton、Dickinson and Company)に収集した。血清を、製造者のプロトコルにしたがって分離した。同質遺伝子プレーティング培地を、DMEM/F12-CTS(商標)+2mMのL-アラニル-L-グルタミン(Sigma-Aldrich Co.LLC.)+20%のヒト血清を混合することにより調製した。皮膚組織試料由来の細胞を、トランスフェクション培地または同質遺伝子プレーティング培地のいずれかにプレーティングした。2日後、ウェルをすすぎ、培地をトランスフェクション培地と交換した。線維芽細胞形態を有する多数の細胞が、2日目までに付着し、広がり始めた。2日目から、細胞を、全量がより小さいウェルに適応させるように減らされた状態で、実施例1にしたがって合成したRNAで、実施例2にしたがってトランスフェクションした。5日目までに、リプログラミングに合致する形態を有する細胞のエリアが、観察された。
初代ヒト線維芽細胞を、20,000細胞/ウェルの密度で、トランスフェクション培地の、組換えヒトフィブロネクチン及び組換えヒトビトロネクチン(それぞれを、DMEM/F12中で1μg/mL、1mL/ウェルの濃度まで希釈し、1時間室温でインキュベートした)でコーティングされた6ウェルプレートにプレーティングした。翌日、細胞を、RNAの用量が1日目に0.5μg/ウェル、2日目に0.5μg/ウェル、及び3日目に2μg/ウェルであることを除いて、実施例1にしたがって合成されたRNAで、実施例2のようにトランスフェクションした。画像を4日目に撮影した。リプログラミングに合致する形態を示す細胞の小さなコロニーが、4日目に見えた。
初代ヒト線維芽細胞を、20,000細胞/ウェルの密度で、トランスフェクション培地の、組換えヒトフィブロネクチン及び組換えヒトビトロネクチン(それぞれを、DMEM/F12中で1μg/mL、1mL/ウェルの濃度まで希釈し、1時間室温でインキュベートした)でコーティングされた6ウェルプレートにプレーティングした。翌日、細胞を、RNAの用量が1日目に0.5μg/ウェル、2日目に0.5μg/ウェル、3日目に2μg/ウェル、4日目に2μg/ウェル、及び5日目に4μg/ウェルであることを除いて、実施例1にしたがって合成されたRNAで、実施例2のようにトランスフェクションした。リプログラミングに合致する形態を示す細胞の小さなコロニーが、早くも5日目には見えるようになった。7日目に、培地を、DMEM/F12+20%Knockout(商標)Serum Replacement(Life Technologies Corporation)+1X非必須アミノ酸+2mMのL-グルタミンと交換し、24時間、照射したマウス胚性線維芽細胞で馴化し、次に20ng/mLのbFGF及び10μMのY-27632を補充した。リプログラミングされた形態を有する大きなコロニーが、早くも8日目には見えるようになった。コロニーを10日目に採取し、基底膜抽出物(Cultrex(登録商標)Human BME Pathclear(登録商標)、Trevigen Inc.)でコーティングされたウェルにプレーティングした。細胞は急速に成長し、継代されて株を樹立した。
初代ヒト新生児線維芽細胞を、10,000細胞/ウェルの密度で、トランスフェクション培地の、組換えヒトフィブロネクチン及び組換えヒトビトロネクチン(それぞれを、DMEM/F12中で1μg/mL、1mL/ウェルの濃度まで希釈し、1時間室温でインキュベートした)でコーティングされた6ウェルプレートにプレーティングした。翌日、細胞を、A、0.5の7dG、0.5の5mU、及び5mCを含有するRNA、ならびに1日目に0.5μg/ウェル、2日目に0.5μg/ウェル、3日目に2μg/ウェル、4日目に2μg/ウェル、及び5日目に4μg/ウェルのRNA用量を用いて、実施例2のようにトランスフェクションした。リプログラミングに合致する形態を示す細胞の小さなコロニーが、早くも5日目には見えるようになった。6日目に、培地を維持培地と交換した。細胞を、Oct4に対する抗体を用いて染色した。リプログラミングに合致する形態を示す細胞のOct4陽性コロニーが、ウェル全体のいたるところで見えた。
6ウェルプレートのウェルを、室温で1時間、組換えヒトフィブロネクチン及び組換えヒトビトロネクチンの混合物(DMEM/F12中で1μg/mL、1mL/ウェル)でコーティングした。初代成人ヒト線維芽細胞を、10,000細胞/ウェルの密度で、トランスフェクション培地の、コーティングされたウェルにプレーティングした。細胞を、5%のCO2及び5%のO2、37Cに維持した。翌日から、細胞を、実施例1したがって合成されたRNAで、5日間毎日、実施例2にしたがってトランスフェクションした。5日間の各日にトランスフェクションされたRNAの総量は、それぞれ、0.5μg、0.5μg、2μg、2μg、及び4μgであった。4回目のトランスフェクションから、培地を1日に2回交換した。最終のトランスフェクションの翌日に、培地を、10μMのY-27632が補充されたトランスフェクション培地と交換した。あるいは、各日にトランスフェクションされたRNAの総量は、それぞれ0.25μg、0、0.5μg、0.5μg、及び0.5μg、または0.25μg、0、0.25μg、0.25μg、0.25μg、及び0.25μgであった。ある特定の実験では、トランスフェクション培地を、トランスフェクション時に1日に1回だけ交換した。リプログラミングされた形態を有するコンパクトなコロニーが、4日目までにトランスフェクションされた各ウェルで見えるようになった。
全層皮膚のパンチ生検を、承認されたプロトコルにしたがって、健康な31歳のボランティアに実施した。要約すると、左上腕の皮膚のエリアに、2.5%のリドカインの局所適用により麻酔をした。この範囲を70%のイソプロパノールで消毒し、全層皮膚の生検を直径1.5mmのパンチを用いて実施した。組織を、リン酸緩衝食塩水(PBS)ですすぎ、250μLのTrypLE Select CTS(Life Technologies Corporation)を含有する1.5mLの管に入れ、30分間37Cでインキュベートした。次に、組織を、250μLのDMEM/F12-CTS(Life Technologies Corporation)+5mg/mLのコラゲナーゼを含有する1.5mL管へ移し、2時間37Cでインキュベートした。表皮を、ピンセットを用いて除去し、組織を機械的に解離させた。細胞を、DMEM/F12-CTSで2回すすいだ。さらに、瀉血を同じボランティアに実施し、静脈血をVacutainer SST管(Becton、Dickinson and Company)に収集した。血清を、製造者の指示にしたがって分離した。同質遺伝子プレーティング培地を、DMEM/F12-CTS+2mMのL-アラニル-L-グルタミン(Sigma-Aldrich Co.LLC.)+20%のヒト血清を混合することにより調製した。皮膚組織試料由来の細胞を、同質遺伝子プレーティング培地の、6ウェルプレートのフィブロネクチンでコーティングされたウェルにプレーティングした。線維芽細胞形態を有する多数の細胞が、2日目までに付着し、広がり始めた。細胞を拡張させ、Synth-a-Freeze(Life Technologies Corporation)で凍結させた。
初代ヒト線維芽細胞を、実施例19のようにプレーティングした。翌日、細胞を、実施例1したがって合成されたRNAで、実施例2のようにトランスフェクションした。翌日、ウェルのうちの1つの中の細胞を、2回目にトランスフェクションした。2回目のトランスフェクションの2日後に、遺伝子編集の効率を、変異特異的ヌクレアーゼアッセイを用いて測定した。
6ウェルプレートでのトランスフェクションのために、1μgのヒトAPP遺伝子のエクソン16を標的とする遺伝子編集タンパク質をコードするRNA、1μgの標的細胞に存在しなかったPstI制限部位を含有する一本鎖修復テンプレートDNA、及び6μLのトランスフェクション試薬(Lipofectamine RNAiMAX、Life Technologies Corporation)を、まず、複合体形成培地(Opti-MEM、Life Technologies Corporation)で別々に希釈して、120μLの総量にした。次に、希釈されたRNA、修復テンプレート、及びトランスフェクション試薬を、トランスフェクション試薬の製造者の指示にしたがって、混合し、室温で15分間インキュベートした。複合体を、培養中の細胞に添加した。約120μLの複合体を、1ウェル当たり2mLのトランスフェクション培地を既に含有していた6ウェルプレートの各ウェルに添加した。プレートを穏やかに振盪して、複合体をウェル全体に分配させた。細胞を4時間から一晩、複合体とインキュベートした後、培地を新しいトランスフェクション培地(2mL/ウェル)と交換した。翌日、培地をDMEM+10%のFBSに交換した。トランスフェクションの2日後、ゲノムDNAを分離及び精製した。APP遺伝子内の領域をPCRにより増幅し、増幅された産物を、PstIで消化し、ゲル電気泳動により分析した。
40匹の雌のNCr nu/nuマウスに、50%のマトリゲル(BD Biosciences)中の5×106のMDA-MB-231腫瘍細胞を皮下注入した。細胞注入量は、0.2mL/マウスであった。試験開始時のマウスの週齢は、8~12週であった。腫瘍が100~150mm3の平均サイズに達した時に、ペアマッチを行い、動物をそれぞれ10匹ずつの4つのグループに分け、処置を開始した。体重を、初めの5日間は毎日、その後試験の終了までは隔週で測定した。処置は、ビヒクル(Lipofectamine 2000、Life Technologies Corporation)と複合したRiboSlice BIRC5-1.2で構成された。各グループに対する投与溶液を調製するために、308μLの複合体形成緩衝液(Opti-MEM、Life Technologies Corporation)を、2つの滅菌RNaseフリーの1.5mLの管のそれぞれにピペッティングした。22μLのRiboSlice BIRC5-1.2(500ng/μL)を、2つの管のうちの1つに添加し、管の内容物をピペッティングにより混合した。22μLのビヒクルを、第2の管に添加した。第2の管の内容物を混合し、次に第1の管に移し、ピペッティングにより第1の管の内容物と混合し、複合体を形成した。複合体を、10分間室温でインキュベートした。インキュベーションの間、シリンジを装填した。動物に、動物1匹当たり60μLの総量で、動物1匹当たり1μgのRNAの総用量で、静脈内または腫瘍内注入した。合計5回の処置を、注入が1日おきに実施される状態で施された。用量は、体重に対して調整されなかった。動物を、17日間観察した。平均体重に著しい減少は観察されず、RiboSlice遺伝子編集RNAのインビボの安全性が実証された。
ポリエチレンイミン(PEI)、種々の商用の脂質系トランスフェクション試薬、ペプチド系トランスフェクション試薬(N-TER、Sigma-Aldrich Co.LLC.)、ならびにいくつかの脂質系及びステロール系送達試薬を含む送達試薬を、インビトロでのトランスフェクション効率及び毒性についてスクリーニングした。送達試薬を、RiboSlice BIRC5-1.2と複合し、複合体を培養中のHeLa細胞に送達した。毒性を、トランスフェクションの24時間後に細胞密度を分析することにより査定した。トランスフェクション効率を、形態学的変化を分析することにより評価した。試験された試薬は、広範囲の毒性及びトランスフェクション効率を示した。より高い割合のエステル結合を含有する試薬は、より低い割合のエステル結合を含有する試薬またはエステル結合を含有しない試薬よりも低い毒性を示した。
500ng/μLのRNA1μgを3μLの複合体形成培地(Opti-MEM、Life Technologies Corporation)と混合し、RNA1μg当たり2.5μLのトランスフェクション試薬(Lipofectamine 2000、Life Technologies Corporation)を2.5μLの複合体形成培地と混合することにより、高濃度リポソームRiboSliceを調製した。次に、希釈したRNA及びトランスフェクション試薬を、混合し、室温で10分間インキュベートして、高濃度リポソームRiboSliceを形成した。あるいは、DOSPAまたはDOSPERを含有するトランスフェクション試薬が用いられる。
