DK2270162T3 - PRESERVED HBV AND HCV SEQUENCES USED FOR GEN-SILENCING - Google Patents
PRESERVED HBV AND HCV SEQUENCES USED FOR GEN-SILENCING Download PDFInfo
- Publication number
- DK2270162T3 DK2270162T3 DK10180048.0T DK10180048T DK2270162T3 DK 2270162 T3 DK2270162 T3 DK 2270162T3 DK 10180048 T DK10180048 T DK 10180048T DK 2270162 T3 DK2270162 T3 DK 2270162T3
- Authority
- DK
- Denmark
- Prior art keywords
- seq
- sequences
- hbv
- rna
- promoter
- Prior art date
Links
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 214
- 102000040650 (ribonucleotides)n+m Human genes 0.000 claims description 214
- 210000004027 cell Anatomy 0.000 claims description 160
- 230000014509 gene expression Effects 0.000 claims description 104
- 239000000203 mixture Substances 0.000 claims description 99
- 125000003729 nucleotide group Chemical group 0.000 claims description 77
- 239000002773 nucleotide Substances 0.000 claims description 76
- 238000000034 method Methods 0.000 claims description 59
- 239000012636 effector Substances 0.000 claims description 47
- 102000040430 polynucleotide Human genes 0.000 claims description 41
- 108091033319 polynucleotide Proteins 0.000 claims description 41
- 239000002157 polynucleotide Substances 0.000 claims description 41
- 239000013604 expression vector Substances 0.000 claims description 29
- 210000004962 mammalian cell Anatomy 0.000 claims description 28
- 241000700721 Hepatitis B virus Species 0.000 claims description 27
- 238000001727 in vivo Methods 0.000 claims description 22
- 230000002401 inhibitory effect Effects 0.000 claims description 16
- 238000000338 in vitro Methods 0.000 claims description 14
- 210000005260 human cell Anatomy 0.000 claims description 12
- 108010009460 RNA Polymerase II Proteins 0.000 claims description 11
- 102000009572 RNA Polymerase II Human genes 0.000 claims description 11
- 108010078067 RNA Polymerase III Proteins 0.000 claims description 8
- 102000014450 RNA Polymerase III Human genes 0.000 claims description 8
- 230000002438 mitochondrial effect Effects 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 108010013845 RNA Polymerase I Proteins 0.000 claims description 4
- 102000017143 RNA Polymerase I Human genes 0.000 claims description 4
- 230000003213 activating effect Effects 0.000 claims 2
- 108020004414 DNA Proteins 0.000 description 163
- 102000053602 DNA Human genes 0.000 description 162
- 229920002477 rna polymer Polymers 0.000 description 151
- 239000013598 vector Substances 0.000 description 111
- 238000001890 transfection Methods 0.000 description 80
- 108090000623 proteins and genes Proteins 0.000 description 77
- 239000013612 plasmid Substances 0.000 description 71
- 150000007523 nucleic acids Chemical class 0.000 description 68
- 102000039446 nucleic acids Human genes 0.000 description 63
- 108020004707 nucleic acids Proteins 0.000 description 63
- 238000002474 experimental method Methods 0.000 description 58
- 230000010076 replication Effects 0.000 description 56
- 108020004459 Small interfering RNA Proteins 0.000 description 55
- 230000003612 virological effect Effects 0.000 description 52
- 238000013507 mapping Methods 0.000 description 44
- 239000004055 small Interfering RNA Substances 0.000 description 44
- 208000015181 infectious disease Diseases 0.000 description 42
- 241000282414 Homo sapiens Species 0.000 description 39
- 241000700605 Viruses Species 0.000 description 34
- 241001465754 Metazoa Species 0.000 description 33
- 230000002458 infectious effect Effects 0.000 description 33
- 108020004999 messenger RNA Proteins 0.000 description 33
- 102000004169 proteins and genes Human genes 0.000 description 32
- 241000711549 Hepacivirus C Species 0.000 description 28
- 210000003494 hepatocyte Anatomy 0.000 description 27
- 101710137500 T7 RNA polymerase Proteins 0.000 description 25
- 230000000692 anti-sense effect Effects 0.000 description 23
- 239000003795 chemical substances by application Substances 0.000 description 23
- 239000002245 particle Substances 0.000 description 23
- 238000013518 transcription Methods 0.000 description 23
- 230000035897 transcription Effects 0.000 description 23
- 238000009472 formulation Methods 0.000 description 22
- 230000009368 gene silencing by RNA Effects 0.000 description 20
- 241000699670 Mus sp. Species 0.000 description 19
- 108091007433 antigens Proteins 0.000 description 19
- 230000030279 gene silencing Effects 0.000 description 19
- 230000005764 inhibitory process Effects 0.000 description 19
- 210000004185 liver Anatomy 0.000 description 19
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 18
- 210000002845 virion Anatomy 0.000 description 18
- 102000036639 antigens Human genes 0.000 description 17
- 238000004113 cell culture Methods 0.000 description 17
- 230000028327 secretion Effects 0.000 description 17
- 239000000427 antigen Substances 0.000 description 16
- 230000015572 biosynthetic process Effects 0.000 description 16
- 208000002672 hepatitis B Diseases 0.000 description 16
- 230000029812 viral genome replication Effects 0.000 description 16
- 108091027967 Small hairpin RNA Proteins 0.000 description 15
- 238000004458 analytical method Methods 0.000 description 15
- 230000000295 complement effect Effects 0.000 description 15
- PFNFFQXMRSDOHW-UHFFFAOYSA-N spermine Chemical compound NCCCNCCCCNCCCN PFNFFQXMRSDOHW-UHFFFAOYSA-N 0.000 description 15
- 239000013613 expression plasmid Substances 0.000 description 14
- 230000001404 mediated effect Effects 0.000 description 14
- 239000002299 complementary DNA Substances 0.000 description 13
- 230000008685 targeting Effects 0.000 description 13
- 230000001225 therapeutic effect Effects 0.000 description 13
- 108091028043 Nucleic acid sequence Proteins 0.000 description 12
