JP2016539623A5 - - Google Patents

Info

Publication number

JP2016539623A5

JP2016539623A5 JP2016519974A JP2016519974A JP2016539623A5 JP 2016539623 A5 JP2016539623 A5 JP 2016539623A5 JP 2016519974 A JP2016519974 A JP 2016519974A JP 2016519974 A JP2016519974 A JP 2016519974A JP 2016539623 A5 JP2016539623 A5 JP 2016539623A5

Authority

JP

Japan

Prior art keywords

dsrna

antisense

sequence

sense

alas1

Prior art date

2014-10-03

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.)

Granted

Links

• Espacenet
• Global Dossier
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• 230000000692 anti-sense effect Effects 0.000 claims 55
• 238000000034 method Methods 0.000 claims 36
• 102100030755 5-aminolevulinate synthase, nonspecific, mitochondrial Human genes 0.000 claims 31
• 101000843649 Homo sapiens 5-aminolevulinate synthase, nonspecific, mitochondrial Proteins 0.000 claims 31
• 108091081021 Sense strand Proteins 0.000 claims 29
• 125000003729 nucleotide group Chemical group 0.000 claims 23
• 241000097929 Porphyria Species 0.000 claims 18
• 208000010642 Porphyrias Diseases 0.000 claims 18
• 239000000203 mixture Substances 0.000 claims 15
• 239000000523 sample Substances 0.000 claims 15
• 108020004999 messenger RNA Proteins 0.000 claims 13
• 239000002773 nucleotide Substances 0.000 claims 12
• ZGXJTSGNIOSYLO-UHFFFAOYSA-N 88755TAZ87 Chemical compound NCC(=O)CCC(O)=O ZGXJTSGNIOSYLO-UHFFFAOYSA-N 0.000 claims 11
• 239000003446 ligand Substances 0.000 claims 11
• QSHWIQZFGQKFMA-UHFFFAOYSA-N Porphobilinogen Natural products NCC=1NC=C(CCC(O)=O)C=1CC(O)=O QSHWIQZFGQKFMA-UHFFFAOYSA-N 0.000 claims 10
• YPHQRHBJEUDWJW-UHFFFAOYSA-N porphobilinogen Chemical compound NCC1=NC=C(CCC(O)=O)[C]1CC(O)=O YPHQRHBJEUDWJW-UHFFFAOYSA-N 0.000 claims 10
• 229920002477 rna polymer Polymers 0.000 claims 10
• 108091032973 (ribonucleotides)n+m Proteins 0.000 claims 7
• 230000001154 acute effect Effects 0.000 claims 7
• 230000002401 inhibitory effect Effects 0.000 claims 7
• 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 claims 6
• 210000004027 cell Anatomy 0.000 claims 6
• 230000000295 complement effect Effects 0.000 claims 6
• 239000002342 ribonucleoside Substances 0.000 claims 6
• 239000013060 biological fluid Substances 0.000 claims 5
• 239000002299 complementary DNA Substances 0.000 claims 5
• RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims 5
• 210000003494 hepatocyte Anatomy 0.000 claims 4
• 238000012986 modification Methods 0.000 claims 4
• 230000004048 modification Effects 0.000 claims 4
• OOOQNKMJLOLMHC-UHFFFAOYSA-N 5-[[3,4-diethyl-5-[[5-formyl-3-(3-hydroxypropyl)-4-methyl-1h-pyrrol-2-yl]methyl]-1h-pyrrol-2-yl]methyl]-4-(3-hydroxypropyl)-3-methyl-1h-pyrrole-2-carbaldehyde Chemical compound N1C(CC2=C(C(C)=C(C=O)N2)CCCO)=C(CC)C(CC)=C1CC=1NC(C=O)=C(C)C=1CCCO OOOQNKMJLOLMHC-UHFFFAOYSA-N 0.000 claims 3
• 101150038201 ALAS1 gene Proteins 0.000 claims 3
• OVRNDRQMDRJTHS-KEWYIRBNSA-N N-acetyl-D-galactosamine Chemical compound CC(=O)N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-KEWYIRBNSA-N 0.000 claims 3
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 3
• 108020004707 nucleic acids Proteins 0.000 claims 3
• 102000039446 nucleic acids Human genes 0.000 claims 3
• 150000007523 nucleic acids Chemical class 0.000 claims 3