40匹の雌のNCr nu/nuマウスに、1×107のU-251腫瘍細胞を皮下注入した。細胞注入量は、0.2mL/マウスであった。試験開始時のマウスの週齢は、8~12週であった。腫瘍が35~50mm3の平均サイズに達した時に、ペアマッチを行い、動物をそれぞれ10匹ずつの4つのグループに分け、治療を開始した。体重を、初めの5日間は毎日、その後試験の終了までは隔週で測定した。キャリパー測定を隔週で行い、腫瘍サイズを算出した。治療は、ビヒクル(Lipofectamine 2000、Life Technologies Corporation)と複合したRiboSlice BIRC5-1.2で構成された。投与溶液を調製するために、294μLの複合体形成緩衝液(Opti-MEM、Life Technologies Corporation)を、196μLのRiboSlice BIRC5-1.2(500ng/μL)を含有する管にピペッティングし、管の内容物をピペッティングにより混合した。245μLの複合体形成緩衝液を、245μLのビヒクルを含有する管にピペッティングした。第2の管の内容物を混合し、次に第1の管に移し、ピペッティングにより第1の管の内容物と混合し、複合体を形成した。複合体を、10分間室温でインキュベートした。インキュベーションの間、シリンジを装填した。動物に、動物1匹当たり2μgまたは5μgのRNAの総用量のいずれかで、動物1匹当たり20μLまたは50μLの総量のいずれかで、腫瘍内注入した。合計5回の治療は、注入が1日おきに実施される状態で施された。用量は、体重に対して調整されなかった。動物を、25日間観察した。
リポソームを、次の配合物:3.2mg/mLのN-(カルボニル-エトキシポリエチレングリコール2000)-1,2-ジステアロイル-sn-グリセロ-3-フォスフォエタノールアミン(MPEG2000-DSPE)、9.6mg/mLの完全水素化フォスファチジルコリン、3.2mg/mLのコレステロール、2mg/mLのアンモニウムスルフェート、及び緩衝液としてのヒスチジンを用いて調製する。pHを、水酸化ナトリウムを用いて制御し、等張性を、ショ糖を用いて維持する。リポソームを形成するため、脂質を、有機溶媒中で混合し、乾燥させ、撹拌しながら水和させ、800nmの平均孔径を有するポリカーボネートフィルターを通して押出すことにより寸法決めをする。核酸を、核酸1μg当たり10μgのリポソーム配合物を組み合わせ、5分間室温でインキュベートすることによりカプセル化する。
リポソームを、0.27mg/mLの1,2-ジステアロイル-sn-グリセロ-3-フォスフォエタノールアミン-N-[葉酸(ポリエチレングリコール)-5000](FA-MPEG5000-DSPE)を脂質混合物に添加することを除いて、実施例62にしたがって調製する。
実施例1にしたがって合成された治療用タンパク質をコードする合成RNAをカプセル化するリポソームを、実施例27または実施例28にしたがって調製する。リポソームを、注入または静脈内注入により投与する。
全RNAを、製造業者の指示にしたがって、RNeasyミニキット(QIAGEN GmbH)を用いて、ヒト新生児皮膚線維芽細胞から抽出した。ヒトエラスチンをコードするcDNAを、MonsterScript(商標)逆転写酵素(Epicentre Biotechnologies)及びプライマーAAAAAAACCGGTTCATTTTCTCTTCCGGCCACを用いて調製した。インビトロ転写(ivT)テンプレートを、プライマーF:AAAAAAGCTAGCATGGCGGGTCTGACG、及びR:AAAAAAACCGGTTCATTTTCTCTTCCGGCCACを用いて、エラスチンコード配列(CDS)のPCR増幅によりcDNAから調製した。次に、PCR産物を、アガロースゲル電気泳動及びQIAquickゲル抽出キット(QIAGEN GmbH)を用いることにより精製し、ヒトβグロビン(HBB)5′及び3′非翻訳領域ならびに強いコザック配列を含有するベクターにクローニングした。ベクターを、RNA合成に先立って増幅させ、精製し、線形化させた。
ヒトエラスチンをコードするRNAを、製造者の指示にしたがって、実施例30のDNAテンプレート及びT7高収率RNA合成キット(New England Biolabs,Inc.)を用いて合成した(表4)。RNAの試料を、アガロースゲル電気泳動により分析して、RNAの品質を評価した(図1)。次に、RNAを、200ng/μLまで希釈し、RNAse阻害剤(Superase・In(商標)、Life Technologies Corporation)を、RNA200μg当たり1μLの濃度で添加した。RNA溶液を、4℃で保存した。
10%のHSA溶液を、16mMのオクタン酸ナトリウム(Sigma-Aldrich Co.LLC)とプレインキュベートし、完全培地の構築前の3時間に37℃でインキュベートした。
核酸のインビボ送達のための配合物を、好適な緩衝液(例えば、DMEM/F12、複合体形成培地、Opti-MEMなど)中で、実施例31にしたがって合成されたRNA及び実施例8、9、及び/または32にしたがって処理されたヒト血清アルブミンを組み合わせることにより調製する。
実施例33の配合物を、28ゲージ0.5インチの針を有するインスリンシリンジに装填し、表皮を通って患者の真皮に送達する。追加の用量を、必要に応じて投与する。
実施例33の配合物を、約0.1mmの侵入深度に設定された電動マイクロニードルアレイのチャンバに装填する。マイクロニードルアレイは、表皮を通して患者の真皮に配合物を送達する。
実施例33の配合物を、I型及び/またはIII型ヒトコラーゲンをコードするRNAを用いて調製する。配合物を、実施例34または35のように送達する。
実施例33の配合物を、骨格αアクチンをコードするRNAを用いて調製する。配合物を、筋肉注入で患者に送達する。
実施例33の配合物を、塩基性線維芽細胞増殖因子をコードするRNAを用いて調製する。配合物を、実施例34または35のように送達する。
実施例33の配合物を、コラゲナーゼをコードするRNAを用いて調製する。配合物を、実施例34または35のように送達する。
全RNAを、製造業者の指示にしたがって、RNeasyミニキット(QIAGEN GmbH)を用いて、ヒト表皮メラノサイトから抽出した。ヒトチロシナーゼをコードするcDNAを、MonsterScript(商標)逆転写酵素(Epicentre Biotechnologies)を用いて調製した。インビトロ転写(ivT)テンプレートを、チロシナーゼコード配列(CDS)のPCR増幅によりcDNAから調製した。次に、PCR産物を、アガロースゲル電気泳動及びQIAquickゲル抽出キット(QIAGEN GmbH)を用いることにより精製し、ヒトβグロビン(HBB)5′及び3′非翻訳領域ならびに強いコザック配列を含有するベクターにクローニングした。ベクターを、RNA合成に先立って増幅させ、精製し、線形化させた。
ヒトチロシナーゼをコードするRNAを、製造者の指示にしたがって、実施例40のDNAテンプレート及びT7高収率RNA合成キット(New England Biolabs,Inc.)を用いて実施例1にしたがって合成した(表4)。RNAの試料を、アガロースゲル電気泳動により分析して、RNAの品質を評価した。次に、RNAを1μg/μLまで希釈した。RNA溶液を、4℃で保存した。
10%のHSA溶液を、16mMのオクタン酸ナトリウム(Sigma-Aldrich Co.LLC)とプレインキュベートし、完全培地の構築前の3時間に37℃でインキュベートした。
実施例41のRNAを、シリンジに装填し、約30秒間にわたって健康な33歳の男性患者の腹側前腕の真皮に送達した。
実施例43で治療された皮膚のエリアを、コンデンサーに電気的に接続された2電極アレイを用いて、10V~155V及び約10ミリ秒~約1秒の電気パルスに曝露した。患者は、全ての電圧と侵入深度で打診痛知覚を報告した。処置範囲が、24~48時間後に黒くなった(図16を参照のこと)。実験を、同様の結果で数回繰り返した。
実施例41のRNAまたは実施例29のリポソームを、角質層の破壊を伴ってまたは伴わずに皮膚に直接適用し、または平方センチメートル当たり1マイクログラム以下の用量を用いて皮内注入する。任意に、電場を、RNAの送達を増強するために、実施例44のように、または表面接触パッチを用いて適用する。
エラスチンをコードするRNAを、実施例1にしたがって調製する。RNAを、実施例43、44、または45のように送達する。
コラーゲンをコードするRNAを、実施例1にしたがって調製する。RNAを、実施例43、44、または45のように送達する。
ダルベポエチンαをコードするRNAを、実施例1にしたがって調整した。RNAを、実施例43、44、または45のように送達する。
アクチンをコードするRNAを、実施例1にしたがって調製する。RNAを、実施例43、44、または45のように電場を用いて、または用いずに筋肉注射で患者に送達する。
塩基性線維芽細胞増殖因子をコードするRNAを、実施例1にしたがって調製する。RNAを、実施例43、44、または45のように送達する。
コラゲナーゼをコードするRNAを、実施例1にしたがって調製する。RNAを、実施例43、44、または45のように送達する。
ボツリヌス毒素をコードするRNAを、実施例1にしたがってを調製する。RNAを、実施例43、44、または45のように送達する。
ヒトCOL1A1遺伝子のコード配列を含むRNAを、実施例1にしたがって合成した。初代ヒト皮膚線維芽細胞を、24ウェルプレートにプレーティングし、実施例2にしたがってトランスフェクションした。トランスフェクションの24~72時間後に、細胞を、コラーゲンIを標的とする抗体を用いて固定及び染色した。コラーゲンの多くの細胞外沈着物が、トランスフェクションされたウェル中で見えた(図17)。
ヒトCOL7遺伝子のコード配列を含むRNAを、実施例1にしたがって合成した。初代ヒト皮膚線維芽細胞を、24ウェルプレートにプレーティングし、実施例2にしたがってトランスフェクションした。トランスフェクションの24~72時間後に、細胞を、コラーゲンVIIを標的とする抗体を用いて固定及び染色した。トランスフェクションされた細胞は、トランスフェクションされていない対照と比較して、高濃度のコラーゲンVIIを示した(図18)。
ヒトCOL1A1遺伝子またはヒトCOL7遺伝子のコード配列を含むRNAを、実施例1にしたがって合成した。RNAをシリンジに装填し、約30秒にわたって、または実施例43、44、もしくは45のように患者の真皮に送達する。
実施例55で処置された皮膚の範囲を、電源に電気的に接続された多電極アレイを用いて、10V~155V及び約50マイクロ秒~約1秒の電気パルスに曝露する。
当業者は、日常の実験のみを用いて、本明細書に具体的に記載されるある特定の実施形態に対する多数の均等物を認識し、または確認することができるであろう。かかる均等物は、次の特許請求の範囲に包含されることが意図される。
本明細書で参照される全ての特許及び出版物は、全体として参照により本明細書に組み込まれる。
Claims (7)
- 合成RNA分子と脂質ビヒクルとを含む脂質-RNA複合体を含む、ケラチノサイトのCOL7遺伝子をインビトロで編集するための組成物であって、
前記合成RNAがCOL7遺伝子を標的とする遺伝子編集タンパク質をコードしており、前記遺伝子編集タンパク質がCOL7遺伝子を編集し、前記遺伝子編集タンパク質がDNA結合ドメイン及びヌクレアーゼドメインを含み、前記遺伝子編集タンパク質が前記ケラチノサイトのCOL7遺伝子において一本鎖切断又は二本鎖切断をもたらす、組成物。 - 前記遺伝子編集タンパク質が、配列番号78のアミノ酸配列をコードする核酸配列を標的とすることができる、請求項1に記載の組成物。