- 239000003814 drug Substances 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 238000003786 synthesis reaction Methods 0.000 description 12
- 238000000636 Northern blotting Methods 0.000 description 11
- 230000007423 decrease Effects 0.000 description 11
- 238000011282 treatment Methods 0.000 description 11
- 101000600434 Homo sapiens Putative uncharacterized protein encoded by MIR7-3HG Proteins 0.000 description 10
- 108091034117 Oligonucleotide Proteins 0.000 description 10
- 102100037401 Putative uncharacterized protein encoded by MIR7-3HG Human genes 0.000 description 10
- 208000006454 hepatitis Diseases 0.000 description 10
- 231100000283 hepatitis Toxicity 0.000 description 10
- 238000010172 mouse model Methods 0.000 description 10
- 244000052769 pathogen Species 0.000 description 10
- 229940063675 spermine Drugs 0.000 description 10
- 239000007771 core particle Substances 0.000 description 9
- 229940124447 delivery agent Drugs 0.000 description 9
- 239000013641 positive control Substances 0.000 description 9
- 238000002560 therapeutic procedure Methods 0.000 description 9
- 108700026244 Open Reading Frames Proteins 0.000 description 8
- 108091028664 Ribonucleotide Proteins 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 238000012226 gene silencing method Methods 0.000 description 8
- -1 hybrid Proteins 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 239000002336 ribonucleotide Substances 0.000 description 8
- 125000002652 ribonucleotide group Chemical group 0.000 description 8
- 101100297347 Caenorhabditis elegans pgl-3 gene Proteins 0.000 description 7
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 7
- 208000005176 Hepatitis C Diseases 0.000 description 7
- 239000012124 Opti-MEM Substances 0.000 description 7
- 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 7
- 238000013459 approach Methods 0.000 description 7
- 230000003247 decreasing effect Effects 0.000 description 7
- 230000003828 downregulation Effects 0.000 description 7
- 230000001717 pathogenic effect Effects 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 241001515965 unidentified phage Species 0.000 description 7
- 239000013603 viral vector Substances 0.000 description 7
- 108091026890 Coding region Proteins 0.000 description 6
- 229920000858 Cyclodextrin Polymers 0.000 description 6
- 108010067770 Endopeptidase K Proteins 0.000 description 6
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 238000007796 conventional method Methods 0.000 description 6
- 238000011161 development Methods 0.000 description 6
- 210000005229 liver cell Anatomy 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 231100000419 toxicity Toxicity 0.000 description 6
- 230000001988 toxicity Effects 0.000 description 6
- 238000011830 transgenic mouse model Methods 0.000 description 6
- 238000001262 western blot Methods 0.000 description 6
- 108020005345 3' Untranslated Regions Proteins 0.000 description 5
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 108020000999 Viral RNA Proteins 0.000 description 5
- 238000010171 animal model Methods 0.000 description 5
- 230000003466 anti-cipated effect Effects 0.000 description 5
- 108091036078 conserved sequence Proteins 0.000 description 5
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 5
- 238000013461 design Methods 0.000 description 5
- 238000011156 evaluation Methods 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 239000003446 ligand Substances 0.000 description 5
- 208000019423 liver disease Diseases 0.000 description 5
- 238000010369 molecular cloning Methods 0.000 description 5
- 230000030648 nucleus localization Effects 0.000 description 5
- 238000004806 packaging method and process Methods 0.000 description 5
- 230000001105 regulatory effect Effects 0.000 description 5
- 238000010839 reverse transcription Methods 0.000 description 5
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- 230000002459 sustained effect Effects 0.000 description 5
- 230000009466 transformation Effects 0.000 description 5
- 238000013519 translation Methods 0.000 description 5
- 102000005427 Asialoglycoprotein Receptor Human genes 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 4
- 101710132601 Capsid protein Proteins 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 102000016911 Deoxyribonucleases Human genes 0.000 description 4
- 108010053770 Deoxyribonucleases Proteins 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- 102000000574 RNA-Induced Silencing Complex Human genes 0.000 description 4
- 108010016790 RNA-Induced Silencing Complex Proteins 0.000 description 4
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 101710086987 X protein Proteins 0.000 description 4
- 108010006523 asialoglycoprotein receptor Proteins 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 230000001580 bacterial effect Effects 0.000 description 4
- 150000001720 carbohydrates Chemical class 0.000 description 4
- 235000014633 carbohydrates Nutrition 0.000 description 4
- 125000002091 cationic group Chemical group 0.000 description 4
- 239000003184 complementary RNA Substances 0.000 description 4
- 239000005547 deoxyribonucleotide Substances 0.000 description 4
- 239000000945 filler Substances 0.000 description 4
- 230000002068 genetic effect Effects 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 4
- 230000001939 inductive effect Effects 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- 230000036961 partial effect Effects 0.000 description 4
- 230000000069 prophylactic effect Effects 0.000 description 4
- 230000003362 replicative effect Effects 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 238000010561 standard procedure Methods 0.000 description 4
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 4
- 241000701161 unidentified adenovirus Species 0.000 description 4