• 239000008194 pharmaceutical composition Substances 0.000 claims 3
• 150000004032 porphyrins Chemical class 0.000 claims 3
• 208000024891 symptom Diseases 0.000 claims 3
• 210000002700 urine Anatomy 0.000 claims 3
• 102000040650 (ribonucleotides)n+m Human genes 0.000 claims 2
• 206010010904 Convulsion Diseases 0.000 claims 2
• MBLBDJOUHNCFQT-UHFFFAOYSA-N N-acetyl-D-galactosamine Natural products CC(=O)NC(C=O)C(O)C(O)C(O)CO MBLBDJOUHNCFQT-UHFFFAOYSA-N 0.000 claims 2
• 208000002193 Pain Diseases 0.000 claims 2
• 210000004369 blood Anatomy 0.000 claims 2
• 239000008280 blood Substances 0.000 claims 2
• 239000011541 reaction mixture Substances 0.000 claims 2
• 210000002966 serum Anatomy 0.000 claims 2
• 230000003442 weekly effect Effects 0.000 claims 2
• BMUDPLZKKRQECS-UHFFFAOYSA-K 3-[18-(2-carboxyethyl)-8,13-bis(ethenyl)-3,7,12,17-tetramethylporphyrin-21,24-diid-2-yl]propanoic acid iron(3+) hydroxide Chemical compound [OH-].[Fe+3].[N-]1C2=C(C)C(CCC(O)=O)=C1C=C([N-]1)C(CCC(O)=O)=C(C)C1=CC(C(C)=C1C=C)=NC1=CC(C(C)=C1C=C)=NC1=C2 BMUDPLZKKRQECS-UHFFFAOYSA-K 0.000 claims 1
• 208000005452 Acute intermittent porphyria Diseases 0.000 claims 1
• 208000000094 Chronic Pain Diseases 0.000 claims 1
• 108091007413 Extracellular RNA Proteins 0.000 claims 1
• 102000004867 Hydro-Lyases Human genes 0.000 claims 1
• 108090001042 Hydro-Lyases Proteins 0.000 claims 1
• OVRNDRQMDRJTHS-CBQIKETKSA-N N-Acetyl-D-Galactosamine Chemical compound CC(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-CBQIKETKSA-N 0.000 claims 1
• 208000028389 Nerve injury Diseases 0.000 claims 1
• 206010036182 Porphyria acute Diseases 0.000 claims 1
• 208000037048 Prodromal Symptoms Diseases 0.000 claims 1
• 238000011529 RT qPCR Methods 0.000 claims 1
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims 1
• 108020004566 Transfer RNA Proteins 0.000 claims 1
• 239000007864 aqueous solution Substances 0.000 claims 1
• 150000001720 carbohydrates Chemical class 0.000 claims 1
• 230000015556 catabolic process Effects 0.000 claims 1
• 230000002950 deficient Effects 0.000 claims 1
• 238000006731 degradation reaction Methods 0.000 claims 1
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
• 208000035475 disorder Diseases 0.000 claims 1
• 230000000694 effects Effects 0.000 claims 1
• 230000005713 exacerbation Effects 0.000 claims 1
• 210000001808 exosome Anatomy 0.000 claims 1
• 229940109738 hematin Drugs 0.000 claims 1
• 230000003834 intracellular effect Effects 0.000 claims 1
• 230000005906 menstruation Effects 0.000 claims 1
• 230000008764 nerve damage Effects 0.000 claims 1
• 201000001119 neuropathy Diseases 0.000 claims 1
• 230000007823 neuropathy Effects 0.000 claims 1
• 208000033808 peripheral neuropathy Diseases 0.000 claims 1
• 230000000306 recurrent effect Effects 0.000 claims 1
• 239000011780 sodium chloride Substances 0.000 claims 1
• 238000007920 subcutaneous administration Methods 0.000 claims 1
• 238000010254 subcutaneous injection Methods 0.000 claims 1
• 239000007929 subcutaneous injection Substances 0.000 claims 1
• 210000001519 tissue Anatomy 0.000 claims 1
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 1
• 239000008215 water for injection Substances 0.000 claims 1
• 0 CC1*(*)C(*)C(C2CC(CCCCC(C)=O)C2)[Tl]C1C[U] Chemical compound CC1*(*)C(*)C(C2CC(CCCCC(C)=O)C2)[Tl]C1C[U] 0.000 description 4