- 前記遺伝子編集タンパク質が、ヌクレアーゼ、転写活性化因子様エフェクターヌクレアーゼ(TALEN)、ジンクフィンガーヌクレアーゼ、メガヌクレアーゼ、ニッカーゼ、及び規則的な間隔をもってクラスター化された短鎖回文反復(clustered regularly interspaced short palindromic repeat)(CRISPR)結合タンパク質から成る群から選択される、請求項1に記載の組成物。
- 前記合成RNAの分子が更に、5’キャップ、5’キャップ1構造及び3’ポリ(A)テールのうちの1又は複数を含む、請求項1に記載の組成物。
- 前記合成RNA分子が、5’キャップ1構造と3’ポリ(A)テールの両方を含む、請求項1に記載の組成物。
- 前記脂質ビヒクルが脂質又は脂質様物質である、請求項1に記載の組成物。
- 前記DNA結合ドメインと前記ヌクレアーゼドメインがリンカーにより隔てられている、請求項1に記載の組成物。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2023026873A JP2023075165A (ja) | 2014-01-31 | 2023-02-24 | 核酸生成及び送達のための方法及び製品 |
Applications Claiming Priority (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201461934397P | 2014-01-31 | 2014-01-31 | |
US61/934,397 | 2014-01-31 | ||
US201462038608P | 2014-08-18 | 2014-08-18 | |
US62/038,608 | 2014-08-18 | ||
US201462069667P | 2014-10-28 | 2014-10-28 | |
US62/069,667 | 2014-10-28 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016533700A Division JP2017510542A (ja) | 2014-01-31 | 2015-01-30 | 核酸生成及び送達のための方法及び製品 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2023026873A Division JP2023075165A (ja) | 2014-01-31 | 2023-02-24 | 核酸生成及び送達のための方法及び製品 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2020193203A JP2020193203A (ja) | 2020-12-03 |
JP7235702B2 true JP7235702B2 (ja) | 2023-03-08 |
Family
ID=53757787
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016533700A Pending JP2017510542A (ja) | 2014-01-31 | 2015-01-30 | 核酸生成及び送達のための方法及び製品 |
JP2020128881A Active JP7235702B2 (ja) | 2014-01-31 | 2020-07-30 | 核酸生成及び送達のための方法及び製品 |
JP2023026873A Pending JP2023075165A (ja) | 2014-01-31 | 2023-02-24 | 核酸生成及び送達のための方法及び製品 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016533700A Pending JP2017510542A (ja) | 2014-01-31 | 2015-01-30 | 核酸生成及び送達のための方法及び製品 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2023026873A Pending JP2023075165A (ja) | 2014-01-31 | 2023-02-24 | 核酸生成及び送達のための方法及び製品 |
Country Status (14)
Country | Link |
---|---|
US (4) | US9770489B2 (ja) |
EP (3) | EP4249036A3 (ja) |
JP (3) | JP2017510542A (ja) |
KR (2) | KR20220100078A (ja) |
CN (1) | CN105940110A (ja) |
AU (3) | AU2015210769B2 (ja) |
BR (1) | BR112016017736A2 (ja) |
CA (1) | CA2937036A1 (ja) |
DK (1) | DK3690056T5 (ja) |
ES (2) | ES2787198T3 (ja) |
FI (1) | FI3690056T3 (ja) |
MX (2) | MX2016009771A (ja) |
RU (2) | RU2714404C2 (ja) |
WO (1) | WO2015117021A1 (ja) |
Families Citing this family (64)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2012333134B2 (en) | 2011-07-22 | 2017-05-25 | John Paul Guilinger | Evaluation and improvement of nuclease cleavage specificity |
US9163284B2 (en) | 2013-08-09 | 2015-10-20 | President And Fellows Of Harvard College | Methods for identifying a target site of a Cas9 nuclease |
US9359599B2 (en) | 2013-08-22 | 2016-06-07 | President And Fellows Of Harvard College | Engineered transcription activator-like effector (TALE) domains and uses thereof |
US9340800B2 (en) | 2013-09-06 | 2016-05-17 | President And Fellows Of Harvard College | Extended DNA-sensing GRNAS |
US9737604B2 (en) | 2013-09-06 | 2017-08-22 | President And Fellows Of Harvard College | Use of cationic lipids to deliver CAS9 |
US9388430B2 (en) | 2013-09-06 | 2016-07-12 | President And Fellows Of Harvard College | Cas9-recombinase fusion proteins and uses thereof |
US9068179B1 (en) | 2013-12-12 | 2015-06-30 | President And Fellows Of Harvard College | Methods for correcting presenilin point mutations |
AU2015298571B2 (en) | 2014-07-30 | 2020-09-03 | President And Fellows Of Harvard College | Cas9 proteins including ligand-dependent inteins |
WO2016070166A2 (en) | 2014-11-02 | 2016-05-06 | Arcturus Therapeutics, Inc. | Messenger una molecules and uses thereof |
AU2016218977C1 (en) * | 2015-02-13 | 2023-03-23 | Factor Bioscience Inc. | Nucleic acid products and methods of administration thereof |
WO2017070632A2 (en) | 2015-10-23 | 2017-04-27 | President And Fellows Of Harvard College | Nucleobase editors and uses thereof |
US11459560B2 (en) | 2015-11-23 | 2022-10-04 | The Regents Of The University Of Colorado | Methods and compositions for reprogramming cells |
EP3712273A1 (en) * | 2016-04-08 | 2020-09-23 | Krystal Biotech, LLC | Compositions for the treatment of wounds, disorders, and diseases of the skin |
EP3241905A1 (en) * | 2016-05-06 | 2017-11-08 | Miltenyi Biotec GmbH | Method for introducing nucleic acids into a cell |
WO2017197141A2 (en) * | 2016-05-13 | 2017-11-16 | Sangamo Therapeutics, Inc. | Targeted treatment of androgenic alopecia |
JP7183041B2 (ja) * | 2016-06-29 | 2022-12-05 | センジュ ユーエスエー、インコーポレイテッド | 経皮薬物送達システムおよびその使用方法 |
CA3032699A1 (en) | 2016-08-03 | 2018-02-08 | President And Fellows Of Harvard College | Adenosine nucleobase editors and uses thereof |
WO2018031683A1 (en) | 2016-08-09 | 2018-02-15 | President And Fellows Of Harvard College | Programmable cas9-recombinase fusion proteins and uses thereof |
WO2018035377A1 (en) | 2016-08-17 | 2018-02-22 | Factor Bioscience Inc. | Nucleic acid products and methods of administration thereof |
WO2018039438A1 (en) | 2016-08-24 | 2018-03-01 | President And Fellows Of Harvard College | Incorporation of unnatural amino acids into proteins using base editing |
EP3526320A1 (en) | 2016-10-14 | 2019-08-21 | President and Fellows of Harvard College | Aav delivery of nucleobase editors |