- 241001430294 unidentified retrovirus Species 0.000 description 4
- 102100027211 Albumin Human genes 0.000 description 3
- 108010088751 Albumins Proteins 0.000 description 3
- 108020005544 Antisense RNA Proteins 0.000 description 3
- 101000909256 Caldicellulosiruptor bescii (strain ATCC BAA-1888 / DSM 6725 / Z-1320) DNA polymerase I Proteins 0.000 description 3
- 208000000419 Chronic Hepatitis B Diseases 0.000 description 3
- 241000701832 Enterobacteria phage T3 Species 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 108700039791 Hepatitis C virus nucleocapsid Proteins 0.000 description 3
- 102000014150 Interferons Human genes 0.000 description 3
- 108010050904 Interferons Proteins 0.000 description 3
- 108010047294 Lamins Proteins 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 241000283923 Marmota monax Species 0.000 description 3
- 108060004795 Methyltransferase Proteins 0.000 description 3
- 101800001014 Non-structural protein 5A Proteins 0.000 description 3
- 108091093037 Peptide nucleic acid Proteins 0.000 description 3
- 208000037581 Persistent Infection Diseases 0.000 description 3
- 101000902592 Pyrococcus furiosus (strain ATCC 43587 / DSM 3638 / JCM 8422 / Vc1) DNA polymerase Proteins 0.000 description 3
- 108091027544 Subgenomic mRNA Proteins 0.000 description 3
- 108020004566 Transfer RNA Proteins 0.000 description 3
- 101150003160 X gene Proteins 0.000 description 3
- 239000003443 antiviral agent Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 230000019113 chromatin silencing Effects 0.000 description 3
- 230000001086 cytosolic effect Effects 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 108700008776 hepatitis C virus NS-5 Proteins 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 229940079322 interferon Drugs 0.000 description 3
- 229960001627 lamivudine Drugs 0.000 description 3
- JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 108091064355 mitochondrial RNA Proteins 0.000 description 3
- 238000012544 monitoring process Methods 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 229920001184 polypeptide Polymers 0.000 description 3
- 230000032361 posttranscriptional gene silencing Effects 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 238000003757 reverse transcription PCR Methods 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000010189 synthetic method Methods 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 230000002103 transcriptional effect Effects 0.000 description 3
- 238000012033 transcriptional gene silencing Methods 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 241001529453 unidentified herpesvirus Species 0.000 description 3
- 229960005486 vaccine Drugs 0.000 description 3
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- 206010059193 Acute hepatitis B Diseases 0.000 description 2
- 241000710929 Alphavirus Species 0.000 description 2
- 241000272525 Anas platyrhynchos Species 0.000 description 2
- 108090000994 Catalytic RNA Proteins 0.000 description 2
- 102000053642 Catalytic RNA Human genes 0.000 description 2
- 108020004638 Circular DNA Proteins 0.000 description 2
- 108091028075 Circular RNA Proteins 0.000 description 2
- 241000701022 Cytomegalovirus Species 0.000 description 2
- 101710177611 DNA polymerase II large subunit Proteins 0.000 description 2
- 101710184669 DNA polymerase II small subunit Proteins 0.000 description 2
- 241000702421 Dependoparvovirus Species 0.000 description 2
- 241000725618 Duck hepatitis B virus Species 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- XQSPYNMVSIKCOC-NTSWFWBYSA-N Emtricitabine Chemical compound C1=C(F)C(N)=NC(=O)N1[C@H]1O[C@@H](CO)SC1 XQSPYNMVSIKCOC-NTSWFWBYSA-N 0.000 description 2
- 101000686777 Escherichia phage T7 T7 RNA polymerase Proteins 0.000 description 2
- 206010016654 Fibrosis Diseases 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 108091060210 Heavy strand Proteins 0.000 description 2
- 102100034349 Integrase Human genes 0.000 description 2
- 102000006835 Lamins Human genes 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- 108700019961 Neoplasm Genes Proteins 0.000 description 2
- 102000048850 Neoplasm Genes Human genes 0.000 description 2
- 241000282579 Pan Species 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 108010065868 RNA polymerase SP6 Proteins 0.000 description 2
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 description 2
- 108091081021 Sense strand Proteins 0.000 description 2
- 241000700584 Simplexvirus Species 0.000 description 2
- 238000002105 Southern blotting Methods 0.000 description 2
- 108091023040 Transcription factor Proteins 0.000 description 2
- 102000040945 Transcription factor Human genes 0.000 description 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 208000037628 acute hepatitis B virus infection Diseases 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 102000015395 alpha 1-Antitrypsin Human genes 0.000 description 2
- 108010050122 alpha 1-Antitrypsin Proteins 0.000 description 2
- 229940024142 alpha 1-antitrypsin Drugs 0.000 description 2
- 108010026331 alpha-Fetoproteins Proteins 0.000 description 2
- 102000013529 alpha-Fetoproteins Human genes 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- 210000004507 artificial chromosome Anatomy 0.000 description 2
- 230000002238 attenuated effect Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 238000001815 biotherapy Methods 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000002759 chromosomal effect Effects 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 210000004748 cultured cell Anatomy 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 241001493065 dsRNA viruses Species 0.000 description 2