EP3526233A4 (en) * | 2016-10-14 | 2020-03-18 | Neomatrix Therapeutics, Inc | PEPTIDES DERIVED FROM FIBRONECTIN WITH IMPROVED BIOACTIVITY AND REDUCED SENSITIVITY TO NEUTROPHILIC ELASTASE DEGRADATION |
US11464836B2 (en) | 2016-12-08 | 2022-10-11 | Curevac Ag | RNA for treatment or prophylaxis of a liver disease |
US10745677B2 (en) | 2016-12-23 | 2020-08-18 | President And Fellows Of Harvard College | Editing of CCR5 receptor gene to protect against HIV infection |
EP3592853A1 (en) | 2017-03-09 | 2020-01-15 | President and Fellows of Harvard College | Suppression of pain by gene editing |
JP2020510439A (ja) | 2017-03-10 | 2020-04-09 | プレジデント アンド フェローズ オブ ハーバード カレッジ | シトシンからグアニンへの塩基編集因子 |
KR102687373B1 (ko) | 2017-03-23 | 2024-07-23 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | 핵산 프로그램가능한 dna 결합 단백질을 포함하는 핵염기 편집제 |
WO2018178215A1 (en) | 2017-03-31 | 2018-10-04 | Accanis Biotech F&E Gmbh & Co Kg | Prevention and treatment of non-melanoma skin cancer (nmsc) |
CN107400635A (zh) * | 2017-04-27 | 2017-11-28 | 广州弘宝元生物科技有限公司 | 导入α‑MSH多肽的粘红酵母重组菌株及其制备方法和应用 |
WO2018209320A1 (en) | 2017-05-12 | 2018-11-15 | President And Fellows Of Harvard College | Aptazyme-embedded guide rnas for use with crispr-cas9 in genome editing and transcriptional activation |
KR20200018645A (ko) | 2017-06-15 | 2020-02-19 | 더 리전트 오브 더 유니버시티 오브 캘리포니아 | 표적화된 비-바이러스 dna 삽입 |
EP3658573A1 (en) | 2017-07-28 | 2020-06-03 | President and Fellows of Harvard College | Methods and compositions for evolving base editors using phage-assisted continuous evolution (pace) |
EP3437650A1 (en) * | 2017-07-31 | 2019-02-06 | Accanis Biotech F&E GmbH & Co KG | Treatment of local skin hypotrophy conditions |
BR102017016440A2 (pt) | 2017-07-31 | 2019-03-19 | Universidade Federal Do Rio Grande Do Sul | Composição para terapia gênica do sistema nervoso central, processo de obtenção e uso da mesma |
WO2019139645A2 (en) | 2017-08-30 | 2019-07-18 | President And Fellows Of Harvard College | High efficiency base editors comprising gam |
JP2020536499A (ja) * | 2017-09-05 | 2020-12-17 | アジトラ インコーポレーテッド | 組換え微生物を用いて炎症性皮膚疾患を処置するための方法および組成物 |
SG11202003229RA (en) * | 2017-10-11 | 2020-05-28 | Illustris Pharmaceuticals Inc | Methods and compositions for topical delivery |
CN111757937A (zh) | 2017-10-16 | 2020-10-09 | 布罗德研究所股份有限公司 | 腺苷碱基编辑器的用途 |
BR112020008201A2 (pt) | 2017-10-27 | 2020-10-06 | The Regents Of The University Of California | substituição-alvo de receptores de células t endógenos |
EP3543351B1 (en) | 2018-03-19 | 2022-08-10 | Ricoh Company, Ltd. | Nucleic acid sample-contained container, method for producing nucleic acid sample-contained container, and nucleic acid sample |
CA3096081A1 (en) * | 2018-04-05 | 2019-10-10 | Azitra Inc | Methods and compositions for treating skin disease with recombinant microorganisms |
CA3094345A1 (en) | 2018-04-12 | 2019-10-17 | Krystal Biotech, Inc. | Compositions and methods for the treatment of autosomal recessive congenital ichthyosis |
US10786438B2 (en) * | 2018-04-27 | 2020-09-29 | Krystal Biotech, Inc. | Recombinant nucleic acids encoding cosmetic protein(s) for aesthetic applications |
CN112867792A (zh) | 2018-08-23 | 2021-05-28 | 桑格摩生物治疗股份有限公司 | 工程化靶特异性碱基编辑器 |
WO2020068862A1 (en) | 2018-09-24 | 2020-04-02 | Krystal Biotech, Inc. | Compositions and methods for the treatment of netherton syndrome |
AU2019346461A1 (en) * | 2018-09-26 | 2021-04-15 | Krystal Biotech, Inc. | Compositions and methods for the treatment of skin diseases |
US20220034872A1 (en) * | 2018-10-31 | 2022-02-03 | National Cancer Center | Composition comprising material for regulating oct4 modification to repress stemness |
WO2020163703A1 (en) | 2019-02-08 | 2020-08-13 | Krystal Biotech, Inc. | Compositions and methods for delivering cftr polypeptides |
WO2020191249A1 (en) | 2019-03-19 | 2020-09-24 | The Broad Institute, Inc. | Methods and compositions for editing nucleotide sequences |
US20210000910A1 (en) | 2019-07-03 | 2021-01-07 | Jysk Skin Solutions Pte Ltd | Topical compositions |
US10501404B1 (en) | 2019-07-30 | 2019-12-10 | Factor Bioscience Inc. | Cationic lipids and transfection methods |
CN110467667B (zh) * | 2019-09-03 | 2020-11-24 | 中国科学院理化技术研究所 | 一种抗肿瘤活性肽及其应用 |
MX2022014008A (es) | 2020-05-08 | 2023-02-09 | Broad Inst Inc | Métodos y composiciones para la edición simultánea de ambas cadenas de una secuencia de nucleótidos de doble cadena objetivo. |
CN114717229B (zh) * | 2021-01-05 | 2024-09-10 | 麦塞拿治疗(香港)有限公司 | 治疗性mRNA的无细胞和无载体体外RNA转录方法和核酸分子 |
US11779660B2 (en) | 2021-04-02 | 2023-10-10 | Krystal Biotech, Inc. | Viral vectors for cancer therapy |
CA3231676A1 (en) * | 2021-09-08 | 2023-03-16 | Flagship Pioneering Innovations Vi, Llc | Methods and compositions for modulating a genome |
KR20240099259A (ko) | 2021-10-14 | 2024-06-28 | 아스널 바이오사이언시스, 인크. | 공동 발현된 shrna 및 논리 게이트 시스템을 갖는 면역 세포 |
CN114150022B (zh) * | 2021-12-06 | 2023-08-22 | 中国科学院精密测量科学与技术创新研究院 | 一种基于植物微纳结构的生化分子细胞递送方法及应用 |
JP7271026B1 (ja) * | 2021-12-28 | 2023-05-11 | 株式会社Hyperion Drug Discovery | 遺伝子導入細胞の免疫応答を回避させるための剤 |
US20230285546A1 (en) * | 2022-01-05 | 2023-09-14 | Helix Nanotechnologies, Inc. | Compositions comprising alpha-factor prepro sequence and uses thereof |
CN114480365B (zh) * | 2022-01-18 | 2024-05-28 | 南昌大学 | 一种高分子-酶-无机杂化纳米花及其制备方法与其在降解食用油中真菌毒素的应用 |
WO2023191016A1 (ja) * | 2022-03-30 | 2023-10-05 | ヤマサ醤油株式会社 | フィブリリン産生促進剤、化粧料組成物又は皮膚外用剤、経口投与剤、及びエラスチン線維産生促進剤 |
US12083204B2 (en) | 2022-06-02 | 2024-09-10 | L'oreal | Topical composition for homeostatic delivery of nitric oxide and uses thereof |
WO2024158256A1 (ko) * | 2023-01-27 | 2024-08-02 | 주식회사 차메디텍 | 니도겐을 포함하는 피부 상태 개선, 피부 손상 치료 또는 줄기세포능 유지용 조성물 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2013086008A1 (en) | 2011-12-05 | 2013-06-13 | Factor Bioscience Inc. | Methods and products for transfecting cells |
Family Cites Families (120)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3539465A (en) | 1968-10-08 | 1970-11-10 | Ncr Co | Encapsulation of hydrophilic liquid-in-oil emulsions |
US5993434A (en) | 1993-04-01 | 1999-11-30 | Genetronics, Inc. | Method of treatment using electroporation mediated delivery of drugs and genes |
US5843780A (en) | 1995-01-20 | 1998-12-01 | Wisconsin Alumni Research Foundation | Primate embryonic stem cells |
US5711964A (en) | 1995-06-07 | 1998-01-27 | United States Of America | Method for the intracellular delivery of biomolecules using liposomes containing cationic lipids and vitamin D |
US6602693B1 (en) * | 1996-07-03 | 2003-08-05 | Clear Solutions Biotech, Inc. | Gene encoding hyaluronan synthase |
US6770291B2 (en) | 1996-08-30 | 2004-08-03 | The United States Of America As Represented By The Department Of Health And Human Services | Liposome complexes for increased systemic delivery |
JP4203835B2 (ja) | 1996-08-19 | 2009-01-07 | アメリカ合衆国 | 全身への送達を増加させる新規のリポソーム複合体 |
TW520297B (en) | 1996-10-11 | 2003-02-11 | Sequus Pharm Inc | Fusogenic liposome composition and method |
AU5734998A (en) | 1997-01-10 | 1998-08-03 | Life Technologies, Inc. | Embryonic stem cell serum replacement |
US6316260B1 (en) | 1997-08-22 | 2001-11-13 | Bernina Biosystems Gmbh | Tetraether lipid derivatives and liposomes and lipid agglomerates containing tetraether lipid derivatives, and use thereof |
AU9319398A (en) | 1997-09-19 | 1999-04-05 | Sequitur, Inc. | Sense mrna therapy |
ATE462468T1 (de) * | 1999-06-04 | 2010-04-15 | Georgia Tech Res Inst | Vorrichtungen zur vergrösserten penetration von mikronadeln in biologischen hautschichten |
US20110171185A1 (en) | 1999-06-30 | 2011-07-14 | Klimanskaya Irina V | Genetically intact induced pluripotent cells or transdifferentiated cells and methods for the production thereof |
US20020054895A1 (en) | 1999-07-23 | 2002-05-09 | Alwyn Company, Inc. | Allantoin-containing skin cream |
US20020064876A1 (en) * | 1999-12-28 | 2002-05-30 | Kyonggeun Yoon | Novel gene therapy methods for the treatment of skin disorders |
US6595947B1 (en) * | 2000-05-22 | 2003-07-22 | Becton, Dickinson And Company | Topical delivery of vaccines |
KR100865706B1 (ko) | 2000-09-26 | 2008-10-28 | 이데라 파마슈티칼즈, 인코포레이티드 | 화학적인 위치 변화에 의해 면역자극 올리고누클레오티드유사체의 면역자극 활성을 조절하는 방법 |
US7189759B2 (en) | 2001-05-23 | 2007-03-13 | Medicis Pharmaceutical Corporation | Compositions for the treatment of pigmentation disorders and methods for their manufacture |
WO2003018767A2 (en) | 2001-08-27 | 2003-03-06 | Advanced Cell Technology, Inc. | Trans-differentiation and re-differentiation of somatic cells and production of cells for cell therapies |
CA2461185A1 (en) | 2001-09-21 | 2003-04-03 | Japan Science And Technology Corporation | Method of screening reprogramming factor, reprogramming factor screened by the method, method of using the reprogramming factor, method of differentiating undifferentiated fused cells and method of constructing cell, tissues and organs |
WO2003033697A1 (en) | 2001-10-18 | 2003-04-24 | Ixion Biotechnology, Inc. | Conversion of liver stem and progenitor cells to pancreatic functional cells |
US7276489B2 (en) | 2002-10-24 | 2007-10-02 | Idera Pharmaceuticals, Inc. | Modulation of immunostimulatory properties of oligonucleotide-based compounds by optimal presentation of 5′ ends |
GB0202149D0 (en) | 2002-01-30 | 2002-03-20 | Univ Edinburgh | Pluripotency determining factors and uses thereof |
US20030186249A1 (en) * | 2002-04-01 | 2003-10-02 | Zairen Sun | Human TARPP genes and polypeptides |
JP3785508B2 (ja) | 2002-04-15 | 2006-06-14 | 学校法人慶應義塾 | 遺伝子治療における免疫応答を解析できる実験モデルマウス |
US7737182B2 (en) * | 2002-08-09 | 2010-06-15 | Taisho Pharmaceutical Co., Ltd. | Pharmaceuticals for xerosis |
CN1984921B (zh) | 2003-06-03 | 2010-06-16 | Isis药物公司 | 存活蛋白表达的调节 |
CA2546616A1 (en) | 2003-11-21 | 2005-06-09 | Alza Corporation | Gene delivery mediated by liposome-dna complex with cleavable peg surface modification |
US7682828B2 (en) | 2003-11-26 | 2010-03-23 | Whitehead Institute For Biomedical Research | Methods for reprogramming somatic cells |
AU2005282414C1 (en) | 2004-09-08 | 2011-04-07 | Wisconsin Alumni Research Foundation | Culturing human embryonic stem cells |
MX2007002390A (es) | 2004-09-08 | 2007-04-23 | Wisconsin Alumni Res Found | Medio y cultivo de celulas progenitoras embrionarias. |
AU2006272634B2 (en) | 2005-07-26 | 2013-01-24 | Sangamo Therapeutics, Inc. | Targeted integration and expression of exogenous nucleic acid sequences |
US8323666B2 (en) | 2005-08-01 | 2012-12-04 | Allergan, Inc. | Botulinum toxin compositions |
EP4332227A1 (en) | 2005-08-23 | 2024-03-06 | The Trustees of the University of Pennsylvania | Rna containing modified nucleosides and methods of use thereof |