- 238000004520 electroporation Methods 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000001502 gel electrophoresis Methods 0.000 description 2
- 238000001476 gene delivery Methods 0.000 description 2
- 238000001415 gene therapy Methods 0.000 description 2
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 2
- 230000002440 hepatic effect Effects 0.000 description 2
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 2
- 210000003917 human chromosome Anatomy 0.000 description 2
- 238000009396 hybridization Methods 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 208000037850 immune anergy Diseases 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 210000005053 lamin Anatomy 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 239000003589 local anesthetic agent Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 238000000520 microinjection Methods 0.000 description 2
- 238000010899 nucleation Methods 0.000 description 2
- 210000004940 nucleus Anatomy 0.000 description 2
- 239000013600 plasmid vector Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 229960000329 ribavirin Drugs 0.000 description 2
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 description 2
- 108020004418 ribosomal RNA Proteins 0.000 description 2
- 108091092562 ribozyme Proteins 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 230000009221 stress response pathway Effects 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 238000007910 systemic administration Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 229940113082 thymine Drugs 0.000 description 2
- 230000009261 transgenic effect Effects 0.000 description 2
- ZDSRFXVZVHSYMA-CMOCDZPBSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-carboxybutanoyl]amino]pentanedioic acid Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O)C1=CC=C(O)C=C1 ZDSRFXVZVHSYMA-CMOCDZPBSA-N 0.000 description 1
- LEBVLXFERQHONN-UHFFFAOYSA-N 1-butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide Chemical compound CCCCN1CCCCC1C(=O)NC1=C(C)C=CC=C1C LEBVLXFERQHONN-UHFFFAOYSA-N 0.000 description 1
- AXAVXPMQTGXXJZ-UHFFFAOYSA-N 2-aminoacetic acid;2-amino-2-(hydroxymethyl)propane-1,3-diol Chemical compound NCC(O)=O.OCC(N)(CO)CO AXAVXPMQTGXXJZ-UHFFFAOYSA-N 0.000 description 1
- YREOLPGEVLLKMB-UHFFFAOYSA-N 3-methylpyridin-1-ium-2-amine bromide hydrate Chemical compound O.[Br-].Cc1ccc[nH+]c1N YREOLPGEVLLKMB-UHFFFAOYSA-N 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 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
- BHELIUBJHYAEDK-OAIUPTLZSA-N Aspoxicillin Chemical compound C1([C@H](C(=O)N[C@@H]2C(N3[C@H](C(C)(C)S[C@@H]32)C(O)=O)=O)NC(=O)[C@H](N)CC(=O)NC)=CC=C(O)C=C1 BHELIUBJHYAEDK-OAIUPTLZSA-N 0.000 description 1
- 241000972773 Aulopiformes Species 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 208000006154 Chronic hepatitis C Diseases 0.000 description 1
- 208000003322 Coinfection Diseases 0.000 description 1
- 108020004394 Complementary RNA Proteins 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 229940086198 Corticosteroid antagonist Drugs 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 241001533413 Deltavirus Species 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- UPEZCKBFRMILAV-JNEQICEOSA-N Ecdysone Natural products O=C1[C@H]2[C@@](C)([C@@H]3C([C@@]4(O)[C@@](C)([C@H]([C@H]([C@@H](O)CCC(O)(C)C)C)CC4)CC3)=C1)C[C@H](O)[C@H](O)C2 UPEZCKBFRMILAV-JNEQICEOSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000991587 Enterovirus C Species 0.000 description 1
- 101710091045 Envelope protein Proteins 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241000710781 Flaviviridae Species 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 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 1
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 241000711557 Hepacivirus Species 0.000 description 1
- 108091027305 Heteroduplex Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 108700020121 Human Immunodeficiency Virus-1 rev Proteins 0.000 description 1
- 241000701024 Human betaherpesvirus 5 Species 0.000 description 1
- 101100195053 Human herpesvirus 1 (strain 17) RIR1 gene Proteins 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 101150017040 I gene Proteins 0.000 description 1
- 101150027427 ICP4 gene Proteins 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 108010047761 Interferon-alpha Proteins 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
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
- 241000713666 Lentivirus Species 0.000 description 1
- 206010067125 Liver injury Diseases 0.000 description 1
- 241000701076 Macacine alphaherpesvirus 1 Species 0.000 description 1
- 241000710118 Maize chlorotic mottle virus Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 1
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 108090001074 Nucleocapsid Proteins Proteins 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 108010076039 Polyproteins Proteins 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 101710188315 Protein X Proteins 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 241000283919 Psilotreta rossi Species 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 101800001554 RNA-directed RNA polymerase Proteins 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 108091081062 Repeated sequence (DNA) Proteins 0.000 description 1
- 241000220317 Rosa Species 0.000 description 1
- 241000714474 Rous sarcoma virus Species 0.000 description 1
- 239000012722 SDS sample buffer Substances 0.000 description 1
- 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- 101710172711 Structural protein Proteins 0.000 description 1
- 241000701093 Suid alphaherpesvirus 1 Species 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 108091036066 Three prime untranslated region Proteins 0.000 description 1
- 102000006601 Thymidine Kinase Human genes 0.000 description 1