US9012219B2 (en) | 2005-08-23 | 2015-04-21 | The Trustees Of The University Of Pennsylvania | RNA preparations comprising purified modified RNA for reprogramming cells |
EP1962719A4 (en) | 2005-08-29 | 2011-05-04 | Technion Res And Dev Of Foundation Ltd | MEDIA FOR BREEDING STEM CELLS |
BRPI0619794B8 (pt) | 2005-12-13 | 2022-06-14 | Univ Kyoto | Uso de um fator de reprogramação, agente para a preparação de uma célula-tronco pluripotente induzida a partir de uma célula somática e métodos para preparar uma célula- tronco pluripotente induzida método e para preparar uma célula somática e uso de células-tronco pluripotentes induzidas |
US8278104B2 (en) | 2005-12-13 | 2012-10-02 | Kyoto University | Induced pluripotent stem cells produced with Oct3/4, Klf4 and Sox2 |
US8129187B2 (en) | 2005-12-13 | 2012-03-06 | Kyoto University | Somatic cell reprogramming by retroviral vectors encoding Oct3/4. Klf4, c-Myc and Sox2 |
WO2007079886A1 (de) | 2005-12-22 | 2007-07-19 | Csl Behring Gmbh | Oktanoatreduziertes human albumin |
DE102006051516A1 (de) | 2006-10-31 | 2008-05-08 | Curevac Gmbh | (Basen-)modifizierte RNA zur Expressionssteigerung eines Proteins |
GB0623635D0 (en) | 2006-11-27 | 2007-01-03 | Stem Cell Sciences Uk Ltd | Pluripotent cell growth media |
CA2671850A1 (en) | 2006-12-08 | 2008-06-19 | Massachusetts Institute Of Technology | Delivery of nanoparticles and/or agents to cells |
CN101200758A (zh) | 2006-12-15 | 2008-06-18 | 华中科技大学 | 一种检测col7a1基因突变的方法及其用途 |
US10829733B2 (en) | 2007-01-04 | 2020-11-10 | Biolamina Ab | Composition and method for enabling proliferation of pluripotent human stem cells |
US8859229B2 (en) | 2007-02-02 | 2014-10-14 | Yale University | Transient transfection with RNA |
US9249423B2 (en) | 2007-02-02 | 2016-02-02 | Yale University | Method of de-differentiating and re-differentiating somatic cells using RNA |
SG193653A1 (en) | 2007-03-23 | 2013-10-30 | Wisconsin Alumni Res Found | Somatic cell reprogramming |
WO2008124133A1 (en) | 2007-04-07 | 2008-10-16 | Whitehead Institute For Biomedical Research | Reprogramming of somatic cells |
KR101532442B1 (ko) | 2007-12-10 | 2015-06-29 | 고쿠리츠 다이가쿠 호진 교토 다이가쿠 | 효율적인 핵 초기화 방법 |
EP2072618A1 (en) | 2007-12-14 | 2009-06-24 | Johannes Gutenberg-Universität Mainz | Use of RNA for reprogramming somatic cells |
EP2955222B1 (en) | 2008-03-17 | 2018-09-12 | The Scripps Research Institute | Combined chemical and genetic approaches for generation of induced pluripotent stem cells |
US20110045001A1 (en) | 2008-03-28 | 2011-02-24 | Biontex Laboratories Gmbh | Transfection results of non-viral gene delivery systems by influencing of the innate immune system |
WO2009127230A1 (en) | 2008-04-16 | 2009-10-22 | Curevac Gmbh | MODIFIED (m)RNA FOR SUPPRESSING OR AVOIDING AN IMMUNOSTIMULATORY RESPONSE AND IMMUNOSUPPRESSIVE COMPOSITION |
KR101871192B1 (ko) | 2008-06-04 | 2018-06-27 | 후지필름 셀룰러 다이내믹스, 인코포레이티드 | 비-바이러스 접근법을 사용한 iPS 세포의 생산 방법 |
WO2009147400A1 (en) | 2008-06-05 | 2009-12-10 | Iti Scotland Limited | Stem cell culture media and methods |
WO2010008486A2 (en) | 2008-06-24 | 2010-01-21 | Parkinsons Institute | Pluripotent cell lines and methods of use thereof |
US20100184033A1 (en) | 2008-07-16 | 2010-07-22 | West Michael D | Methods to accelerate the isolation of novel cell strains from pluripotent stem cells and cells obtained thereby |
EP2151248A1 (en) | 2008-07-30 | 2010-02-10 | Johann Bauer | Improved pre-mRNA trans-splicing molecule (RTM) molecules and their uses |
WO2010022194A2 (en) | 2008-08-20 | 2010-02-25 | Virxsys Corporation | Compositions and methods for generation of pluripotent stem cells |
SG10201600234PA (en) | 2008-10-24 | 2016-02-26 | Wisconsin Alumni Res Found | Pluripotent Stem Cells Obtained By Non-Viral Reprogramming |
ES2561949T3 (es) | 2008-11-21 | 2016-03-01 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Reprogramación de células hacia un estado pluripotente |
US20110239315A1 (en) | 2009-01-12 | 2011-09-29 | Ulla Bonas | Modular dna-binding domains and methods of use |
EP2206723A1 (en) | 2009-01-12 | 2010-07-14 | Bonas, Ulla | Modular DNA-binding domains |
US20100209404A1 (en) | 2009-02-10 | 2010-08-19 | University Of Dayton | Enhanced method for producing stem-like cells from somatic cells |
US10894944B2 (en) | 2009-04-10 | 2021-01-19 | Monash University | Cell culture media |
US10837020B2 (en) | 2009-04-22 | 2020-11-17 | Massachusetts Institute Of Technology | Innate immune suppression enables repeated delivery of long RNA molecules |
EP2421563B1 (en) | 2009-04-22 | 2017-04-12 | Massachusetts Institute of Technology | Innate immune suppression enables repeated delivery of long rna molecules |
ES2849181T3 (es) | 2009-04-22 | 2021-08-16 | Viacyte Inc | Composiciones celulares derivadas de células reprogramadas desdiferenciadas |
EP2251437B1 (en) | 2009-05-13 | 2013-12-04 | Hannelore Breitenbach-Koller | Method for identifying compounds that control the translational activity of ribosomal proteins in differential mRNA expression |
US8496941B2 (en) | 2009-06-03 | 2013-07-30 | National Institute Of Advanced Industrial Science And Technology | Vectors for generating pluripotent stem cells and methods of producing pluripotent stem cells using the same |
KR101801404B1 (ko) * | 2009-06-16 | 2017-12-20 | 큐알엔에이, 인크. | 콜라겐 유전자에 대한 천연 안티센스 전사체의 억제에 의한 콜라겐 유전자 관련된 질환의 치료 |