- 108020004440 Thymidine kinase Proteins 0.000 description 1
- 241000838698 Togo Species 0.000 description 1
- 108091023045 Untranslated Region Proteins 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- 206010046865 Vaccinia virus infection Diseases 0.000 description 1
- 206010047139 Vasoconstriction Diseases 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 108020005202 Viral DNA Proteins 0.000 description 1
- 208000036141 Viral hepatitis carrier Diseases 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 241000726445 Viroids Species 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- WOZSCQDILHKSGG-UHFFFAOYSA-N adefovir depivoxil Chemical compound N1=CN=C2N(CCOCP(=O)(OCOC(=O)C(C)(C)C)OCOC(=O)C(C)(C)C)C=NC2=C1N WOZSCQDILHKSGG-UHFFFAOYSA-N 0.000 description 1
- 229960003205 adefovir dipivoxil Drugs 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- UPEZCKBFRMILAV-UHFFFAOYSA-N alpha-Ecdysone Natural products C1C(O)C(O)CC2(C)C(CCC3(C(C(C(O)CCC(C)(C)O)C)CCC33O)C)C3=CC(=O)C21 UPEZCKBFRMILAV-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 108010084541 asialoorosomucoid Proteins 0.000 description 1
- 108010028263 bacteriophage T3 RNA polymerase Proteins 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- WGQKYBSKWIADBV-UHFFFAOYSA-O benzylaminium Chemical compound [NH3+]CC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-O 0.000 description 1
- 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 1
- 230000008827 biological function Effects 0.000 description 1
- 229960003150 bupivacaine Drugs 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 239000013553 cell monolayer Substances 0.000 description 1
- 108091092356 cellular DNA Proteins 0.000 description 1
- 108091092328 cellular RNA Proteins 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 239000010415 colloidal nanoparticle Substances 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 239000003836 corticosteroid antagonist Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- DMSZORWOGDLWGN-UHFFFAOYSA-N ctk1a3526 Chemical compound NP(N)(N)=O DMSZORWOGDLWGN-UHFFFAOYSA-N 0.000 description 1
- 229940097362 cyclodextrins Drugs 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- SNTINBZZQZEOPH-OPOFJALESA-N dT5 Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(=O)O[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)O[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)O[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)O[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)CO)[C@@H](O)C1 SNTINBZZQZEOPH-OPOFJALESA-N 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000002716 delivery method Methods 0.000 description 1
- 239000000412 dendrimer Substances 0.000 description 1
- 229920000736 dendritic polymer Polymers 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- NAGJZTKCGNOGPW-UHFFFAOYSA-K dioxido-sulfanylidene-sulfido-$l^{5}-phosphane Chemical compound [O-]P([O-])([S-])=S NAGJZTKCGNOGPW-UHFFFAOYSA-K 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000002222 downregulating effect Effects 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- UPEZCKBFRMILAV-JMZLNJERSA-N ecdysone Chemical compound C1[C@@H](O)[C@@H](O)C[C@]2(C)[C@@H](CC[C@@]3([C@@H]([C@@H]([C@H](O)CCC(C)(C)O)C)CC[C@]33O)C)C3=CC(=O)[C@@H]21 UPEZCKBFRMILAV-JMZLNJERSA-N 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 229960000366 emtricitabine Drugs 0.000 description 1
- 229960000980 entecavir Drugs 0.000 description 1
- YXPVEXCTPGULBZ-WQYNNSOESA-N entecavir hydrate Chemical compound O.C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)C1=C YXPVEXCTPGULBZ-WQYNNSOESA-N 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 235000013861 fat-free Nutrition 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000003197 gene knockdown Methods 0.000 description 1
- 230000007614 genetic variation Effects 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 231100000234 hepatic damage Toxicity 0.000 description 1
- 208000010710 hepatitis C virus infection Diseases 0.000 description 1
- SPSXSWRZQFPVTJ-ZQQKUFEYSA-N hepatitis b vaccine Chemical compound C([C@H](NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CCSC)C(=O)N[C@@H](CC1N=CN=C1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)OC(=O)CNC(=O)CNC(=O)[C@H](C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@@H](N)CCCNC(N)=N)C1=CC=CC=C1 SPSXSWRZQFPVTJ-ZQQKUFEYSA-N 0.000 description 1
- 229940124736 hepatitis-B vaccine Drugs 0.000 description 1
- 230000004730 hepatocarcinogenesis Effects 0.000 description 1
- 150000002402 hexoses Chemical class 0.000 description 1
- 230000006801 homologous recombination Effects 0.000 description 1
- 238000002744 homologous recombination Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 229940124452 immunizing agent Drugs 0.000 description 1
- 230000006057 immunotolerant effect Effects 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000001638 lipofection Methods 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 230000008818 liver damage Effects 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 210000005228 liver tissue Anatomy 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 229940042443 other antivirals in atc Drugs 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 150000002972 pentoses Chemical class 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 229940021222 peritoneal dialysis isotonic solution Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000004713 phosphodiesters Chemical class 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920002851 polycationic polymer Polymers 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000004853 protein function Effects 0.000 description 1
- 230000020978 protein processing Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 239000002510 pyrogen Substances 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000000754 repressing effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000003938 response to stress Effects 0.000 description 1
- 102000029752 retinol binding Human genes 0.000 description 1
- 108010066034 retinol binding protein receptor Proteins 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 235000019515 salmon Nutrition 0.000 description 1
- 238000009738 saturating Methods 0.000 description 1
- 230000037390 scarring Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000003584 silencer Effects 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 108010068794 tyrosyl-tyrosyl-glutamyl-glutamic acid Proteins 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 208000007089 vaccinia Diseases 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—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
- C12N15/1131—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 against viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
-
- 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
-
- 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
- A61P31/14—Antivirals for RNA viruses
-
- 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
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/11—Antisense
- C12N2310/111—Antisense spanning the whole gene, or a large part of it
-
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]
-
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/50—Physical structure
- C12N2310/53—Physical structure partially self-complementary or closed
-
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/50—Physical structure
- C12N2310/53—Physical structure partially self-complementary or closed
- C12N2310/531—Stem-loop; Hairpin
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Virology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Plant Pathology (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US47807603P | 2003-06-12 | 2003-06-12 | |
| EP04776661A EP1631670B1 (en) | 2003-06-12 | 2004-06-10 | Conserved hbv and hcv sequences useful for gene silencing |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK2270162T3 true DK2270162T3 (en) | 2019-01-21 |
Family
ID=34135047
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK10180048.0T DK2270162T3 (en) | 2003-06-12 | 2004-06-10 | PRESERVED HBV AND HCV SEQUENCES USED FOR GEN-SILENCING |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US8350021B2 (cg-RX-API-DMAC7.html) |
| EP (4) | EP3470518A1 (cg-RX-API-DMAC7.html) |
| JP (2) | JP4980716B2 (cg-RX-API-DMAC7.html) |
| CN (1) | CN1836042A (cg-RX-API-DMAC7.html) |
| AU (1) | AU2004263832B2 (cg-RX-API-DMAC7.html) |
| BR (1) | BRPI0411219A (cg-RX-API-DMAC7.html) |
| CA (2) | CA3040025C (cg-RX-API-DMAC7.html) |
| DK (1) | DK2270162T3 (cg-RX-API-DMAC7.html) |
| HU (1) | HUE042261T2 (cg-RX-API-DMAC7.html) |
| IL (1) | IL172268A0 (cg-RX-API-DMAC7.html) |
| SG (1) | SG173218A1 (cg-RX-API-DMAC7.html) |
| SI (1) | SI2270162T1 (cg-RX-API-DMAC7.html) |
| WO (1) | WO2005014806A2 (cg-RX-API-DMAC7.html) |
Families Citing this family (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SG173218A1 (en) | 2003-06-12 | 2011-08-29 | Alnylam Pharmaceuticals Inc | Conserved hbv and hcv sequences useful for gene silencing |
| US8575327B2 (en) | 2003-06-12 | 2013-11-05 | Alnylam Pharmaceuticals, Inc. | Conserved HBV and HCV sequences useful for gene silencing |
| US20070265220A1 (en) | 2004-03-15 | 2007-11-15 | City Of Hope | Methods and compositions for the specific inhibition of gene expression by double-stranded RNA |
| US20050277610A1 (en) | 2004-03-15 | 2005-12-15 | City Of Hope | Methods and compositions for the specific inhibition of gene expression by double-stranded RNA |
| CA2577519A1 (en) | 2004-08-23 | 2006-03-30 | Nucleonics, Inc. | Multiple rna polymerase iii promoter expression constructs |
| EP1797185B1 (en) | 2004-09-24 | 2011-04-13 | Alnylam Pharmaceuticals, Inc. | Targeting opposite strand replication intermediates of single-stranded viruses by rnai |
| ATE507293T1 (de) * | 2004-12-22 | 2011-05-15 | Alnylam Pharmaceuticals Inc | Zum gen-silencing geeignete konservierte hbv- und hcv-sequenzen |
| WO2011103394A2 (en) * | 2010-02-19 | 2011-08-25 | Agave Pharma Inc. | Methods for gene inhibition |
| CA2791974A1 (en) * | 2010-03-01 | 2011-09-09 | The Children's Hospital Of Philadelphia | Nucleic acids for targeting multiple regions of the hcv genome |
| SI2606134T1 (sl) | 2010-08-17 | 2019-08-30 | Sirna Therapeutics, Inc. | RNA-INTERFERENČNO POSREDOVANO ZAVIRANJE IZRAŽANJA GENA VIRUSA HEPATITISA B (HBV) Z UPORABO KRATKE INTERFERENČNE NUKLEINSKE KISLINE (siNA) |
| KR102055331B1 (ko) | 2011-04-21 | 2019-12-12 | 아이오니스 파마수티컬즈, 인코포레이티드 | B형 간염 바이러스(hbv) 발현 조절 |
| CN104837501B (zh) | 2012-08-30 | 2018-11-02 | 里普利科股份有限公司 | 治疗乙型肝炎及丁型肝炎感染的方法 |
| US20160296609A1 (en) | 2013-06-28 | 2016-10-13 | Baylor Research Institute | Dendritic cell asgpr targeting immunotherapeutics for multiple sclerosis |
| WO2015089465A1 (en) | 2013-12-12 | 2015-06-18 | The Broad Institute Inc. | Delivery, use and therapeutic applications of the crispr-cas systems and compositions for hbv and viral diseases and disorders |
| JOP20200092A1 (ar) | 2014-11-10 | 2017-06-16 | Alnylam Pharmaceuticals Inc | تركيبات iRNA لفيروس الكبد B (HBV) وطرق لاستخدامها |
| HK1251010A1 (zh) * | 2015-05-06 | 2019-01-18 | Benitec IP Holdings Inc. | 用於治疗乙型肝炎病毒(hbv)感染的试剂及用途 |
| US20170137821A1 (en) | 2015-07-17 | 2017-05-18 | Arcturus Therapeutics, Inc. | Molecules and agents for treating hepatitis b virus |
| CN108136206B (zh) | 2015-07-17 | 2021-10-15 | 阿克丘勒斯治疗公司 | 抗乙型肝炎病毒的组合物和药剂及其用途 |
| MX2018010830A (es) | 2016-03-14 | 2019-02-07 | Hoffmann La Roche | Oligonucleotidos para reducir la expresion de pd-l1. |