EP3581197A1 (de) | 2009-07-31 | 2019-12-18 | ethris GmbH | Rna mit einer kombination aus unmodifizierten und modifizierten nucleotiden zur proteinexpression |
US9295697B2 (en) | 2009-11-04 | 2016-03-29 | Cellular Dynamics International, Inc. | Episomal reprogramming with chemicals |
EP2499239A1 (en) | 2009-11-11 | 2012-09-19 | Sanford-Burnham Medical Research Institute | METHOD FOR GENERATION AND REGULATION OF iPS CELLS AND COMPOSITIONS THEREOF |
US20130189741A1 (en) | 2009-12-07 | 2013-07-25 | Cellscript, Inc. | Compositions and methods for reprogramming mammalian cells |
US8808982B2 (en) | 2009-12-07 | 2014-08-19 | Cellscript, Llc | Compositions and methods for reprogramming eukaryotic cells |
AU2010327998B2 (en) | 2009-12-10 | 2015-11-12 | Iowa State University Research Foundation, Inc. | TAL effector-mediated DNA modification |
US8557972B2 (en) | 2009-12-21 | 2013-10-15 | University Of Washington Through Its Center For Commercialization | Compositions and methods for transfection of RNA and controlled stabilization of transfected RNA |
CA2788635A1 (en) | 2010-02-01 | 2011-08-04 | The Board Of Trustees Of The Leland Stanford Junior University | Enhanced efficiency of induced pluripotent stem cell generation |
US20140194482A1 (en) | 2010-02-02 | 2014-07-10 | Scioderm, Inc. | Compositions and methods of treatment of inflammatory skin conditions using allantoin |
WO2011110886A1 (en) | 2010-03-09 | 2011-09-15 | Biolamina Ab | Composition and method for enabling proliferation of pluripotent human stem cells |
EP3072961A1 (en) | 2010-04-16 | 2016-09-28 | Children's Medical Center Corporation | Sustained polypeptide expression from synthetic, modified rnas and uses thereof |
US9725695B2 (en) | 2010-05-05 | 2017-08-08 | The Regents Of The University Of California | Stem cell defined media for xeno-free and feeder free conditions and uses thereof |
US8048675B1 (en) | 2010-05-12 | 2011-11-01 | Ipierian, Inc. | Integration-free human induced pluripotent stem cells from blood |
EP2569424A1 (en) | 2010-05-12 | 2013-03-20 | Cellectis | Meganuclease variants cleaving a dna target sequence from the dystrophin gene and uses thereof |
JP6208580B2 (ja) | 2010-05-17 | 2017-10-04 | サンガモ セラピューティクス, インコーポレイテッド | 新規のdna結合タンパク質及びその使用 |
EP2392208B1 (en) | 2010-06-07 | 2016-05-04 | Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) | Fusion proteins comprising a DNA-binding domain of a Tal effector protein and a non-specific cleavage domain of a restriction nuclease and their use |
JP6043999B2 (ja) | 2010-08-05 | 2016-12-14 | ウィスコンシン アラムニ リサーチ ファンデーション | ヒト多能性細胞培養のための簡易基本培地 |
EP3578205A1 (en) | 2010-08-06 | 2019-12-11 | ModernaTX, Inc. | A pharmaceutical formulation comprising engineered nucleic acids and medical use thereof |
US9447408B2 (en) | 2010-09-14 | 2016-09-20 | Kyoto University | Method of efficiently establishing induced pluripotent stem cells |
WO2012045082A2 (en) | 2010-10-01 | 2012-04-05 | Jason Schrum | Engineered nucleic acids and methods of use thereof |
US20130273656A1 (en) | 2010-10-08 | 2013-10-17 | Regents Of The University Of Minnesota | Method to increase gene targeting frequency |
US9637732B2 (en) | 2010-11-04 | 2017-05-02 | Kyoto University | Method of efficiently establishing induced pluripotent stem cells |
CN103502436A (zh) | 2011-03-07 | 2014-01-08 | 麻省理工学院 | 用核酸转染细胞的方法 |
AU2012236099A1 (en) | 2011-03-31 | 2013-10-03 | Moderna Therapeutics, Inc. | Delivery and formulation of engineered nucleic acids |
WO2012131090A1 (en) * | 2011-03-31 | 2012-10-04 | Galderma Research & Development | Method for treatment of xeroderma pigmentosum |
JP2014511694A (ja) | 2011-04-03 | 2014-05-19 | ザ ジェネラル ホスピタル コーポレーション ドゥーイング ビジネス アズ マサチューセッツ ジェネラル ホスピタル | 修飾型rna(mod−rna)を使用する効率的なインビボタンパク質発現 |
WO2012174224A2 (en) * | 2011-06-17 | 2012-12-20 | Calando Pharmaceuticals, Inc. | Methods for administering nucleic acid-based therapeutics |
WO2012176015A1 (en) * | 2011-06-24 | 2012-12-27 | Leo Pharma A/S | Methods for treating uv-damaged skin and scc tumors and for removing tattoos with topical ingenol mebutate |
US9862926B2 (en) | 2011-06-27 | 2018-01-09 | Cellscript, Llc. | Inhibition of innate immune response |
US20130040302A1 (en) * | 2011-07-11 | 2013-02-14 | Thomas J. Burke | Methods for cell reprogramming and genome engineering |
CN108165593A (zh) | 2011-08-03 | 2018-06-15 | 凤凰组织修复公司 | 胶原蛋白7及相关方法 |
EP3682905B1 (en) | 2011-10-03 | 2021-12-01 | ModernaTX, Inc. | Modified nucleosides, nucleotides, and nucleic acids, and uses thereof |
US9340783B2 (en) * | 2011-10-11 | 2016-05-17 | Inserm (Institut National De La Sante Et De La Recherche Medicale | Exon skipping therapy for dystrophic epidermolysis bullosa |
US8497124B2 (en) | 2011-12-05 | 2013-07-30 | Factor Bioscience Inc. | Methods and products for reprogramming cells to a less differentiated state |
DK2791160T3 (da) | 2011-12-16 | 2022-05-30 | Modernatx Inc | Modificerede mrna-sammensætninger |
WO2013096709A2 (en) | 2011-12-21 | 2013-06-27 | modeRNA Therapeutics | Methods of increasing the viability or longevity of an organ or organ explant |
DK2798064T3 (en) | 2011-12-30 | 2016-12-19 | Cellscript Llc | PRODUCTION AND USE OF IN VITRO synthesized ssRNA TO FEED IN MAMMALIAN CELLS FOR INDUCTION OF A BIOLOGICAL OR BIOCHEMICAL EFFECT |