| MA45496A (fr) | 2016-06-17 | 2019-04-24 | Hoffmann La Roche | Molécules d'acide nucléique pour la réduction de l'arnm de padd5 ou pad7 pour le traitement d'une infection par l'hépatite b |
| EP3548005A4 (en) | 2016-11-29 | 2020-06-17 | Puretech Health LLC | Exosomes for delivery of therapeutic agents |
| US11324820B2 (en) | 2017-04-18 | 2022-05-10 | Alnylam Pharmaceuticals, Inc. | Methods for the treatment of subjects having a hepatitis b virus (HBV) infection |
| WO2019051812A1 (zh) * | 2017-09-15 | 2019-03-21 | 深圳华大智造科技有限公司 | 确定预定染色体保守区域的方法、确定样本基因组中是否存在拷贝数变异的方法、系统和计算机可读介质 |
| RU2766360C2 (ru) | 2017-10-16 | 2022-03-15 | Ф. Хоффманн-Ля Рош Аг | МОЛЕКУЛЫ НУКЛЕИНОВЫХ КИСЛОТ ДЛЯ УМЕНЬШЕНИЯ УРОВНЯ мРНК PAPD5 ИЛИ PAPD7 ДЛЯ ЛЕЧЕНИЯ ИНФЕКЦИОННОГО ГЕПАТИТА В |
| BR112020020220A8 (pt) | 2018-04-05 | 2021-02-17 | Centre Leon Berard | uso de inibidores da fubp1 para o tratamento de infecção pelo vírus da hepatite b |
| CA3103054A1 (en) | 2018-07-03 | 2020-01-09 | F. Hoffmann-La Roche Ag | Oligonucleotides for modulating tau expression |
| JP7616987B2 (ja) | 2018-07-13 | 2025-01-17 | エフ． ホフマン－ラ ロシュ アーゲー | Ｒｔｅｌ１発現の調節用のオリゴヌクレオチド |
| JP7625512B2 (ja) | 2018-08-13 | 2025-02-03 | アルナイラム ファーマシューティカルズ， インコーポレイテッド | Ｂ型肝炎ウイルス（ＨＢＶ）ｄｓＲＮＡ物質組成物およびその使用方法 |
| CN114867856A (zh) | 2019-12-19 | 2022-08-05 | 豪夫迈·罗氏有限公司 | Saraf抑制剂用于治疗乙型肝炎病毒感染的用途 |
| JP2023506550A (ja) | 2019-12-19 | 2023-02-16 | エフ． ホフマン－ラ ロシュ エージー． | Ｂ型肝炎ウイルス感染症を処置するためのｓｂｄｓ阻害剤の使用 |
| EP4077667A1 (en) | 2019-12-19 | 2022-10-26 | F. Hoffmann-La Roche AG | Use of sept9 inhibitors for treating hepatitis b virus infection |
| CN114829599A (zh) | 2019-12-19 | 2022-07-29 | 豪夫迈·罗氏有限公司 | Scamp3抑制剂用于治疗乙型肝炎病毒感染的用途 |
| EP4077670A1 (en) | 2019-12-19 | 2022-10-26 | F. Hoffmann-La Roche AG | Use of cops3 inhibitors for treating hepatitis b virus infection |
| JP2023538630A (ja) | 2020-08-21 | 2023-09-08 | エフ． ホフマン－ラ ロシュ アーゲー | Ｂ型肝炎ウイルス感染症を処置するためのａ１ｃｆ阻害剤の使用 |
| TW202246500A (zh) | 2021-02-02 | 2022-12-01 | 瑞士商赫孚孟拉羅股份公司 | 用於抑制 ｒｔｅｌ１ 表現之增強型寡核苷酸 |
| CN119095603A (zh) | 2021-12-17 | 2024-12-06 | 豪夫迈·罗氏有限公司 | 用于调节rtel1和fubp1的寡核苷酸的组合 |
Family Cites Families (47)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5643771A (en) | 1980-05-19 | 1997-07-01 | The Board Of Trustees Of The Leland Stanford Junior University | Non-reverting live bacterial vaccines |
| US4897355A (en) | 1985-01-07 | 1990-01-30 | Syntex (U.S.A.) Inc. | N[ω,(ω-1)-dialkyloxy]- and N-[ω,(ω-1)-dialkenyloxy]-alk-1-yl-N,N,N-tetrasubstituted ammonium lipids and uses therefor |
| ATE152169T1 (de) | 1988-02-05 | 1997-05-15 | Whitehead Biomedical Inst | Modifizierte hepatozyten und deren anwendung |
| US5703055A (en) | 1989-03-21 | 1997-12-30 | Wisconsin Alumni Research Foundation | Generation of antibodies through lipid mediated DNA delivery |
| US5279833A (en) | 1990-04-04 | 1994-01-18 | Yale University | Liposomal transfection of nucleic acids into animal cells |
| US5264618A (en) | 1990-04-19 | 1993-11-23 | Vical, Inc. | Cationic lipids for intracellular delivery of biologically active molecules |
| AU652566B2 (en) | 1990-06-18 | 1994-09-01 | United States of America, as represented by the Secretary, U.S. Department of Commerce, The | Eukaryotic expression vector system |
| US5283185A (en) | 1991-08-28 | 1994-02-01 | University Of Tennessee Research Corporation | Method for delivering nucleic acids into cells |
| US20030206887A1 (en) * | 1992-05-14 | 2003-11-06 | David Morrissey | RNA interference mediated inhibition of hepatitis B virus (HBV) using short interfering nucleic acid (siNA) |
| US5593972A (en) | 1993-01-26 | 1997-01-14 | The Wistar Institute | Genetic immunization |
| US5739118A (en) | 1994-04-01 | 1998-04-14 | Apollon, Inc. | Compositions and methods for delivery of genetic material |
| EP0759979A4 (en) * | 1994-05-10 | 1999-10-20 | Gen Hospital Corp | THE ANTISENSE INHIBITION OF HEPATITIS C VIRUS |
| JPH07303485A (ja) | 1994-05-13 | 1995-11-21 | Tonen Corp | Ｈｃｖアンチセンスｒｎａ、それを含む発現ベクター、及び該ｒｎａ又は発現ベクターを含むｈｃｖ関連疾患治療剤 |
| US5646262A (en) * | 1994-07-28 | 1997-07-08 | Georgetown University | Antisense oligonucleotides against hepatitis B viral replication |
| US5837533A (en) | 1994-09-28 | 1998-11-17 | American Home Products Corporation | Complexes comprising a nucleic acid bound to a cationic polyamine having an endosome disruption agent |
| US5571026A (en) * | 1994-12-09 | 1996-11-05 | Kcs Industries, Inc. | Flat mount electrode socket |
| US6057153A (en) * | 1995-01-13 | 2000-05-02 | Yale University | Stabilized external guide sequences |
| US5877159A (en) | 1995-05-03 | 1999-03-02 | University Of Maryland At Baltimore | Method for introducing and expressing genes in animal cells and live invasive bacterial vectors for use in the same |
| US5932241A (en) | 1995-06-07 | 1999-08-03 | Valentis, Incorporated | Cationic lipid DNA complexes for gene targeting |
| US5824538A (en) | 1995-09-06 | 1998-10-20 | The United States Of America As Represented By The Secretary Of The Army | Shigella vector for delivering DNA to a mammalian cell |
| US5843770A (en) * | 1996-03-11 | 1998-12-01 | The Immune Response Corporation | Antisense constructs directed against viral post-transcriptional regulatory sequences |
| US5877162A (en) * | 1996-03-14 | 1999-03-02 | Innovir Laboratories, Inc. | Short external guide sequences |
| US6610478B1 (en) * | 1996-08-16 | 2003-08-26 | Yale University | Phenotypic conversion of cells mediated by external guide sequences |
| US5981274A (en) * | 1996-09-18 | 1999-11-09 | Tyrrell; D. Lorne J. | Recombinant hepatitis virus vectors |
| US6217900B1 (en) | 1997-04-30 | 2001-04-17 | American Home Products Corporation | Vesicular complexes and methods of making and using the same |
| DE19725803C1 (de) * | 1997-06-18 | 1999-02-11 | Deutsches Krebsforsch | HBV-gerichtete Antisense-Nukleinsäuren |
| WO1999037805A1 (en) * | 1998-01-27 | 1999-07-29 | Cytocell Limited | Method for detection of nucleic acid target sequences involving in vitro transcription from an rna promoter |
| US6482804B1 (en) | 1997-10-28 | 2002-11-19 | Wyeth | Compositions and methods for delivery of genetic material |
| US6506559B1 (en) | 1997-12-23 | 2003-01-14 | Carnegie Institute Of Washington | Genetic inhibition by double-stranded RNA |
| KR20010041902A (ko) | 1998-03-16 | 2001-05-25 | 데이비드 엠 모이어 | 포유류의 피부 내의 셀룰라이트를 감소시키는 방법 |
| IL145778A0 (en) | 1999-04-21 | 2002-07-25 | American Home Prod | Methods and compositions for inhibiting the function of polynucleotide sequences |
| US6533250B2 (en) | 1999-10-15 | 2003-03-18 | W. Eugene Arthur | Energy dissipating system for a concrete roadway barrier |
| WO2003070918A2 (en) * | 2002-02-20 | 2003-08-28 | Ribozyme Pharmaceuticals, Incorporated | Rna interference by modified short interfering nucleic acid |
| DE60140676D1 (de) * | 2000-03-30 | 2010-01-14 | Massachusetts Inst Technology | Mediatoren von rns-interferenz, die rns-sequenzspezifisch sind |
| US7439016B1 (en) * | 2000-06-15 | 2008-10-21 | Digene Corporation | Detection of nucleic acids by type-specific hybrid capture method |
| US6680059B2 (en) * | 2000-08-29 | 2004-01-20 | Tripep Ab | Vaccines containing ribavirin and methods of use thereof |
| US6443403B1 (en) | 2000-09-11 | 2002-09-03 | Panduit Corp. | Cable routing clamp and method of application |
| JP2002335968A (ja) * | 2001-05-16 | 2002-11-26 | Kokuritsu Iyakuhin Shokuhin Eisei Kenkyusho | 新規転写因子、その遺伝子及びその結合ｄｎａ配列 |
| EP1412371B1 (en) | 2001-07-12 | 2016-02-24 | University of Massachusetts | IN VIVO PRODUCTION OF SMALL INTERFERING RNAs THAT MEDIATE GENE SILENCING |
| AU2002321859A1 (en) | 2001-08-03 | 2003-02-24 | Michael Van Der Sleesen | Protective garment |
| US7103761B2 (en) | 2001-08-07 | 2006-09-05 | Hewlett-Packard Development Company, Lp. | Server system with multiple management user interfaces |
| US6673661B1 (en) | 2002-12-20 | 2004-01-06 | Taiwan Semiconductor Manufacturing Co., Ltd. | Self-aligned method for forming dual gate thin film transistor (TFT) device |
| EP2071030A3 (en) | 2003-01-24 | 2009-07-22 | Tokyo Metropolitan Organization for Medical Research | Oligoribonucleotide or peptide nucleic acid which inhibits action of hepatitis C virus |
| CN1257284C (zh) | 2003-03-05 | 2006-05-24 | 北京博奥生物芯片有限责任公司 | 一种体外阻断乙肝病毒表达的方法 |
| SG173218A1 (en) | 2003-06-12 | 2011-08-29 | Alnylam Pharmaceuticals Inc | Conserved hbv and hcv sequences useful for gene silencing |
| CA2577519A1 (en) * | 2004-08-23 | 2006-03-30 | Nucleonics, Inc. | Multiple rna polymerase iii promoter expression constructs |
| JP2015086965A (ja) | 2013-10-31 | 2015-05-07 | 株式会社エクセディ | フライホイール組立体 |
-
2004
- 2004-06-10 SG SG2007044373A patent/SG173218A1/en unknown
- 2004-06-10 EP EP18192425.9A patent/EP3470518A1/en active Pending
- 2004-06-10 SI SI200432456T patent/SI2270162T1/sl unknown
- 2004-06-10 JP JP2006533810A patent/JP4980716B2/ja not_active Expired - Fee Related
- 2004-06-10 AU AU2004263832A patent/AU2004263832B2/en not_active Expired
- 2004-06-10 EP EP04776661A patent/EP1631670B1/en not_active Expired - Lifetime
- 2004-06-10 EP EP10180047A patent/EP2284268A3/en not_active Withdrawn
- 2004-06-10 CN CNA2004800228949A patent/CN1836042A/zh active Pending
- 2004-06-10 US US10/560,377 patent/US8350021B2/en not_active Expired - Fee Related
- 2004-06-10 CA CA3040025A patent/CA3040025C/en not_active Expired - Lifetime
- 2004-06-10 BR BRPI0411219-9A patent/BRPI0411219A/pt not_active Application Discontinuation
- 2004-06-10 CA CA2528510A patent/CA2528510C/en not_active Expired - Lifetime
- 2004-06-10 EP EP10180048.0A patent/EP2270162B1/en not_active Expired - Lifetime
- 2004-06-10 HU HUE10180048A patent/HUE042261T2/hu unknown
- 2004-06-10 DK DK10180048.0T patent/DK2270162T3/en active
- 2004-06-10 WO PCT/US2004/019229 patent/WO2005014806A2/en not_active Ceased
-
2005
- 2005-11-30 IL IL172268A patent/IL172268A0/en unknown
-
2011
- 2011-07-04 JP JP2011148461A patent/JP5593279B2/ja not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| US8350021B2 (en) | 2013-01-08 |
| US20080070854A1 (en) | 2008-03-20 |
| AU2004263832A1 (en) | 2005-02-17 |
| WO2005014806A3 (en) | 2005-12-01 |
| EP2270162A3 (en) | 2012-05-30 |
| EP2284268A2 (en) | 2011-02-16 |
| IL172268A0 (en) | 2006-04-10 |
| JP2007503474A (ja) | 2007-02-22 |
| AU2004263832B2 (en) | 2010-07-01 |
| EP2284268A3 (en) | 2012-05-30 |
| CN1836042A (zh) | 2006-09-20 |
| WO2005014806A2 (en) | 2005-02-17 |
| EP2270162A2 (en) | 2011-01-05 |
| EP2270162B1 (en) | 2018-10-03 |
| JP5593279B2 (ja) | 2014-09-17 |
| BRPI0411219A (pt) | 2006-07-18 |
| CA3040025A1 (en) | 2005-02-17 |
| EP1631670A2 (en) | 2006-03-08 |
| SI2270162T1 (sl) | 2019-03-29 |
| EP3470518A1 (en) | 2019-04-17 |
| JP2011224013A (ja) | 2011-11-10 |
| CA3040025C (en) | 2023-01-10 |
| HUE042261T2 (hu) | 2019-06-28 |
| CA2528510A1 (en) | 2005-02-17 |
| SG173218A1 (en) | 2011-08-29 |
| JP4980716B2 (ja) | 2012-07-18 |
| EP1631670B1 (en) | 2012-08-08 |
| CA2528510C (en) | 2019-06-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DK2270162T3 (en) | PRESERVED HBV AND HCV SEQUENCES USED FOR GEN-SILENCING | |
| US10982212B2 (en) | Conserved HBV and HCV sequences useful for gene silencing | |
| JP5934310B2 (ja) | 遺伝子サイレンシングに有用なｈｂｖおよびｈｃｖ保存配列 | |
| US20100063132A1 (en) | Small interfering rna and pharmaceutical composition for treatment of hepatitis b comprising the same | |
| AU2018200873B2 (en) | Conserved HBV and HCV sequences useful for gene silencing | |
| AU2013257445B2 (en) | Conserved HBV and HCV sequences useful for gene silencing | |
| AU2012202085A1 (en) | Conserved HBV and HCV sequences useful for gene silencing |