DE18200782T1 (de) * | 2012-04-02 | 2021-10-21 | Modernatx, Inc. | Modifizierte polynukleotide zur herstellung von proteinen im zusammenhang mit erkrankungen beim menschen |
SG10201809901SA (en) | 2012-04-24 | 2018-12-28 | Vcell Therapeutics Inc | Generating Pluripotent Cells De Novo |
ES2729563T3 (es) | 2012-05-13 | 2019-11-04 | Allele Biotechnology & Pharmaceuticals Inc | Derivación sin alimentadores de células madre pluripotentes inducidas humanas con ARN mensajero sintético |
US10155929B2 (en) | 2012-05-13 | 2018-12-18 | Allele Biotechnology & Pharmaceuticals, Inc. | Feeder-free derivation of human-induced pluripotent stem cells with synthetic messenger RNA |
US10119150B2 (en) | 2012-05-13 | 2018-11-06 | Allele Biotechnology & Pharmaceuticals, Inc. | Feeder-free Derivation of human-induced pluripotent stem cells with synthetic messenger RNA |
US20140031295A1 (en) | 2012-07-19 | 2014-01-30 | Lotus Tissue Repair, Inc. | Recombinant C7 and Methods of Use |
KR101979746B1 (ko) * | 2012-09-13 | 2019-05-17 | (주)아모레퍼시픽 | 전기 천공 장치 |
ES2658401T3 (es) * | 2012-12-12 | 2018-03-09 | The Broad Institute, Inc. | Suministro, modificación y optimización de sistemas, métodos y composiciones para la manipulación de secuencias y aplicaciones terapéuticas |
AU2014218667A1 (en) | 2013-02-22 | 2015-10-08 | The Board Of Trustees Of The Leland Stanford Junior University | Compounds, compositions, methods, and kits relating to telomere extension |
WO2014134412A1 (en) * | 2013-03-01 | 2014-09-04 | Regents Of The University Of Minnesota | Talen-based gene correction |
WO2015038075A1 (en) * | 2013-09-16 | 2015-03-19 | Agency For Science, Technology And Research | Method |
-
2015
- 2015-01-30 DK DK20161924.4T patent/DK3690056T5/da active
- 2015-01-30 ES ES15743915T patent/ES2787198T3/es active Active
- 2015-01-30 US US14/761,461 patent/US9770489B2/en active Active
- 2015-01-30 FI FIEP20161924.4T patent/FI3690056T3/fi active
- 2015-01-30 KR KR1020227022074A patent/KR20220100078A/ko active IP Right Grant
- 2015-01-30 BR BR112016017736A patent/BR112016017736A2/pt not_active Application Discontinuation
- 2015-01-30 KR KR1020167019564A patent/KR102415811B1/ko active IP Right Grant
- 2015-01-30 CA CA2937036A patent/CA2937036A1/en active Pending
- 2015-01-30 WO PCT/US2015/013949 patent/WO2015117021A1/en active Application Filing
- 2015-01-30 AU AU2015210769A patent/AU2015210769B2/en active Active
- 2015-01-30 RU RU2016131251A patent/RU2714404C2/ru active
- 2015-01-30 RU RU2020104969A patent/RU2020104969A/ru unknown
- 2015-01-30 JP JP2016533700A patent/JP2017510542A/ja active Pending
- 2015-01-30 EP EP22216417.0A patent/EP4249036A3/en active Pending
- 2015-01-30 CN CN201580006437.9A patent/CN105940110A/zh active Pending
- 2015-01-30 MX MX2016009771A patent/MX2016009771A/es active IP Right Grant
- 2015-01-30 EP EP20161924.4A patent/EP3690056B1/en active Active
- 2015-01-30 ES ES20161924T patent/ES2939542T3/es active Active
- 2015-01-30 EP EP15743915.9A patent/EP3099801B1/en active Active
-
2016
- 2016-07-27 MX MX2020006065A patent/MX2020006065A/es unknown
-
2017
- 2017-08-16 US US15/678,491 patent/US10124042B2/en active Active
-
2018
- 2018-06-12 US US16/006,461 patent/US20180271951A1/en not_active Abandoned
-
2019
- 2019-03-07 AU AU2019201576A patent/AU2019201576A1/en not_active Abandoned
- 2019-09-06 US US16/562,494 patent/US20200046807A1/en active Pending
-
2020
- 2020-07-30 JP JP2020128881A patent/JP7235702B2/ja active Active
-
2022
- 2022-02-17 AU AU2022201056A patent/AU2022201056A1/en active Pending
-
2023
- 2023-02-24 JP JP2023026873A patent/JP2023075165A/ja active Pending
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2013086008A1 (en) | 2011-12-05 | 2013-06-13 | Factor Bioscience Inc. | Methods and products for transfecting cells |
Non-Patent Citations (3)
Title |
---|
Chen M et al.,Restoration of type VII collagen expression and function in dystrophic epidermolysis bullosa,Nature Genetics,2002年,Vol.32, No.4,p.670-675 |
Murauer EM et al.,Functional correction of type VII collagen expression in dystrophic epidermolysis bullosa,Journal of Investigative Dermatology,2011年,Vol.131, No.1,p.74-83 |
Osborn MJ, et al.,TALEN-based gene correction for epidermolysis bullosa,Molecular Therapy,2013年04月02日,Vol.21, No.6,p.1151-1159 |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP7235702B2 (ja) | 核酸生成及び送達のための方法及び製品 | |
CN109803977B (zh) | 核酸产品及其施用方法 | |
JP7199809B2 (ja) | 核酸製品及びその投与方法 | |
WO2019191341A1 (en) | Nucleic acid-based therapeutics | |
KR102596302B1 (ko) | 세포에서 단백질을 발현시키는 방법들과 생성물들 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200827 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20200827 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200828 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20210803 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20211028 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20211227 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220203 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20220203 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20220704 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20221004 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20230125 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20230224 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 7235702 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |