KR20180052703A - Lpa의 유전자 발현을 저해하기 위한 조성물 및 방법 - Google Patents
Lpa의 유전자 발현을 저해하기 위한 조성물 및 방법 Download PDFInfo
- Publication number
- KR20180052703A KR20180052703A KR1020187010095A KR20187010095A KR20180052703A KR 20180052703 A KR20180052703 A KR 20180052703A KR 1020187010095 A KR1020187010095 A KR 1020187010095A KR 20187010095 A KR20187010095 A KR 20187010095A KR 20180052703 A KR20180052703 A KR 20180052703A
- Authority
- KR
- South Korea
- Prior art keywords
- base
- modified
- mod
- lpa rnai
- seq
- Prior art date
Links
- 108010033266 Lipoprotein(a) Proteins 0.000 title claims abstract description 879
- 230000014509 gene expression Effects 0.000 title claims abstract description 43
- 230000002401 inhibitory effect Effects 0.000 title claims abstract description 6
- 238000000034 method Methods 0.000 title claims description 35
- 239000000203 mixture Substances 0.000 title claims description 17
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 claims abstract description 914
- 230000009368 gene silencing by RNA Effects 0.000 claims abstract description 914
- 239000000463 material Substances 0.000 claims abstract description 309
- 239000000126 substance Substances 0.000 claims abstract description 29
- 239000003814 drug Substances 0.000 claims abstract description 18
- 229940124597 therapeutic agent Drugs 0.000 claims abstract description 12
- 210000003494 hepatocyte Anatomy 0.000 claims abstract description 7
- 239000002777 nucleoside Substances 0.000 claims description 819
- 239000003795 chemical substances by application Substances 0.000 claims description 586
- 230000000692 anti-sense effect Effects 0.000 claims description 512
- 108091081021 Sense strand Proteins 0.000 claims description 319
- 125000003729 nucleotide group Chemical group 0.000 claims description 268
- 239000002773 nucleotide Substances 0.000 claims description 234
- 210000004027 cell Anatomy 0.000 claims description 51
- 230000008685 targeting Effects 0.000 claims description 46
- -1 phosphorothioate nucleoside Chemical class 0.000 claims description 26
- 229930182830 galactose Natural products 0.000 claims description 20
- 239000003446 ligand Substances 0.000 claims description 16
- 102000005427 Asialoglycoprotein Receptor Human genes 0.000 claims description 13
- 108010006523 asialoglycoprotein receptor Proteins 0.000 claims description 13
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 9
- 239000013003 healing agent Substances 0.000 claims description 7
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 claims description 6
- 101100239890 Candida albicans (strain SC5314 / ATCC MYA-2876) NAG4 gene Proteins 0.000 claims description 4
- 125000001921 locked nucleotide group Chemical group 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 3
- 230000035876 healing Effects 0.000 claims description 2
- 101001024442 Cellulomonas fimi Beta-N-acetylglucosaminidase/beta-glucosidase Proteins 0.000 claims 1
- 230000000269 nucleophilic effect Effects 0.000 claims 1
- 229940071643 prefilled syringe Drugs 0.000 claims 1
- 102100040214 Apolipoprotein(a) Human genes 0.000 abstract description 895
- 101710115418 Apolipoprotein(a) Proteins 0.000 abstract description 35
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 20
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 20
- 108090000623 proteins and genes Proteins 0.000 abstract description 18
- 238000011282 treatment Methods 0.000 abstract description 14
- 201000010099 disease Diseases 0.000 abstract description 12
- 101150091521 lpa gene Proteins 0.000 abstract description 12
- 230000005764 inhibitory process Effects 0.000 abstract description 11
- 230000002526 effect on cardiovascular system Effects 0.000 abstract 2
- 108020004414 DNA Proteins 0.000 description 432
- 150000003833 nucleoside derivatives Chemical class 0.000 description 199
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 179
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 136
- 229920000642 polymer Polymers 0.000 description 46
- 238000003197 gene knockdown Methods 0.000 description 40
- 125000005647 linker group Chemical group 0.000 description 33
- 241000699670 Mus sp. Species 0.000 description 32
- 101710119581 Melittin-like peptide Proteins 0.000 description 28
- 238000007920 subcutaneous administration Methods 0.000 description 26
- 210000002966 serum Anatomy 0.000 description 24
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical class 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 22
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- 230000000295 complement effect Effects 0.000 description 21
- 150000002256 galaktoses Chemical class 0.000 description 21
- 108020004999 messenger RNA Proteins 0.000 description 21
- 210000001519 tissue Anatomy 0.000 description 21
- 241000699666 Mus <mouse, genus> Species 0.000 description 20
- 235000018734 Sambucus australis Nutrition 0.000 description 20
- 244000180577 Sambucus australis Species 0.000 description 20
- 239000007924 injection Substances 0.000 description 20
- 238000002347 injection Methods 0.000 description 20
- 238000001990 intravenous administration Methods 0.000 description 20
- 208000002249 Diabetes Complications Diseases 0.000 description 16
- 206010012655 Diabetic complications Diseases 0.000 description 16
- 241001465754 Metazoa Species 0.000 description 16
- 125000006850 spacer group Chemical group 0.000 description 16
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 15
- 238000001727 in vivo Methods 0.000 description 14
- 239000011780 sodium chloride Substances 0.000 description 14
- 201000001320 Atherosclerosis Diseases 0.000 description 13
- MBLBDJOUHNCFQT-UHFFFAOYSA-N N-acetyl-D-galactosamine Natural products CC(=O)NC(C=O)C(O)C(O)C(O)CO MBLBDJOUHNCFQT-UHFFFAOYSA-N 0.000 description 13
- 230000000875 corresponding effect Effects 0.000 description 13
- 235000018102 proteins Nutrition 0.000 description 13
- 102000004169 proteins and genes Human genes 0.000 description 13
- 239000000243 solution Substances 0.000 description 13
- 108091028043 Nucleic acid sequence Proteins 0.000 description 12
- 150000002632 lipids Chemical group 0.000 description 12
- 239000003981 vehicle Substances 0.000 description 11
- OVRNDRQMDRJTHS-CBQIKETKSA-N N-Acetyl-D-Galactosamine Chemical compound CC(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-CBQIKETKSA-N 0.000 description 10
- 241000288906 Primates Species 0.000 description 10
- 235000012000 cholesterol Nutrition 0.000 description 10
- 239000013612 plasmid Substances 0.000 description 10
- 230000009467 reduction Effects 0.000 description 10
- 241000282567 Macaca fascicularis Species 0.000 description 9
- 239000000872 buffer Substances 0.000 description 9
- 108091033319 polynucleotide Proteins 0.000 description 9
- 102000040430 polynucleotide Human genes 0.000 description 9
- 239000002157 polynucleotide Substances 0.000 description 9
- 231100000419 toxicity Toxicity 0.000 description 9
- 230000001988 toxicity Effects 0.000 description 9
- 208000004476 Acute Coronary Syndrome Diseases 0.000 description 8
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 8
- 230000008901 benefit Effects 0.000 description 8
- 210000004369 blood Anatomy 0.000 description 8
- 239000008280 blood Substances 0.000 description 8
- 208000035475 disorder Diseases 0.000 description 8
- 238000000338 in vitro Methods 0.000 description 8
- 238000012546 transfer Methods 0.000 description 8
- 101000889990 Homo sapiens Apolipoprotein(a) Proteins 0.000 description 7
- 108090000765 processed proteins & peptides Proteins 0.000 description 7
- 239000013638 trimer Substances 0.000 description 7
- 210000003462 vein Anatomy 0.000 description 7
- 108010012927 Apoprotein(a) Proteins 0.000 description 6
- 125000000217 alkyl group Chemical group 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 6
- 125000000623 heterocyclic group Chemical group 0.000 description 6
- 239000002245 particle Substances 0.000 description 6
- 208000003017 Aortic Valve Stenosis Diseases 0.000 description 5
- 208000002251 Dissecting Aneurysm Diseases 0.000 description 5
- 241000282326 Felis catus Species 0.000 description 5
- 208000010159 IgA glomerulonephritis Diseases 0.000 description 5
- 206010021263 IgA nephropathy Diseases 0.000 description 5
- 102000007330 LDL Lipoproteins Human genes 0.000 description 5
- 108010007622 LDL Lipoproteins Proteins 0.000 description 5
- 241000282553 Macaca Species 0.000 description 5
- 208000001145 Metabolic Syndrome Diseases 0.000 description 5
- 241000699660 Mus musculus Species 0.000 description 5
- 108091034117 Oligonucleotide Proteins 0.000 description 5
- 208000005764 Peripheral Arterial Disease Diseases 0.000 description 5
- 208000030831 Peripheral arterial occlusive disease Diseases 0.000 description 5
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 5
- 206010002895 aortic dissection Diseases 0.000 description 5
- 206010002906 aortic stenosis Diseases 0.000 description 5
- 201000002064 aortic valve insufficiency Diseases 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 208000029078 coronary artery disease Diseases 0.000 description 5
- 239000002502 liposome Substances 0.000 description 5
- 150000007523 nucleic acids Chemical class 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 238000011830 transgenic mouse model Methods 0.000 description 5
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 4
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 108010052090 Renilla Luciferases Proteins 0.000 description 4
- 201000007527 Retinal artery occlusion Diseases 0.000 description 4
- 206010045261 Type IIa hyperlipidaemia Diseases 0.000 description 4
- 208000026106 cerebrovascular disease Diseases 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000012750 in vivo screening Methods 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 239000000693 micelle Substances 0.000 description 4
- RHLMXWCISNJNDH-UHFFFAOYSA-N n-[2-[3-[[5-[3-(dimethylcarbamoyl)phenyl]-2-methoxyphenyl]sulfonylamino]anilino]ethyl]-3-methylbenzamide Chemical compound COC1=CC=C(C=2C=C(C=CC=2)C(=O)N(C)C)C=C1S(=O)(=O)NC(C=1)=CC=CC=1NCCNC(=O)C1=CC=CC(C)=C1 RHLMXWCISNJNDH-UHFFFAOYSA-N 0.000 description 4
- 239000002105 nanoparticle Substances 0.000 description 4
- 102000039446 nucleic acids Human genes 0.000 description 4
- 108020004707 nucleic acids Proteins 0.000 description 4
- 238000012216 screening Methods 0.000 description 4
- 239000004055 small Interfering RNA Substances 0.000 description 4
- 229940035893 uracil Drugs 0.000 description 4
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 description 3
- 229930024421 Adenine Natural products 0.000 description 3
- 208000030673 Homozygous familial hypercholesterolemia Diseases 0.000 description 3
- 208000031226 Hyperlipidaemia Diseases 0.000 description 3
- 208000004531 Renal Artery Obstruction Diseases 0.000 description 3
- 206010038378 Renal artery stenosis Diseases 0.000 description 3
- 208000007718 Stable Angina Diseases 0.000 description 3
- 208000007814 Unstable Angina Diseases 0.000 description 3
- 206010047249 Venous thrombosis Diseases 0.000 description 3
- 239000008186 active pharmaceutical agent Substances 0.000 description 3
- 229960000643 adenine Drugs 0.000 description 3
- 230000003143 atherosclerotic effect Effects 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 229940104302 cytosine Drugs 0.000 description 3
- 239000005547 deoxyribonucleotide Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 208000020346 hyperlipoproteinemia Diseases 0.000 description 3
- 210000005229 liver cell Anatomy 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 238000010606 normalization Methods 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 150000008300 phosphoramidites Chemical class 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 238000011321 prophylaxis Methods 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 229940126586 small molecule drug Drugs 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 230000001052 transient effect Effects 0.000 description 3
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 2
- FZWGECJQACGGTI-UHFFFAOYSA-N 2-amino-7-methyl-1,7-dihydro-6H-purin-6-one Chemical compound NC1=NC(O)=C2N(C)C=NC2=N1 FZWGECJQACGGTI-UHFFFAOYSA-N 0.000 description 2
- 125000002103 4,4'-dimethoxytriphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)(C1=C([H])C([H])=C(OC([H])([H])[H])C([H])=C1[H])C1=C([H])C([H])=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 2
- RYVNIFSIEDRLSJ-UHFFFAOYSA-N 5-(hydroxymethyl)cytosine Chemical compound NC=1NC(=O)N=CC=1CO RYVNIFSIEDRLSJ-UHFFFAOYSA-N 0.000 description 2
- PEHVGBZKEYRQSX-UHFFFAOYSA-N 7-deaza-adenine Chemical compound NC1=NC=NC2=C1C=CN2 PEHVGBZKEYRQSX-UHFFFAOYSA-N 0.000 description 2
- HCGHYQLFMPXSDU-UHFFFAOYSA-N 7-methyladenine Chemical compound C1=NC(N)=C2N(C)C=NC2=N1 HCGHYQLFMPXSDU-UHFFFAOYSA-N 0.000 description 2
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 2
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 2
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 2
- 108010082126 Alanine transaminase Proteins 0.000 description 2
- 108010088751 Albumins Proteins 0.000 description 2
- 102000009027 Albumins Human genes 0.000 description 2
- 206010002388 Angina unstable Diseases 0.000 description 2
- 102100025668 Angiopoietin-related protein 3 Human genes 0.000 description 2
- 102100030970 Apolipoprotein C-III Human genes 0.000 description 2
- 206010003210 Arteriosclerosis Diseases 0.000 description 2
- 108010002913 Asialoglycoproteins Proteins 0.000 description 2
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 2
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 2
- 101500014077 Bombina orientalis C-terminal extension peptide Proteins 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical group C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 2
- 239000005977 Ethylene Substances 0.000 description 2
- 108090000331 Firefly luciferases Proteins 0.000 description 2
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 2
- 101000693085 Homo sapiens Angiopoietin-related protein 3 Proteins 0.000 description 2
- 101000793223 Homo sapiens Apolipoprotein C-III Proteins 0.000 description 2
- 206010022680 Intestinal ischaemia Diseases 0.000 description 2
- 239000012097 Lipofectamine 2000 Substances 0.000 description 2
- 108010036176 Melitten Proteins 0.000 description 2
- 208000004535 Mesenteric Ischemia Diseases 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- 108700011259 MicroRNAs Proteins 0.000 description 2
- 241001529936 Murinae Species 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 108090000854 Oxidoreductases Proteins 0.000 description 2
- 229940127355 PCSK9 Inhibitors Drugs 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 208000031481 Pathologic Constriction Diseases 0.000 description 2
- 108091093037 Peptide nucleic acid Proteins 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
- 108091028664 Ribonucleotide Proteins 0.000 description 2
- 108091027967 Small hairpin RNA Proteins 0.000 description 2
- 108020004459 Small interfering RNA Proteins 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 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 2
- 239000000443 aerosol Substances 0.000 description 2
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 2
- 150000001408 amides Chemical group 0.000 description 2
- 238000000137 annealing Methods 0.000 description 2
- 239000002214 arabinonucleotide Substances 0.000 description 2
- 208000011775 arteriosclerosis disease Diseases 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 125000003636 chemical group Chemical group 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
- GOHCTCOGYKAJLZ-UHFFFAOYSA-N ctep Chemical compound CC=1N(C=2C=CC(OC(F)(F)F)=CC=2)C(C)=NC=1C#CC1=CC=NC(Cl)=C1 GOHCTCOGYKAJLZ-UHFFFAOYSA-N 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 238000010864 dual luciferase reporter gene assay Methods 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- OLNTVTPDXPETLC-XPWALMASSA-N ezetimibe Chemical compound N1([C@@H]([C@H](C1=O)CC[C@H](O)C=1C=CC(F)=CC=1)C=1C=CC(O)=CC=1)C1=CC=C(F)C=C1 OLNTVTPDXPETLC-XPWALMASSA-N 0.000 description 2
- 229960000815 ezetimibe Drugs 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 2
- 102000045903 human LPA Human genes 0.000 description 2
- 238000009396 hybridization Methods 0.000 description 2
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
- 201000004332 intermediate coronary syndrome Diseases 0.000 description 2
- 238000007917 intracranial administration Methods 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 239000002679 microRNA Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 235000001968 nicotinic acid Nutrition 0.000 description 2
- 229960003512 nicotinic acid Drugs 0.000 description 2
- 239000011664 nicotinic acid Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 125000004437 phosphorous atom Chemical group 0.000 description 2
- 229920000768 polyamine Polymers 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- HEBKCHPVOIAQTA-ZXFHETKHSA-N ribitol Chemical group OC[C@H](O)[C@H](O)[C@H](O)CO HEBKCHPVOIAQTA-ZXFHETKHSA-N 0.000 description 2
- 239000002336 ribonucleotide Substances 0.000 description 2
- 125000002652 ribonucleotide group Chemical group 0.000 description 2
- 238000003998 size exclusion chromatography high performance liquid chromatography Methods 0.000 description 2
- 208000037804 stenosis Diseases 0.000 description 2
- 230000036262 stenosis Effects 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- AVBGNFCMKJOFIN-UHFFFAOYSA-N triethylammonium acetate Chemical compound CC(O)=O.CCN(CC)CC AVBGNFCMKJOFIN-UHFFFAOYSA-N 0.000 description 2
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 2
- DZGWFCGJZKJUFP-UHFFFAOYSA-N tyramine Chemical compound NCCC1=CC=C(O)C=C1 DZGWFCGJZKJUFP-UHFFFAOYSA-N 0.000 description 2
- 229960005486 vaccine Drugs 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- YIMATHOGWXZHFX-WCTZXXKLSA-N (2r,3r,4r,5r)-5-(hydroxymethyl)-3-(2-methoxyethoxy)oxolane-2,4-diol Chemical compound COCCO[C@H]1[C@H](O)O[C@H](CO)[C@H]1O YIMATHOGWXZHFX-WCTZXXKLSA-N 0.000 description 1
- FYADHXFMURLYQI-UHFFFAOYSA-N 1,2,4-triazine Chemical class C1=CN=NC=N1 FYADHXFMURLYQI-UHFFFAOYSA-N 0.000 description 1
- UHUHBFMZVCOEOV-UHFFFAOYSA-N 1h-imidazo[4,5-c]pyridin-4-amine Chemical compound NC1=NC=CC2=C1N=CN2 UHUHBFMZVCOEOV-UHFFFAOYSA-N 0.000 description 1
- QSHACTSJHMKXTE-UHFFFAOYSA-N 2-(2-aminopropyl)-7h-purin-6-amine Chemical compound CC(N)CC1=NC(N)=C2NC=NC2=N1 QSHACTSJHMKXTE-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-GASJEMHNSA-N 2-amino-2-deoxy-D-galactopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O MSWZFWKMSRAUBD-GASJEMHNSA-N 0.000 description 1
- GXGKKIPUFAHZIZ-UHFFFAOYSA-N 5-benzylsulfanyl-2h-tetrazole Chemical compound C=1C=CC=CC=1CSC=1N=NNN=1 GXGKKIPUFAHZIZ-UHFFFAOYSA-N 0.000 description 1
- LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical compound CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 description 1
- LKDWQHQNDDNHSC-UHFFFAOYSA-N 5-phenyl-1,2,4-dithiazol-3-one Chemical compound S1SC(=O)N=C1C1=CC=CC=C1 LKDWQHQNDDNHSC-UHFFFAOYSA-N 0.000 description 1
- UJBCLAXPPIDQEE-UHFFFAOYSA-N 5-prop-1-ynyl-1h-pyrimidine-2,4-dione Chemical compound CC#CC1=CNC(=O)NC1=O UJBCLAXPPIDQEE-UHFFFAOYSA-N 0.000 description 1
- KXBCLNRMQPRVTP-UHFFFAOYSA-N 6-amino-1,5-dihydroimidazo[4,5-c]pyridin-4-one Chemical compound O=C1NC(N)=CC2=C1N=CN2 KXBCLNRMQPRVTP-UHFFFAOYSA-N 0.000 description 1
- DCPSTSVLRXOYGS-UHFFFAOYSA-N 6-amino-1h-pyrimidine-2-thione Chemical compound NC1=CC=NC(S)=N1 DCPSTSVLRXOYGS-UHFFFAOYSA-N 0.000 description 1
- LOSIULRWFAEMFL-UHFFFAOYSA-N 7-deazaguanine Chemical compound O=C1NC(N)=NC2=C1CC=N2 LOSIULRWFAEMFL-UHFFFAOYSA-N 0.000 description 1
- LPXQRXLUHJKZIE-UHFFFAOYSA-N 8-azaguanine Chemical compound NC1=NC(O)=C2NN=NC2=N1 LPXQRXLUHJKZIE-UHFFFAOYSA-N 0.000 description 1
- 229960005508 8-azaguanine Drugs 0.000 description 1
- MSSXOMSJDRHRMC-UHFFFAOYSA-N 9H-purine-2,6-diamine Chemical compound NC1=NC(N)=C2NC=NC2=N1 MSSXOMSJDRHRMC-UHFFFAOYSA-N 0.000 description 1
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 101710095342 Apolipoprotein B Proteins 0.000 description 1
- 102100040202 Apolipoprotein B-100 Human genes 0.000 description 1
- 208000031104 Arterial Occlusive disease Diseases 0.000 description 1
- 101150075175 Asgr1 gene Proteins 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- QGOOVYDNNMBCPD-UHFFFAOYSA-N C1(CC1)OP(O)=O Chemical compound C1(CC1)OP(O)=O QGOOVYDNNMBCPD-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 102100023804 Coagulation factor VII Human genes 0.000 description 1
- 206010069696 Coeliac artery occlusion Diseases 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 239000004593 Epoxy Substances 0.000 description 1
- 108010023321 Factor VII 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
- 241000282412 Homo Species 0.000 description 1
- 101000889953 Homo sapiens Apolipoprotein B-100 Proteins 0.000 description 1
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
- FVMMQJUBNMOPPR-WLDMJGECSA-N N-[(3R,4R,5R,6R)-2,4,5-trihydroxy-6-(hydroxymethyl)oxan-3-yl]formamide Chemical compound OC[C@H]1OC(O)[C@H](NC=O)[C@@H](O)[C@H]1O FVMMQJUBNMOPPR-WLDMJGECSA-N 0.000 description 1
- RTEOJYOKWPEKKN-HXQZNRNWSA-N N-[(3R,4R,5R,6R)-2,4,5-trihydroxy-6-(hydroxymethyl)oxan-3-yl]propanamide Chemical compound CCC(=O)N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O RTEOJYOKWPEKKN-HXQZNRNWSA-N 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- 108010001267 Protein Subunits Proteins 0.000 description 1
- 102000002067 Protein Subunits Human genes 0.000 description 1
- JVWLUVNSQYXYBE-UHFFFAOYSA-N Ribitol Natural products OCC(C)C(O)C(O)CO JVWLUVNSQYXYBE-UHFFFAOYSA-N 0.000 description 1
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- 108091036066 Three prime untranslated region Proteins 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 101150013568 US16 gene Proteins 0.000 description 1
- CKIATKFZBLERNU-UHFFFAOYSA-N [(4-cyano-2-methylbutan-2-yl)-propan-2-ylamino]oxyphosphonamidous acid Chemical compound NP(O)ON(C(C)C)C(C)(C)CCC#N CKIATKFZBLERNU-UHFFFAOYSA-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
- 238000010521 absorption reaction Methods 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- 150000003838 adenosines Chemical class 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 150000001345 alkine derivatives Chemical group 0.000 description 1
- 125000005600 alkyl phosphonate group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 1
- 239000001099 ammonium carbonate Substances 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 238000005571 anion exchange chromatography Methods 0.000 description 1
- 230000000181 anti-adherent effect Effects 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000003911 antiadherent Substances 0.000 description 1
- 229940125681 anticonvulsant agent Drugs 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 208000021328 arterial occlusion Diseases 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 238000012098 association analyses Methods 0.000 description 1
- 239000003212 astringent agent Substances 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- 239000000227 bioadhesive Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- OTBHHUPVCYLGQO-UHFFFAOYSA-N bis(3-aminopropyl)amine Chemical group NCCCNCCCN OTBHHUPVCYLGQO-UHFFFAOYSA-N 0.000 description 1
- 238000009534 blood test Methods 0.000 description 1
- 239000006085 branching agent Substances 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 230000007211 cardiovascular event Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000005289 controlled pore glass Substances 0.000 description 1
- 230000002596 correlated effect Effects 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
- 229940109239 creatinine Drugs 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- 229940097362 cyclodextrins Drugs 0.000 description 1
- FBWJHGIUUCOZRM-UHFFFAOYSA-N cyclopropylphosphonic acid Chemical group OP(O)(=O)C1CC1 FBWJHGIUUCOZRM-UHFFFAOYSA-N 0.000 description 1
- 238000002716 delivery method Methods 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 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
- 239000007884 disintegrant Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000003255 drug test Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- ZTWTYVWXUKTLCP-UHFFFAOYSA-L ethenyl-dioxido-oxo-$l^{5}-phosphane Chemical compound [O-]P([O-])(=O)C=C ZTWTYVWXUKTLCP-UHFFFAOYSA-L 0.000 description 1
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 229940012413 factor vii Drugs 0.000 description 1
- 210000003191 femoral vein Anatomy 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- VWVXNHZWIKGQAW-UHFFFAOYSA-N fluorophosphonamidous acid Chemical compound NP(O)F VWVXNHZWIKGQAW-UHFFFAOYSA-N 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000002706 hydrostatic effect Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- VDXZNPDIRNWWCW-JFTDCZMZSA-N melittin Chemical compound NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(N)=O)CC1=CNC2=CC=CC=C12 VDXZNPDIRNWWCW-JFTDCZMZSA-N 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- RXMBKOPBFXCPDD-UHFFFAOYSA-N methoxyphosphonamidous acid Chemical compound COP(N)O RXMBKOPBFXCPDD-UHFFFAOYSA-N 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- RSILPKJOINTLOK-UJRRQQMQSA-N n-[2-[2-[(2r,3r,4r,5r,6r)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyethoxy]ethyl]-3-(4-methyl-2,5-dioxofuran-3-yl)propanamide Chemical compound CC(=O)N[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1OCCOCCNC(=O)CCC1=C(C)C(=O)OC1=O RSILPKJOINTLOK-UJRRQQMQSA-N 0.000 description 1
- 239000002088 nanocapsule Substances 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000008298 phosphoramidates Chemical class 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 150000003141 primary amines Chemical group 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000003571 reporter gene assay Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 239000012146 running buffer Substances 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000005556 structure-activity relationship Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical group NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 description 1
- 125000000565 sulfonamide group Chemical group 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 150000003457 sulfones Chemical group 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- ZEMGGZBWXRYJHK-UHFFFAOYSA-N thiouracil Chemical compound O=C1C=CNC(=S)N1 ZEMGGZBWXRYJHK-UHFFFAOYSA-N 0.000 description 1
- 210000003813 thumb Anatomy 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960003732 tyramine Drugs 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 238000004078 waterproofing Methods 0.000 description 1
- 229940075420 xanthine Drugs 0.000 description 1
Images
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
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- 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
- C12N15/1137—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 enzymes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/21—Serine endopeptidases (3.4.21)
-
- 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 N.A.
-
- 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
- C12N2310/30—Chemical structure
- C12N2310/31—Chemical structure of the backbone
-
- 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
- C12N2310/30—Chemical structure
- C12N2310/31—Chemical structure of the backbone
- C12N2310/315—Phosphorothioates
-
- 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
- C12N2310/30—Chemical structure
- C12N2310/32—Chemical structure of the sugar
- C12N2310/321—2'-O-R Modification
-
- 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
- C12N2310/30—Chemical structure
- C12N2310/35—Nature of the modification
- C12N2310/351—Conjugate
-
- 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
- C12N2310/30—Chemical structure
- C12N2310/35—Nature of the modification
- C12N2310/351—Conjugate
- C12N2310/3517—Marker; Tag
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Microbiology (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Virology (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (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)
- Medicinal Preparation (AREA)
Abstract
LPA(아포(a)) 유전자의 발현을 저해하기 위한 RNA 간섭(RNAi) 물질 및 RNAi 물질 접합체가 기재되어 있다. 임의로 하나 이상의 추가 치유제와 함께 하나 이상의 LPA RNAi 물질을 포함하는 약제학적 조성물이 또한 기재되어 있다. 생체내 간 세포로의 기재된 LPA RNAi 물질의 전달은 LPA 유전자 발현의 저해 및 심혈관 및 심혈관 관련 질환의 치료를 제공한다.
Description
지단백(a)[Lp(a)]은, 지질 코어 및 아포지단백 B(아포B-100)를, 다이설파이드 결합을 통해 아포B-100에 부착된, 아포지단백(a)(아포(a))인 독특한 성분과 함께, 함유하는 불균일 저밀도 지단백(low density lipoprotein: LDL) 유사 입자이다.
아포(a) 유전자(LPA)는 주로 간에서 발현되고, 발현은 인간 및 비인간 영장류로 제한된다. 인간에서의 Lp(a) 수준은 유전적으로 한정되고, 식이, 운동 또는 다른 라이프사이클 변화에 의해 상당히 변하지 않는다. LPA는 존재하는 Kringle KIV2 도메인의 수에 따라 길이가 변하고, 이의 발현은 존재하는 도메인의 수와 역으로 상관된다. 정상 Lp(a) 수준은 0.1 내지 25㎎/㎗의 범위이고, 미합중국에서의 집단의 약 25%는 30㎎/㎗ 이상의 Lp(a) 수준을 가진다.
다수의 연구에서의 Lp(a) 수준의 분석은 심혈관 질환, 뇌졸중 및 다른 관련 장애, 예컨대 죽상동맥경화성 협착증에 대한 독리적 위험 인자로서 높은 Lp(a) 수준을 시사하였다. 또한, 게놈형 회합 분석은 또한 죽상동맥경화성 협착증과 같은 질환에 대한 유전적 위험 인자로서 LPA를 시사하였다.
고지혈증 환자에서 Lp(a) 및 LDL 수준 둘 다를 낮추기 위해 치료학적 지단백 성분채집술을 이용할 때, 심혈관 사건의 상당한 감소가 관찰되었다. 따라서, 이들 및 다른 LPA 관련 질환에 관한 치유제 및 치료제에 대한 수요가 존재한다.
LPA 유전자의 발현을 선택적으로 및 효율적으로 저해하기 위한, LPA(또한 아포(a)라 칭함) RNA 간섭(RNAi) 물질(또한 RNAi 트리거 또는 트리거라 칭함) 및 LPA RNAi 물질을 함유하는 조성물이 본 명세서에 기재되어 있다. LPA는 지단백(a) 입자(Lp(a))의 중요한 성분인 아포지단백(a)(아포(a))을 코딩하는 유전자의 명칭이다. 본 명세서에 기재된 LPA RNAi 물질은, 베르거(Berger) 질환, 말초 동맥 질환, 관상동맥 질환, 대사 증후군, 급성 관상동맥 증후군, 대동맥판막 협착증, 대동맥판막 역류, 대동맥 박리, 망막 동맥 폐쇄, 뇌혈관 질환, 장간막 허혈, 견상장간막 동맥 폐쇄, 신동맥 협착증, 안정/불안정 협심증, 급성 관상동맥 증후군, 이형접합 또는 동형접합 가족성 고콜레스테롤혈증, 고아포베타지단백혈증, 뇌혈관 죽상동맥경화증, 뇌혈관 질환 및 정맥성 혈전증(이들로 제한되지는 않음)을 포함하는, 질환의 예방 또는 치료 또는 이 질환의 예방 또는 치료를 위한 약제의 제조시 사용될 수 있다.
각각의 LPA RNAi 물질은 적어도 센스 가닥 및 안티센스 가닥을 포함한다. 센스 가닥 및 안티센스 가닥은 서로에 부분적으로, 실질적으로 또는 완전히 상보성이다. 본 명세서에 기재된 RNAi 물질 센스 및 안티센스 가닥의 길이는 각각 17개 내지 30개의 뉴클레오타이드 길이일 수 있다. 몇몇 실시형태에서, 센스 및 안티센스 가닥은 독립적으로 17개 내지 26개의 뉴클레오타이드 길이이다. 센스 및 안티센스 가닥은 동일한 길이 또는 상이한 길이일 수 있다. 본 명세서에 기재된 RNAi 물질은, LPA 유전자를 발현하는 세포에 전달 시, 시험관내 또는 생체내 LPA 유전자의 발현을 저해한다.
LPA RNAi 물질의 센스 가닥은 LPA mRNA에서의 서열에 적어도 17개의 연속적 뉴클레오타이드의 코어 스트레치에 걸쳐 적어도 90%의 동일성을 가지는 뉴클레오타이드 서열을 포함한다. 몇몇 실시형태에서, LPA mRNA에서의 서열에 적어도 90%의 동일성을 가지는 센스 가닥 뉴클레오타이드 서열은 17개, 18개, 19개, 20개, 21개, 22개 또는 23개의 뉴클레오타이드 길이이다. LPA RNAi 물질의 안티센스 가닥은 LPA mRNA에서의 서열에 적어도 16개의 연속적 뉴클레오타이드의 코어 스트레치 및 상응하는 센스 가닥에 걸쳐 적어도 90%의 상보성을 가지는 뉴클레오타이드 서열을 포함한다. 몇몇 실시형태에서, LPA mRNA에서의 서열에 적어도 90%의 상보성을 가지는 안티센스 가닥 뉴클레오타이드 서열 또는 상응하는 센스 가닥은 17개, 18개, 19개, 20개, 21개, 22개 또는 23개의 뉴클레오타이드 길이이다.
몇몇 실시형태에서, 하나 이상의 LPA RNAi 물질은 당해 분야에 공지된 임의의 올리고뉴클레오타이드 전달 기법을 이용하여 표적 세포 또는 조직으로 전달된다. 핵산 전달 방법은 리포솜에서의 캡슐화에 의한, 이온도입법에 의한, 또는 다른 비히클, 예컨대 하이드로겔, 사이클로덱스트린, 생분해성 나노캡슐 및 생접착성 마이크로구, 단백질성 벡터 또는 Dynamic Polyconjugates(상표명)(DPC)로의 혼입에 의한 것을 포함하지만, 이들로 제한되지는 않는다(예를 들어, WO 제2000/053722호, WO 제2008/0022309호, WO 제2011/104169호 및 WO 제2012/083185호(이들은 각각 본 명세서에 참고로 포함됨) 참조). 몇몇 실시형태에서, LPA RNAi 물질은 표적화기에 접합된다. 몇몇 실시형태에서, 표적화기는 세포 수용체 리간드, 예컨대 갈락토스 클러스터, 예컨대 N-아세틸-갈락토스아민 삼합체를 포함하는 갈락토스 클러스터를 포함할 수 있다.
몇몇 실시형태에서, 하나 이상의 LPA RNAi 물질을 포함하는 약제학적 조성물이 기재되어 있다. 몇몇 실시형태에서, LPA RNAi 물질은 하나 이상의 추가(즉, 제2, 제3 등) 치유제와 임의로 조합된다. 추가 치료제는 또 다른 LPA RNAi 물질(예를 들어, LPA 표적 내에 상이한 서열을 표적화하는 LPA RNAi 물질)일 수 있다. 추가 치료제는 또한 소분자 약물, 항체, 항체 단편 및/또는 백신일 수 있다. 하나 이상의 추가 치유제와 함께 또는 이것 없이 LPA RNAi 물질은 하나 이상의 부형제와 조합되어 약제학적 조성물을 형성할 수 있다.
몇몇 실시형태에서, 표적화기에 접합된, LPA RNAi 물질을 포함하는, 간 세포, 특히 간세포로 LPA RNAi 물질을 전달하기 위한 조성물이 생체내 기재되어 있다. 몇몇 실시형태에서, 표적화기는 아시알로당단백질 리간드이다.
적어도 부분적으로 LPA 발현에 의해 매개된 병리학적 상태를 가지거나 이 병리학적 상태를 발생시킬 위험에 있는 인간 대상체를 치료하는 방법이 또한 기재되어 있고, 상기 방법은 치료학적 유효량의 LPA RNAi 물질 또는 LPA RNAi 물질 함유 조성물을 대상체에게 투여하는 단계(들)를 포함한다. LPA RNAi 물질 또는 LPA RNAi 물질 함유 조성물에 의해 대상체를 치료하는 방법은 하나 이상의 추가(즉, 제2) 치유제 또는 치료를 투여하는 하나 이상의 단계와 임의로 조합될 수 있다. LPA RNAi 물질 및 추가 치유제는 단일 조성물로 투여될 수 있거나, 별개로 투여될 수 있다. 추가 치유제의 예는 HMg Co-A 환원효소 저해제(스타틴), 에제티미브, PCSK-9 저해제, CTEP 저해제, ANGPTL3을 표적화하는 치료제, APOC3을 표적화하는 치료제 및 니아신을 포함하지만, 이들로 제한되지는 않는다.
기재된 LPA RNAi 물질의 사용은 베르거 질환, 말초 동맥 질환, 관상동맥 동맥 질환, 대사 증후군, 급성 관상동맥 증후군, 대동맥판막 협착증, 대동맥판막 역류, 대동맥 박리, 망막 동맥 폐쇄, 뇌혈관 질환, 장간막 허혈, 견상장간막 동맥 폐쇄, 신동맥 협착증, 안정/불안정 협심증, 급성 관상동맥 증후군, 이형접합 또는 동형접합 가족성 고콜레스테롤혈증, 고아포베타지단백혈증, 뇌혈관 죽상동맥경화증, 뇌혈관 질환 및 정맥성 혈전증(이들로 제한되지는 않음)을 포함하는 질환의 치료학적 예방 또는 치료를 위한 방법에서 사용될 수 있다. 이러한 방법은 대상체, 예를 들어, 인간 또는 동물 대상체에 대한 본 명세서에 기재된 바와 같은 LPA RNAi 물질의 투여를 포함한다.
약제학적 조성물은 국소 또는 전신 치료가 원해지는지 및 치료되는 부위에 따라 다수의 방식으로 투여될 수 있다. 투여는 당해 분야에 흔히 공지된 임의의 방식, 예컨대 국소(예를 들어, 경피 패치에 의해), 폐(예를 들어, 분무기에 의한 것을 포함하여, 분말 또는 에어로졸의 흡입 또는 통기법에 의해, 기관내, 비강내), 표피, 경피, 경구 또는 비경구(이들로 제한되지는 않음)에 의해 이루어질 수 있다. 비경구 투여는 정맥내, 동맥내, 피하, 복강내 또는 근육내 주사 또는 점적주사; (예를 들어, 이식 장치를 통한) 피하, 두개내, 뇌실질내, 척추강내 및 심실내 투여를 포함하지만, 이들로 제한되지는 않는다. 몇몇 실시형태에서, 본 명세서에 기재된 약제학적 조성물은 피하 주사에 의해 투여된다.
기재된 LPA RNAi 물질 및/또는 조성물은 베르거 질환, 말초 동맥 질환, 관상동맥 동맥 질환, 대사 증후군, 급성 관상동맥 증후군, 대동맥판막 협착증, 대동맥판막 역류, 대동맥 박리, 망막 동맥 폐쇄, 뇌혈관 질환, 장간막 허혈, 견상장간막 동맥 폐쇄, 신동맥 협착증, 안정/불안정 협심증, 급성 관상동맥 증후군, 이형접합 또는 동형접합 가족성 고콜레스테롤혈증, 고아포베타지단백혈증, 뇌혈관 죽상동맥경화증, 뇌혈관 질환 및 정맥성 혈전증(이들로 제한되지는 않음)을 포함하는 질환의 치료학적 치료를 위한 방법에서 사용될 수 있다. 이러한 방법은 대상체, 예를 들어, 인간 또는 동물 대상체에 대한 본 명세서에 기재된 바와 같은 LPA RNAi 물질의 투여를 포함한다.
다르게 정의되지 않은 한, 본 명세서에 사용된 모든 기술 용어 및 과학 용어는 본 발명이 속하는 분야의 숙련자에 의해 흔히 이해되는 것과 동일한 의미를 가진다. 본 명세서에 기재된 것과 유사하거나 동등한 방법 및 재료가 본 발명의 실행 또는 교시에서 사용될 수 있지만, 적합한 방법 및 재료가 하기 기재되어 있다. 본 명세서에 언급된 모든 공보, 특허 출원, 특허 및 다른 문헌은 그 전문이 참고로 포함된다. 상충의 경우에, 정의를 포함하는 본 명세서가 지배할 것이다. 또한, 재료, 방법 및 예는 오직 예시적이고 제한되도록 의도되지 않는다.
본 발명의 다른 특징 및 이점은 하기 상세한 설명 및 청구항으로부터 명확할 것이다.
도 1. 0.5㎎/㎏(파선) 또는 2㎎/㎏(실선)의 표시된 LPA RNAi 물질의 단일 피하 투여 후 Lp(a) 형질전환(Tg) 마우스에서의 혈청 Lp(a) 단백질 수준을 예시하는 그래프. Lp(a) 수준을 1일 및 식염수 대조군으로 정규화하였다.
도 2. 3주 동안 주 1회 투여된(1일, 8일 및 15일에 투약), 1㎎/㎏(파선) 또는 3㎎/㎏(실선)의 표시된 LPA RNAi 물질의 3의 피하 용량의 투여 후 Lp(a) Tg 마우스에서의 혈청 Lp(a) 단백질 수준을 예시하는 그래프. Lp(a) 수준을 1일 및 식염수 대조군으로 정규화하였다.
도 3. 1일에 전달 중합체와 함께 1:1(중량/중량) 투약된 단일 2㎎/㎏의 AD01196 LPA RNAi 물질의 투여 후 사이노몰거스 원숭이 혈청에서의 Lp(a) 입자 수준을 예시하는 그래프. Lp(a) 수준을 (0일로 표시된) 2의 투약전 값으로 정규화하였다.
도 4. 1일 및 71일에 전달 중합체와 함께 1:1(중량/중량) 투약된 4㎎/㎏ 또는 6㎎/㎏의 LPA RNAi 물질의 투여 후 사이노몰거스 원숭이 혈청에서의 Lp(a) 입자 수준을 예시하는 그래프. Lp(a) 수준을 (0일로 표시된) 2의 투약전 값으로 정규화하였다. 4㎎/㎏ 용량 = 검정 원; 6㎎/㎏ 용량 = 회색 정사각형.
도 5. 1일, 8일 및 15일에 3㎎/㎏의 AD02819 LPA RNAi 물질의 3의 주마다의 피하 용량 후 사이노몰거스 원숭이 혈청에서의 Lp(a) 입자 수준을 예시하는 그래프. Lp(a) 수준을 (0일로 표시된) 3의 투약전 값으로 정규화하였다.
도 6. 1일에 3㎎/㎏의 LPA RNAi 물질의 단일 피하 투여 후 사이노몰거스 원숭이 혈청에서의 Lp(a) 입자 수준을 예시하는 그래프. AD03460 및 AD03536 군은 48일에 추가 1㎎/㎏의 LPA RNAi 물질의 용량을 받았다. Lp(a) 수준을 (0일로 표시된) 3의 투약전 값으로 정규화하였다.
도 2. 3주 동안 주 1회 투여된(1일, 8일 및 15일에 투약), 1㎎/㎏(파선) 또는 3㎎/㎏(실선)의 표시된 LPA RNAi 물질의 3의 피하 용량의 투여 후 Lp(a) Tg 마우스에서의 혈청 Lp(a) 단백질 수준을 예시하는 그래프. Lp(a) 수준을 1일 및 식염수 대조군으로 정규화하였다.
도 3. 1일에 전달 중합체와 함께 1:1(중량/중량) 투약된 단일 2㎎/㎏의 AD01196 LPA RNAi 물질의 투여 후 사이노몰거스 원숭이 혈청에서의 Lp(a) 입자 수준을 예시하는 그래프. Lp(a) 수준을 (0일로 표시된) 2의 투약전 값으로 정규화하였다.
도 4. 1일 및 71일에 전달 중합체와 함께 1:1(중량/중량) 투약된 4㎎/㎏ 또는 6㎎/㎏의 LPA RNAi 물질의 투여 후 사이노몰거스 원숭이 혈청에서의 Lp(a) 입자 수준을 예시하는 그래프. Lp(a) 수준을 (0일로 표시된) 2의 투약전 값으로 정규화하였다. 4㎎/㎏ 용량 = 검정 원; 6㎎/㎏ 용량 = 회색 정사각형.
도 5. 1일, 8일 및 15일에 3㎎/㎏의 AD02819 LPA RNAi 물질의 3의 주마다의 피하 용량 후 사이노몰거스 원숭이 혈청에서의 Lp(a) 입자 수준을 예시하는 그래프. Lp(a) 수준을 (0일로 표시된) 3의 투약전 값으로 정규화하였다.
도 6. 1일에 3㎎/㎏의 LPA RNAi 물질의 단일 피하 투여 후 사이노몰거스 원숭이 혈청에서의 Lp(a) 입자 수준을 예시하는 그래프. AD03460 및 AD03536 군은 48일에 추가 1㎎/㎏의 LPA RNAi 물질의 용량을 받았다. Lp(a) 수준을 (0일로 표시된) 3의 투약전 값으로 정규화하였다.
LPA 유전자의 발현을 저해하기 위한 RNAi 물질(본 명세서에서 LPA RNAi 물질이라 칭함)이 본 명세서에 기재되어 있다. 본 명세서에 기재된 RNAi 물질은, LPA 유전자를 발현하는 세포로의 전달 시, RNA 간섭(RNAi)의 생물학적 과정을 통해 시험관내 및/또는 생체내 LPA의 발현을 저해하거나 넉다운시킨다. 본 명세서에 사용된 바대로, 구체적으로 달리 기재되지 않은 한, LPA는 적절한 경우 LPA 유전자, LPA mRNA 또는 LP(a) 단백질을 의미할 수 있다.
LPA RNAi 물질은 센스 가닥 및 안티센스 가닥을 포함한다. 센스 가닥 및 안티센스 가닥은 각각 코어 서열 17개 내지 23개의 핵염기 길이를 함유한다. 안티센스 가닥 코어 서열은 LPA mRNA에 존재하는 뉴클레오타이드 서열(때때로 예를 들어 표적 서열이라 칭해짐)에 100%(완전히) 상보성 또는 적어도 90%(실질적으로) 상보성이다. 센스 가닥 코어 서열은 안티센스 가닥에서의 서열에 100%(완전히) 상보성 또는 적어도 90%(실질적으로) 상보성이고, 이에 따라 센스 가닥 코어 서열은 LPA mRNA에 존재하는 뉴클레오타이드 서열(표적 서열)에 완전히 동일하거나 적어도 90% 동일하다. 센스 가닥 코어 서열은 상응하는 안티센스 코어 서열과 동일한 길이일 수 있거나, 이것은 상이한 길이일 수 있다. 몇몇 실시형태에서, 안티센스 가닥 코어 서열은 17개, 18개, 19개, 20개, 21개, 22개 또는 23개의 뉴클레오타이드 길이이다. 몇몇 실시형태에서, 센스 가닥 코어 서열은 17개, 18개, 19개, 20개, 21개, 22개 또는 23개의 뉴클레오타이드 길이이다.
LPA RNAi 물질 센스 및 안티센스 가닥은 어닐링하여 듀플렉스를 형성한다. LPA RNAi 물질의 센스 가닥 및 안티센스 가닥은 서로에 부분적으로, 실질적으로 또는 완전히 상보성이다. 상보성 듀플렉스 영역 내에, 센스 가닥 코어 서열은 안티센스 코어 서열에 적어도 90% 상보성 또는 100% 상보성이다. 몇몇 실시형태에서, 센스 가닥 코어 서열은 안티센스 가닥 코어 서열의 상응하는 17개, 18개, 19개, 20개 또는 21개의 뉴클레오타이드 서열에 적어도 90% 또는 100% 상보성인 적어도 17개, 적어도 18개, 적어도 19개, 적어도 20개 또는 적어도 21개의 뉴클레오타이드의 서열을 함유한다(즉, LPA RNAi 물질의 센스 가닥 및 안티센스 코어 서열은 적어도 90%의 쌍지은 염기 또는 100%의 쌍지은 염기인 적어도 17개, 적어도 18개, 적어도 19개, 적어도 20개 또는 적어도 21개의 뉴클레오타이드의 영역을 가진다.)
다르게 표시되지 않은 한, 본 명세서에 사용된 바와 같은, 용어 "상보성"은, 제2 뉴클레오타이드 서열(예를 들어, RNAi 물질 안티센스 가닥)과 관련하여 제1 뉴클레오타이드 서열(예를 들어, RNAi 물질 센스 가닥 또는 LPA mRNA)을 기재하도록 사용될 때, 혼성화하고(염기 쌍 수소 결합을 형성하고), 제2 뉴클레오타이드 서열을 포함하는 올리고뉴클레오타이드 또는 폴리뉴클레오타이드와 소정의 조건 하에 듀플렉스 또는 이중 나선 구조를 형성하는, 제1 뉴클레오타이드 서열을 포함하는 올리고뉴클레오타이드 또는 폴리뉴클레오타이드의 능력을 의미한다. 상보성 서열은 왓슨-클릭(Watson-Crick) 염기 쌍 또는 비-왓슨-클릭 염기 쌍을 포함하고, 혼성화하는 이의 능력과 관련하여 상기 요건이 충족되는 한, 천연 또는 변형된 뉴클레오타이드 또는 뉴클레오타이드 모방체를 포함한다. "완벽히 상보성" 또는 "완전히 상보성"은 제1 폴리뉴클레오타이드의 인접한 서열에서의 모든(100%) 염기가 제2 폴리뉴클레오타이드의 인접한 서열에서의 동일한 수의 염기와 혼성화한다는 것을 의미한다. 인접한 서열은 제1 또는 제2 뉴클레오타이드 서열의 전부 또는 일부를 포함할 수 있다. 본 명세서에 사용된 바와 같은, "부분 상보성"은, 핵염기 서열의 혼성화된 쌍에서, 제1 폴리뉴클레오타이드의 인접한 서열에서의 적어도 70%의 염기가 제2 폴리뉴클레오타이드의 인접한 서열에서의 동일한 수의 염기와 혼성화한다는 것을 의미한다. 본 명세서에 사용된 바와 같은, "실질적인 상보성"은, 핵염기 서열의 혼성화된 쌍에서, 제1 폴리뉴클레오타이드의 인접한 서열에서의 적어도 85%의 염기가 제2 폴리뉴클레오타이드의 인접한 서열에서의 동일한 수의 염기와 혼성화한다는 것을 의미한다. 본 명세서에 사용된 바와 같은, 용어 "상보성", "완전히 상보성" 및 "실질적으로 상보성"은 RNAi 물질의 센스 가닥 및 안티센스 가닥 사이, 또는 RNAi 물질의 안티센스 가닥과 LPA mRNA의 서열 사이의 염기 미스매칭과 관련하여 사용될 수 있다. 서열 동일성 또는 상보성은 변형에 독립적이다. 동일성 또는 상보성을 결정할 목적을 위해, 예를 들어 a 및 Af는 U(또는 T)에 상보성이고, A와 동일하다.
본 명세서에 기재된 LPA RNAi 물질 센스 및 안티센스 가닥의 길이는 독립적으로 17개 내지 30개의 뉴클레오타이드 길이이다. 몇몇 실시형태에서, 센스 및 안티센스 가닥은 독립적으로 17개 내지 26개의 뉴클레오타이드 길이이다. 몇몇 실시형태에서, 센스 및 안티센스 가닥은 19개 내지 26개의 뉴클레오타이드 길이이다. 몇몇 실시형태에서, 기재된 RNAi 물질 센스 및 안티센스 가닥은 독립적으로 17개, 18개, 19개, 20개, 21개, 22개, 23개, 24개, 25개 또는 26개의 뉴클레오타이드 길이이다. 센스 및 안티센스 가닥은 동일한 길이일 수 있거나, 상이한 길이일 수 있다. 몇몇 실시형태에서, 센스 가닥 및 안티센스 가닥은 각각 26개의 뉴클레오타이드 길이이다. 몇몇 실시형태에서, 센스 가닥은 23개의 뉴클레오타이드 길이이고, 안티센스 가닥은 21개의 뉴클레오타이드 길이이다. 몇몇 실시형태에서, 센스 가닥은 22개의 뉴클레오타이드 길이이고, 안티센스 가닥은 21개의 뉴클레오타이드 길이이다. 몇몇 실시형태에서, 센스 가닥은 21개의 뉴클레오타이드 길이이고, 안티센스 가닥은 21개의 뉴클레오타이드 길이이다. 몇몇 실시형태에서, 센스 가닥은 19개의 뉴클레오타이드 길이이고, 안티센스 가닥은 21개의 뉴클레오타이드 길이이다.
센스 가닥 및/또는 안티센스 가닥은 임의로 및 독립적으로 코어 서열의 3' 말단, 5' 말단, 또는 3' 및 5' 말단 둘 다에서 추가 1개, 2개, 3개, 4개, 5개 또는 6개의 뉴클레오타이드(연장)를 함유할 수 있다. 존재하는 경우, 안티센스 가닥 추가 뉴클레오타이드는 LPA mRNA에서의 상응하는 서열에 상보성이거나 아닐 수 있다. 존재하는 경우, 센스 가닥 추가 뉴클레오타이드는 LPA mRNA에서의 상응하는 서열에 동일하거나 동일하지 않을 수 있다. 존재하는 경우, 안티센스 가닥 추가 뉴클레오타이드는, 존재하는 경우, 상응하는 센스 가닥의 추가 뉴클레오타이드에 상보성이거나 아닐 수 있다.
본 명세서에 사용된 바와 같은, 연장은 센스 가닥 코어 서열 및/또는 안티센스 가닥 코어 서열의 5' 및/또는 3' 말단에서 1개, 2개, 3개, 4개, 5개 또는 6개의 뉴클레오타이드를 포함한다. 센스 가닥에서의 연장 뉴클레오타이드는 상응하는 안티센스 가닥에서 코어 서열 뉴클레오타이드 또는 연장 뉴클레오타이드 중 어느 하나인 뉴클레오타이드에 상보성이거나 아닐 수 있다. 반대로, 안티센스 가닥에서의 연장 뉴클레오타이드는 상응하는 센스 가닥에서 코어 서열 뉴클레오타이드 또는 연장 뉴클레오타이드 중 어느 하나인 뉴클레오타이드에 상보성이거나 아닐 수 있다. 몇몇 실시형태에서, RNAi 물질의 센스 가닥 및 안티센스 가닥은 둘 다 3' 및 5' 연장을 함유한다. 몇몇 실시형태에서, 하나의 가닥 염기의 하나 이상의 3' 연장 뉴클레오타이드는 다른 가닥의 하나 이상의 5' 연장 뉴클레오타이드와 쌍을 이룬다. 다른 실시형태에서, 하나의 가닥의 하나 이상의 3' 연장 뉴클레오타이드는 다른 가닥의 하나 이상의 5' 연장 뉴클레오타이드와 쌍을 이루지 않는다. 몇몇 실시형태에서, LPA RNAi 물질은 3' 연장을 가지는 안티센스 가닥 및 5' 연장을 가지는 센스 가닥을 가진다.
몇몇 실시형태에서, LPA RNAi 물질은 1개, 2개, 3개, 4개, 5개 또는 6개의 뉴클레오타이드 길이의 3' 연장을 가지는 안티센스 가닥을 포함한다. 다른 실시형태에서, LPA RNAi 물질은 1개, 2개 또는 3개의 뉴클레오타이드 길이의 3' 연장을 가지는 안티센스 가닥을 포함한다. 몇몇 실시형태에서, 하나 이상의 안티센스 가닥 연장 뉴클레오타이드는 우라실 또는 타이미딘 뉴클레오타이드 또는 상응하는 LPA mRNA 서열에 상보성인 뉴클레오타이드를 포함한다. 몇몇 실시형태에서, 3' 안티센스 가닥 연장은 Ab, AbAb, AUA, UGCUU, CUG, UG, UGCC, CUGCC, CGU, CUU, UGCCUA, CUGCCU, UGCCU, UGAUU, GCCUAU, T, TT(각각 5'에서 3'로 기재됨)를 포함하거나 이들로 이루어지지만, 이들로 제한되지는 않는다.
몇몇 실시형태에서, LPA RNAi 물질은 1개, 2개, 3개, 4개 또는 5개의 뉴클레오타이드 길이의 5' 연장을 가지는 안티센스 가닥을 포함한다. 다른 실시형태에서, LPA RNAi 물질은 1개 또는 2개의 뉴클레오타이드 길이의 5' 연장을 가지는 안티센스 가닥을 포함한다. 몇몇 실시형태에서, 하나 이상의 안티센스 가닥 연장 뉴클레오타이드는 우라실 또는 타이미딘 뉴클레오타이드 또는 상응하는 LPA mRNA 서열에 상보성인 뉴클레오타이드를 포함한다. 몇몇 실시형태에서, 5' 안티센스 가닥 연장은 UA, TU, U, T, CUC(각각 5'에서 3'로 기재됨)를 포함하거나 이들로 이루어지지만, 이들로 제한되지는 않는다. 안티센스 가닥은, 존재하는 경우, 기재된 임의의 5' 안티센스 가닥 연장과 조합되어 상기 기재된 임의의 3' 연장을 가질 수 있다.
몇몇 실시형태에서, LPA RNAi 물질은 1개, 2개, 3개, 4개 또는 5개의 뉴클레오타이드 길이의 3' 연장을 가지는 센스 가닥을 포함한다. 몇몇 실시형태에서, 하나 이상의 센스 가닥 연장 뉴클레오타이드는 아데노신, 우라실, 또는 타이미딘 뉴클레오타이드, AT 다이뉴클레오타이드, 또는 LPA mRNA 서열에서의 뉴클레오타이드에 상응하는 뉴클레오타이드를 포함한다. 몇몇 실시형태에서, 3' 센스 가닥 연장은 T, UUAb, UAb, Ab, UT, TT, UUT, TTT 또는 TTTT(각각 5'에서 3'로 기재됨)를 포함하거나 이들로 이루어지지만, 이들로 제한되지는 않는다.
몇몇 실시형태에서, LPA RNAi 물질은 1개, 2개, 3개, 4개, 5개 또는 6개의 뉴클레오타이드 길이의 5' 연장을 가지는 센스 가닥을 포함한다. 몇몇 실시형태에서, 하나 이상의 센스 가닥 연장 뉴클레오타이드는 우라실 또는 아데노신 뉴클레오타이드 또는 LPA mRNA 서열에서의 뉴클레오타이드에 상응하는 뉴클레오타이드를 포함한다. 몇몇 실시형태에서, 센스 가닥 5' 연장은 CA, AUAGGC, AUAGG, AUAG, AUA, A, AA, AC, GCA, GGCA, GGC, UAUCA, UAUC, Ab, UCA, UAU(각각 5'에서 3'로 기재됨)일 수 있지만, 이들로 제한되지는 않는다. 센스 가닥은 3' 연장 및/또는 5' 연장을 가질 수 있다.
LPA RNAi 물질을 형성하는 데 사용되는 뉴클레오타이드 서열의 예는 표 1, 표 2A, 표 2B, 표 3A 및 표 3B에 제공된다. 본 명세서에 사용된 바와 같은, 용어 "서열" 또는 "뉴클레오타이드 서열"은 표준 뉴클레오타이드 명명법 및 본 명세서에 기재된 변형된 뉴클레오타이드에 대한 키를 이용하여 철자의 연속에 의해 기재된, 변형되든 또는 변형되지 않든, 핵염기, 뉴클레오타이드, 및/또는 뉴클레오사이드의 연속 또는 순서를 의미한다.
RNAi 물질은 짧은 간섭 RNA(siRNA), 이중 가닥 RNA(dsRNA), 마이크로 RNA(miRNA), 짧은 헤어핀 RNA(shRNA) 및 다이서(dicer) 기질(예를 들어, 미국 특허 제8084599호, 제8349809호 및 제8513207호)를 포함하지만, 이들로 제한되지는 않는다.
비변형된 LPA RNAi 물질 센스 가닥 및 안티센스 가닥 서열은 표 1에 제공된다. LPA RNAi 물질을 형성하는 데 있어서, 표 1에 기재된 각각의 서열에서의 각각의 뉴클레오타이드는 변형된 뉴클레오타이드일 수 있다.
본 명세서에 기재된 LPA RNAi 물질은 안티센스 가닥을 센스 가닥에 의해 어닐링함으로써 형성된다. 표 1 또는 표 2B에 기재된 서열을 함유하는 센스 가닥은 표 1 또는 표 2A에 기재된 서열을 함유하는 임의의 안티센스 가닥에 혼성화될 수 있고, 단 2개의 서열은 인접한 16개, 17개, 18개, 19개, 20개 또는 21개의 뉴클레오타이드 서열에 대해 적어도 90% 상보성의 영역을 가진다.
몇몇 실시형태에서, LPA RNAi 물질 안티센스 가닥은 표 1에서의 임의의 서열의 뉴클레오타이드 서열을 포함한다. 몇몇 실시형태에서, LPA RNAi 물질 안티센스 가닥은 표 1에서의 임의의 서열의 1-17번, 2-17번, 1-18번, 2-18번, 1-19번, 2-19번, 1-20번, 2-20번, 1-21번, 2-21번, 1-22번, 2-22번, 1-23번, 2-23번, 1-24번, 2-24번, 1-25번, 2-25번, 1-26번 또는 2-26번 뉴클레오타이드의 서열을 포함한다. 몇몇 실시형태에서, LPA RNAi 물질 센스 가닥은 표 1에서의 임의의 서열의 뉴클레오타이드 서열을 포함한다. 몇몇 실시형태에서, LPA RNAi 물질 센스 가닥은 표 1에서의 임의의 서열의 1-17번, 2-17번, 1-18번, 2-18번, 1-19번, 2-19번, 1-20번, 2-20번, 1-21번, 2-21번, 1-22번, 2-22번, 1-23번, 2-23번, 1-24번, 2-24번, 1-25번, 2-25번, 1-26번 또는 2-26번 뉴클레오타이드의 서열을 포함한다.
몇몇 실시형태에서, 본 명세서에 기재된 RNAi 물질의 센스 및 안티센스 가닥은 동일한 수의 뉴클레오타이드를 함유한다. 몇몇 실시형태에서, 본 명세서에 기재된 RNAi 물질의 센스 및 안티센스 가닥은 상이한 수의 뉴클레오타이드를 함유한다. 몇몇 실시형태에서, RNAi 물질의 센스 가닥 5' 말단 및 안티센스 가닥 3' 말단은 무딘 말단을 형성한다. 몇몇 실시형태에서, RNAi 물질의 센스 가닥 3' 말단 및 안티센스 가닥 5' 말단은 무딘 말단을 형성한다. 몇몇 실시형태에서, RNAi 물질의 말단 둘 다는 무딘 말단을 형성한다. 몇몇 실시형태에서, RNAi 물질의 말단 중 어느 것도 무딘 말단이 아니다. 본 명세서에 사용된 바와 같은, 무딘 말단은, 2개의 어닐링된 가닥의 말단 뉴클레오타이드가 상보성인(상보성 염기 쌍을 형성하는), 이중 가닥 RNAi 물질의 말단을 의미한다. 몇몇 실시형태에서, RNAi 물질의 센스 가닥 5' 말단 및 안티센스 가닥 3' 말단은 날카로운 말단을 형성한다. 몇몇 실시형태에서, RNAi 물질의 센스 가닥 3' 말단 및 안티센스 가닥 5' 말단은 날카로운 말단을 형성한다. 몇몇 실시형태에서, RNAi 물질의 말단 둘 다는 날카로운 말단을 형성한다. 몇몇 실시형태에서, RNAi 물질의 말단 중 어느 것도 날카로운 말단이 아니다. 본 명세서에 사용된 바와 같은, 날카로운 말단은, 2개의 어닐링된 가닥의 말단 뉴클레오타이드가 쌍을 형성하지만(즉, 오버행(overhang)을 형성하지 않음), 상보성이 아닌(즉, 비상보성 쌍을 형성함), 이중 가닥 RNAi 물질의 말단을 의미한다. 본 명세서에 사용된 바와 같은, 오버행은 이중 가닥 RNAi 물질의 하나의 가닥의 말단에서의 하나 이상의 쌍 짖지 않은 뉴클레오타이드의 스트레치이다. 쌍 짖지 않은 뉴클레오타이드는 센스 가닥 또는 안티센스 가닥에 있을 수 있어서, 3' 또는 5' 오버행을 생성한다. 몇몇 실시형태에서, RNAi 물질은 무딘 말단 및 날카로운 말단, 무딘 말단 및 5' 오버행 말단, 무딘 말단 및 3' 오버행 말단, 날카로운 말단 및 5' 오버행 말단, 날카로운 말단 및 3' 오버행 말단, 2개의 5' 오버행 말단, 2개의 3' 오버행 말단, 5' 오버행 말단 및 3' 오버행 말단, 2개의 날카로운 말단, 또는 2개의 무딘 말단을 함유한다.
뉴클레오타이드 염기(또는 핵염기)는 모든 핵산의 구성성분인 헤테로사이클릭 피리미딘 또는 퓨린 화합물이고, 아데닌(A), 구아닌(G), 시토신(C), 타이민(T) 및 우라실(U)을 포함한다. 본 명세서에 사용된 바와 같은, 용어 "뉴클레오타이드"는 변형된 뉴클레오타이드 또는 뉴클레오타이드 모방체, 비염기성 부위(Ab 또는 X), 또는 대리 대체 모이어티를 포함할 수 있다.
몇몇 실시형태에서, LPA RNAi 물질은 염, 혼합 염 또는 유리 산으로서 제조되거나 제공된다.
변형된 뉴클레오타이드
몇몇 실시형태에서, LPA RNAi 물질은 하나 이상의 변형된 뉴클레오타이드를 함유한다. 본 명세서에 사용된 바대로, "변형된 뉴클레오타이드"는 리보뉴클레오타이드(2'-하이드록실 뉴클레오타이드) 이외의 뉴클레오타이드이다. 몇몇 실시형태에서, 적어도 50%, 적어도 60%, 적어도 70%, 적어도 80%, 적어도 90%, 적어도 95%, 또는 100%의 뉴클레오타이드는 변형된다. 변형된 뉴클레오타이드는 데옥시뉴클레오타이드, 뉴클레오타이드 모방체, 비염기성 뉴클레오타이드(X, Ab로서 본 명세서에서 표시됨), 2' 변형된 뉴클레오타이드, 3' 내지 3' 연결(인버티드) 뉴클레오타이드(invdN, invN, invn, invX, invAb로서 본 명세서에서 표시됨), 비천연 염기 포함 뉴클레오타이드, 브릿징된 뉴클레오타이드, 펩타이드 핵산(PNA), 2',3'-세코 뉴클레오타이드 모방체(잠기지 않은 핵염기 유사체, NUNA 또는 NUNA로서 본 명세서에서 표시됨), 잠긴 뉴클레오타이드(NLNA 또는 NLNA로서 본 명세서에서 표시됨), 3'-O-메톡시(2' 뉴클레오사이드간 연결된) 뉴클레오타이드(3'-OMen으로서 본 명세서에서 표시됨), 2'-F-아라비노 뉴클레오타이드(NfANA 또는 NfANA로서 본 명세서에서 표시됨), 5'-Me,2'-플루오로 뉴클레오타이드(5Me-Nf로서 본 명세서에서 표시됨), 모르폴리노 뉴클레오타이드, 비닐 포스포네이트 데옥시리보뉴클레오타이드(vpdN으로서 본 명세서에서 표시됨), 비닐 포스포네이트 함유 뉴클레오타이드 및 사이클로프로필 포스포네이트 함유 뉴클레오타이드(cPrpN)를 포함하지만, 이들로 제한되지는 않는다. 2' 변형된 뉴클레오타이드(즉, 5원 당 고리의 2'번 위치에서의 하이드록실기 이외의 기를 가지는 뉴클레오타이드)는 2'-O-메틸 뉴클레오타이드(뉴클레오타이드 서열에서 소문자 'n'으로서 본 명세서에서 표시됨), 2'-데옥시-2'-플루오로 뉴클레오타이드(Nf로서 본 명세서에서 표시됨, 또한 2'-플루오로 뉴클레오타이드로서 본 명세서에서 표시됨), 2'-데옥시 뉴클레오타이드(dN으로서 본 명세서에서 표시됨), 2'-메톡시에틸(2'-O-2-메톡실에틸) 뉴클레오타이드(NM 또는 2'-MOE로서 본 명세서에서 표시됨), 2'-아미노 뉴클레오타이드 및 2'-알킬 뉴클레오타이드를 포함하지만, 이들로 제한되지는 않는다. 균일하게 변형된 소정의 화합물에서 모든 위치에 이것이 필요하지 않다. 반대로, 하나 초과의 변형이 단일 LPA RNAi 물질에서 또는 심지어 이의 단일 뉴클레오타이드에서 혼입될 수 있다. LPA RNAi 물질 센스 가닥 및 안티센스 가닥은 당해 분야에 공지된 방법에 의해 합성되고/되거나 변형될 수 있다. 하나의 뉴클레오타이드에서의 변형은 또 다른 뉴클레오타이드에서의 변형에 독립적이다.
변형된 뉴클레오타이드는 또한 변형된 핵염기를 가지는 뉴클레오타이드를 포함한다. 변형된 핵염기는 합성 및 천연 핵염기, 5-치환된 피리미딘, 6-아자피리미딘 및 N-2, N-6 및 O-6 치환된 퓨린, 예컨대 2-아미노프로필아데닌, 5-프로피닐우라실 및 5-프로피닐시토신, 5-메틸시토신(5-me-C), 5-하이드록시메틸 시토신, 잔틴, 하이포잔틴, 2-아미노아데닌, 아데닌 및 구아닌의 6-메틸 및 다른 알킬 유도체, 아데닌 및 구아닌의 2-프로필 및 다른 알킬 유도체, 2-티오우라실, 2-티오타이민 및 2-티오시토신, 5-할로우라실 및 시토신, 5-프로피닐 우라실 및 시토신, 6-아조 우라실, 시토신 및 타이민, 5-우라실(슈도우라실), 4-티오우라실, 8-할로, 8-아미노, 8-티올, 8-티오알킬, 8-하이드록실 및 다른 8-치환된 아데닌 및 구아닌, 5-할로 특히 5-브로모, 5-트라이플루오로메틸 및 다른 5-치환된 우라실 및 시토신, 7-메틸구아닌 및 7-메틸아데닌, 8-아자구아닌 및 8-아자아데닌, 7-데아자구아닌 및 7-데아자아데닌 및 3-데아자구아닌 및 3-데아자아데닌을 포함하지만, 이들로 제한되지는 않는다.
변형된 뉴클레오사이드간 연결
몇몇 실시형태에서, LPA RNAi 물질의 하나 이상의 뉴클레오타이드는 비표준 연결 또는 골격(즉 변형된 뉴클레오사이드간 연결 또는 변형된 골격)에 의해 연결된다. 몇몇 실시형태에서, 변형된 뉴클레오사이드간 연결은 비포스페이트 함유 공유 뉴클레오사이드간 연결이다. 변형된 뉴클레오사이드간 연결 또는 골격은 5'-포스포로티오에이트기(sN, sn, sNf 또는 sdN에서처럼 뉴클레오타이드 앞에 소문자 's'로서 본 명세서에서 표시됨), 키랄 포스포로티오에이트, 티오포스페이트, 포스포로다이티오에이트, 포스포트라이에스터, 아미노알킬-포스포트라이에스터, 메틸 및 다른 알킬 포스포네이트, 예컨대 3'-알킬렌 포스포네이트 및 키랄 포스포네이트, 포스피네이트, 포스포르아미데이트, 예컨대 3'-아미노 포스포르아미데이트 및 아미노알킬포스포르아미데이트, 티오노포스포르아미데이트, 티오노알킬-포스포네이트, 티오노알킬포스포트라이에스터, 모르폴리노 연결, 및 일반 3'-5' 연결을 가지는 보라노포스페이트, 이들의 2'-5' 연결된 유사체, 및 반전 극성을 가지는 것(여기서, 뉴클레오사이드 단위의 인접한 쌍은 3'-5' 내지 5'-3' 또는 2'-5' 내지 5'-2' 연결됨)을 포함하지만, 이들로 제한되지는 않는다. 다른 실시형태에서, 변형된 뉴클레오사이드간 연결 또는 골격은 인 원자가 결여된다. 인 원자가 결여된 변형된 뉴클레오사이드간 연결은 짧은 사슬 알킬 또는 사이클로알킬 당간 연결, 혼합된 이종원자 및 알킬 또는 사이클로알킬 당간 연결, 또는 하나 이상의 짧은 사슬 이종원자 또는 헤테로사이클 당간 연결을 포함하지만, 이들로 제한되지는 않는다. 몇몇 실시형태에서, 변형된 뉴클레오사이드간 골격은 실록산 골격, 설파이드, 설폭사이드 및 설폰 골격; 폼아세틸 및 티오폼아세틸 골격, 메틸렌 폼아세틸 및 티오폼아세틸 골격, 알켄 함유 골격, 설파메이트 골격, 메틸렌이미노 및 메틸렌하이드라지노 골격, 설포네이트 및 설폰아미드 골격, 아미드 골격; 및 혼합된 N, O, S, 및 CH2 성분 파트를 가지는 기타를 포함하지만, 이들로 제한되지는 않는다.
몇몇 실시형태에서, LPA RNAi 물질의 센스 가닥은 1개, 2개, 3개 또는 4개의 포스포로티오에이트 연결을 함유할 수 있고, LPA RNAi 물질의 안티센스 가닥은 1개, 2개, 3개 또는 4개의 포스포로티오에이트 연결을 함유할 수 있거나, 센스 가닥 및 안티센스 가닥 둘 다는 독립적으로 1개, 2개, 3개 또는 4개의 포스포로티오에이트 연결을 함유할 수 있다.
몇몇 실시형태에서, LPA RNAi 물질 센스 가닥은 2개의 포스포로티오에이트 뉴클레오사이드간 연결을 함유한다. 몇몇 실시형태에서, 2개의 포스포로티오에이트 뉴클레오사이드간 연결은 센스 가닥의 3' 말단으로부터 1-3번 위치에서의 뉴클레오타이드 사이이다. 몇몇 실시형태에서, 2개의 포스포로티오에이트 뉴클레오사이드간 연결은 센스 가닥의 5' 말단으로부터 1-3번, 2-4번, 3-5번, 4-6번, 4-5번 또는 6-8번 위치에서의 뉴클레오타이드 사이이다. 몇몇 실시형태에서, LPA RNAi 물질 안티센스 가닥은 4개의 포스포로티오에이트 뉴클레오사이드간 연결을 함유한다. 몇몇 실시형태에서, 4개의 포스포로티오에이트 뉴클레오사이드간 연결은 센스 가닥의 5' 말단으로부터의 1-3번 위치에서의 뉴클레오타이드 사이 및 5' 말단으로부터의 19-21번, 20-22번, 21-23번, 22-24번, 23-25번 또는 24-26번 위치에서의 뉴클레오타이드 사이이다. 몇몇 실시형태에서, LPA RNAi 물질은 센스 가닥에서의 2개의 포스포로티오에이트 뉴클레오사이드간 연결 및 안티센스 가닥에서의 4개의 포스포로티오에이트 뉴클레오사이드간 연결을 함유한다.
몇몇 실시형태에서, LPA RNAi 물질은 하나 이상의 변형된 뉴클레오타이드 및 하나 이상의 변형된 뉴클레오사이드간 연결을 함유한다. 몇몇 실시형태에서, 2'-변형된 뉴클레오타이드는 변형된 뉴클레오사이드간 연결과 조합된다.
변형된 뉴클레오타이드를 가지는 LPA RNAi 물질
변형된 뉴클레오타이드를 함유하는 안티센스 가닥의 예는 표 2A에 제공된다. 변형된 뉴클레오타이드를 함유하는 센스 가닥의 예는 표 2B에 제공된다. 표 2A 및 2B에서, 하기 주석은 변형된 뉴클레오타이드를 표시하도록 사용된다:
N =
2'-OH (비변형된) 리보뉴클레오타이드(f 또는 d 표시가 없는 대문자)
n =
2'-OMe 변형된 뉴클레오타이드
Nf =
2'-플루오로 변형된 뉴클레오타이드
dN =
2'-데옥시 뉴클레오타이드
NUNA =
2',3'-세코 뉴클레오타이드 모방체(잠기지 않은 핵염기 유사체)
NLNA =
잠긴 뉴클레오타이드
NfANA =
2'-F-아라비노 뉴클레오타이드
NM =
2'-메톡시에틸 뉴클레오타이드
Ab =
비염기성 리보스
(invdN) =
인버티드 데옥시리보뉴클레오타이드(3'-3' 연결된 뉴클레오타이드)
(invAb) =
인버티드 비염기성 뉴클레오타이드
(invn) =
인버티드 2'-OMe 뉴클레오타이드
s =
포스포로티오에이트 연결된 뉴클레오타이드
p =
포스페이트
vpdN =
비닐 포스포네이트 데옥시리보뉴클레오타이드
(3'OMen) =
3'-OMe 뉴클레오타이드
(5Me-Nf) =
5'-Me, 2'-플루오로 뉴클레오타이드
cPrp =
사이클로프로필 포스포네이트
epTcPr =
표 4 참조
epTM =
표 4 참조
또한, 하기 표적화기 및 연결기는 표 2A 및 2B에 기재되어 있다: (Alk-PEG5-C6), (C11-PEG3-NAG3), (C12), (C6-PEG4-NAG3), (C6-SS-Alk-Me), (Chol-TEG), (Dy540), (NAG13), (NAG18), (NAG24), (NAG25), (NAG26), (NAG27), (NAG28), (NAG29), (NAG30), (NAG31), (NAG32), (NAG33), (NAG34), (NAG35), (NAG36), (NAG37), (NAG4), (PAZ), (Sp18), (Steryl), (Alk-SMPT-C6). 각각의 센스 가닥 및/또는 안티센스 가닥은 임의의 상기 표시된 표적화기 또는 연결기, 및 서열의 5' 및 또는 3' 말단에 접합된 다른 표적화 또는 연결기를 가질 수 있다. 이 기에 대한 화학 구조는 표 4에 제공된다.
표 2B에 기재된 서열을 함유하는 센스 가닥은 표 2A에 기재된 서열을 함유하는 임의의 안티센스 가닥에 혼성화될 수 있고, 단 2개의 서열은 인접한 16개, 17개, 18개, 19개, 20개 또는 21개의 뉴클레오타이드 서열에 걸쳐 적어도 90% 상보성의 영역을 가진다. 대표적인 LPA RNAi 물질은 표 3A 및 3B에 기재된 듀플렉스 번호로 표시된다.
몇몇 실시형태에서, LPA RNAi 물질은 본 명세서에 제시된 임의의 듀플렉스 번호를 포함한다. 몇몇 실시형태에서, LPA RNAi 물질은 본 명세서에 제시된 임의의 듀플렉스 번호로 이루어진다. 몇몇 실시형태에서, LPA RNAi 물질은 본 명세서에 제시된 임의의 듀플렉스 번호의 센스 가닥 및 안티센스 가닥 뉴클레오타이드 서열을 포함한다. 몇몇 실시형태에서, LPA RNAi 물질은 본 명세서에 제시된 임의의 듀플렉스 번호의 센스 가닥 및 안티센스 가닥 뉴클레오타이드 서열 및 표적화기 및/또는 연결기를 포함하고, 표적화기 및/또는 연결기는 센스 가닥 또는 안티센스 가닥에 공유로 연결(즉, 접합)된다. 몇몇 실시형태에서, LPA RNAi 물질은 본 명세서에 제시된 임의의 듀플렉스 번호의 센스 가닥 및 안티센스 가닥 변형된 뉴클레오타이드 서열을 포함한다. 몇몇 실시형태에서, LPA RNAi 물질은 본 명세서에 제시된 임의의 듀플렉스 번호의 센스 가닥 및 안티센스 가닥 변형된 뉴클레오타이드 서열 및 표적화기 및/또는 연결기를 포함하고, 표적화기 및/또는 연결기는 센스 가닥 또는 안티센스 가닥에 공유로 연결된다.
몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 1242(TCGUAUAACAAUAAGGGGC)의 뉴클레오타이드 서열을 포함하는 안티센스 가닥을 포함한다. 몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 1244(UCGUAUAACAAUAAGGGG)의 뉴클레오타이드 서열을 포함하는 안티센스 가닥을 포함한다. 몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 1246(UCGUAUAACAAUAAGGG)의 뉴클레오타이드 서열을 포함하는 안티센스 가닥을 포함한다. 몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 1248(TGAGAAUGAGCCUCGAUAA)의 뉴클레오타이드 서열을 포함하는 안티센스 가닥을 포함한다. 몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 1250(UGAGAAUGAGCCUCGAUA)의 뉴클레오타이드 서열을 포함하는 안티센스 가닥을 포함한다. 몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 1252(UGAGAAUGAGCCUCGAU)의 뉴클레오타이드 서열을 포함하는 안티센스 가닥을 포함한다. 몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 1254(UGUAUAACAAUAAGGGG)의 뉴클레오타이드 서열을 포함하는 안티센스 가닥을 포함한다. 몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 1280(CGUAUAACAAUAAGGGGC)의 뉴클레오타이드 서열을 포함하는 안티센스 가닥을 포함한다. 몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 1281(GAGAAUGAGCCUCGAUAA)의 뉴클레오타이드 서열을 포함하는 안티센스 가닥을 포함한다. 몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 1282(UCGUAUAACAAUAAGGGGC)의 뉴클레오타이드 서열을 포함하는 안티센스 가닥을 포함한다. 몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 1283(UGAGAAUGAGCCUCGAUAA)의 뉴클레오타이드 서열을 포함하는 안티센스 가닥을 포함한다. 몇몇 실시형태에서, 하나 이상의 뉴클레오타이드는 변형된다.
몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 1243(GCCCCUUAUUGUUAUACGA)의 뉴클레오타이드 서열을 포함하는 센스 가닥을 포함한다. 몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 1245(CCCCUUAUUGUUAUACGA)의 뉴클레오타이드 서열을 포함하는 센스 가닥을 포함한다. 몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 1247(CCCUUAUUGUUAUACGA)의 뉴클레오타이드 서열을 포함하는 센스 가닥을 포함한다. 몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 1249(UUAUCGAGGCUCAUUCUCA)의 뉴클레오타이드 서열을 포함하는 센스 가닥을 포함한다. 몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 1251(UAUCGAGGCUCAUUCUCA)의 뉴클레오타이드 서열을 포함하는 센스 가닥을 포함한다. 몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 1253(AUCGAGGCUCAUUCUCA)의 뉴클레오타이드 서열을 포함하는 센스 가닥을 포함한다. 몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 1255(CCCCUUAUUGUUAUACA)의 뉴클레오타이드 서열을 포함하는 센스 가닥을 포함한다. 몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 1284(GCCCCUUAUUGUUAUACG)의 뉴클레오타이드 서열을 포함하는 센스 가닥을 포함한다. 몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 1285(UUAUCGAGGCUCAUUCUC)의 뉴클레오타이드 서열을 포함하는 센스 가닥을 포함한다. 몇몇 실시형태에서, 하나 이상의 뉴클레오타이드는 변형된다.
몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 1242의 뉴클레오타이드 서열을 포함하는 안티센스 가닥 및 서열 번호 1243의 뉴클레오타이드 서열을 포함하는 센스 가닥을 포함한다. 몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 1244의 뉴클레오타이드 서열을 포함하는 안티센스 가닥 및 서열 번호 1245의 뉴클레오타이드 서열을 포함하는 센스 가닥을 포함한다. 몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 1246의 뉴클레오타이드 서열을 포함하는 안티센스 가닥 및 서열 번호 1247의 뉴클레오타이드 서열을 포함하는 센스 가닥을 포함한다. 몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 1248의 뉴클레오타이드 서열을 포함하는 안티센스 가닥 및 서열 번호 1249의 뉴클레오타이드 서열을 포함하는 센스 가닥을 포함한다. 몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 1250의 뉴클레오타이드 서열을 포함하는 안티센스 가닥 및 서열 번호 1251의 뉴클레오타이드 서열을 포함하는 센스 가닥을 포함한다. 몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 1252의 뉴클레오타이드 서열을 포함하는 안티센스 가닥 및 서열 번호 1253의 뉴클레오타이드 서열을 포함하는 센스 가닥을 포함한다. 몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 1254의 뉴클레오타이드 서열을 포함하는 안티센스 가닥 및 서열 번호 1255의 뉴클레오타이드 서열을 포함하는 센스 가닥을 포함한다. 몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 1280의 뉴클레오타이드 서열을 포함하는 안티센스 가닥 및 서열 번호 1284의 뉴클레오타이드 서열을 포함하는 센스 가닥을 포함한다. 몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 1281의 뉴클레오타이드 서열을 포함하는 안티센스 가닥 및 서열 번호 1285의 뉴클레오타이드 서열을 포함하는 센스 가닥을 포함한다. 몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 1282의 뉴클레오타이드 서열을 포함하는 안티센스 가닥 및 서열 번호 1259의 뉴클레오타이드 서열을 포함하는 센스 가닥을 포함한다. 몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 1283의 뉴클레오타이드 서열을 포함하는 안티센스 가닥 및 서열 번호 1249의 뉴클레오타이드 서열을 포함하는 센스 가닥을 포함한다. 몇몇 실시형태에서, 하나 이상의 뉴클레오타이드는 변형된다.
몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 156, 164 또는 188의 뉴클레오타이드 서열을 포함하는 안티센스 가닥을 포함한다. 몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 310, 357, 384 또는 376의 뉴클레오타이드 서열을 포함하는 센스 가닥을 포함한다. 몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 156/310, 서열 번호 164/357, 서열 번호 188/384, 서열 번호 164/376 또는 서열 번호 164/384의 뉴클레오타이드 서열을 포함하는 안티센스 가닥 및 센스 가닥을 포함한다. 몇몇 실시형태에서, 하나 이상의 뉴클레오타이드는 변형된다.
몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 637, 709, 790, 787 또는 788의 뉴클레오타이드 서열을 포함하는 안티센스 가닥을 포함한다. 몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 1132, 1135, 1189, 1191 또는 1186의 뉴클레오타이드 서열을 포함하는 센스 가닥을 포함한다. 몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 637/1132, 서열 번호 709/1135, 서열 번호 790/1189, 서열 번호 787/1191 또는 서열 번호 788/1186의 뉴클레오타이드 서열을 포함하는 안티센스 가닥 및 센스 가닥을 포함한다.
몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 637, 709, 790, 787 또는 788을 포함한다. 몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 1132, 1135, 1189, 1191 또는 1186을 포함한다. 몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 637/1132, 서열 번호 709/1135, 서열 번호 790/1189, 서열 번호 787/1191 또는 서열 번호 788/1186을 포함한다.
몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 637, 709, 790, 787 또는 788로 이루어진다. 몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 1132, 1135, 1189, 1191 또는 1186으로 이루어진다. 몇몇 실시형태에서, LPA RNAi 물질은 서열 번호 637/1132, 서열 번호 709/1135, 서열 번호 790/1189, 서열 번호 787/1191, 또는 서열 번호 788/1186으로 이루어진다.
몇몇 실시형태에서, LPA RNAi 물질은 표 3A 또는 표 3B의 임의의 안티센스 가닥/센스 가닥 듀플렉스의 뉴클레오타이드 서열을 가지는 안티센스 가닥 및 센스 가닥을 포함한다.
몇몇 실시형태에서, LPA RNAi 물질은 표 3A 또는 표 3B의 임의의 안티센스 가닥/센스 가닥 듀플렉스의 뉴클레오타이드 서열을 가지는 안티센스 가닥 및 센스 가닥을 포함하고, 아시알로당단백질 수용체 리간드 표적화기를 추가로 포함한다.
몇몇 실시형태에서, LPA RNAi 물질은 표 3A 또는 표 3B의 임의의 안티센스 가닥/센스 가닥 듀플렉스의 뉴클레오타이드 서열을 가지는 안티센스 가닥 및 센스 가닥을 포함하고, (C11-PEG3-NAG3), (C11-PEG3-NAG3), (C6-PEG4-NAG3), (NAG 3), (NAG4), (NAG3-AA2), (NAG3-Palm), (NAG13), (NAG18), (NAG24), (NAG25), (NAG25)s, (NAG26), (NAG27), (NAG28), (NAG29), (NAG30), (NAG30)s, (NAG31), (NAG13), (NAG31s), (NAG32), (NAG33), (NAG34), (NAG35), (NAG36) 및 (NAG37)로 이루어진 군으로부터 선택된 표적화기를 추가로 포함한다.
몇몇 실시형태에서, LPA RNAi 물질은 표 3A 또는 표 3B의 임의의 안티센스 가닥/센스 가닥 듀플렉스의 변형된 뉴클레오타이드 서열을 가지는 안티센스 가닥 및 센스 가닥을 포함한다.
몇몇 실시형태에서, LPA RNAi 물질은 표 3A 또는 표 3B의 임의의 안티센스 가닥/센스 가닥 듀플렉스의 변형된 뉴클레오타이드 서열을 가지는 안티센스 가닥 및 센스 가닥을 포함하고, 아시알로당단백질 수용체 리간드 표적화기를 추가로 포함한다.
몇몇 실시형태에서, LPA RNAi 물질은 표 3A 또는 표 3B의 임의의 안티센스 가닥/센스 가닥 듀플렉스의 변형된 뉴클레오타이드 서열을 가지는 안티센스 가닥 및 센스 가닥을 포함하고, (C11-PEG3-NAG3), (C11-PEG3-NAG3), (C6-PEG4-NAG3), (NAG 3), (NAG4), (NAG3-AA2), (NAG3-Palm), (NAG13), (NAG18), (NAG24), (NAG25), (NAG25)s, (NAG26), (NAG27), (NAG28), (NAG29), (NAG30), (NAG30)s, (NAG31), (NAG13), (NAG31s), (NAG32), (NAG33), (NAG34), (NAG35), (NAG36) 및 (NAG37)로 이루어진 군으로부터 선택된 표적화기를 추가로 포함한다.
몇몇 실시형태에서, LPA RNAi 물질은 표 3A 또는 표 3B의 임의의 듀플렉스를 포함한다.
몇몇 실시형태에서, LPA RNAi 물질은 표 3A 또는 표 3B의 임의의 듀플렉스로 이루어진다.
몇몇 실시형태에서, LPA RNAi 물질은 뉴클레오타이드 서열 AD03460, AD03536, AD03581, AD03583, AD3847 또는 AD04110을 가지는 안티센스 가닥 및 센스 가닥을 포함한다.
몇몇 실시형태에서, LPA RNAi 물질은 뉴클레오타이드 서열 AD03460, AD03536, AD03581, AD03583, AD3847 또는 AD04110을 가지는 안티센스 가닥 및 센스 가닥을 포함하고, 아시알로당단백질 수용체 리간드 표적화기를 추가로 포함한다.
몇몇 실시형태에서, LPA RNAi 물질은 뉴클레오타이드 서열 AD03460, AD03536, AD03581, AD03583, AD3847 또는 AD04110을 가지는 안티센스 가닥 및 센스 가닥을 포함하고, (C11-PEG3-NAG3), (C11-PEG3-NAG3), (C6-PEG4-NAG3), (NAG 3), (NAG4), (NAG3-AA2), (NAG3-Palm), (NAG13), (NAG18), (NAG24), (NAG25), (NAG25)s, (NAG26), (NAG27), (NAG28), (NAG29), (NAG30), (NAG30)s, (NAG31), (NAG13), (NAG31s), (NAG32), (NAG33), (NAG34), (NAG35), (NAG36) 및 (NAG37)로 이루어진 군으로부터 선택된 표적화기를 추가로 포함한다.
몇몇 실시형태에서, LPA RNAi 물질은 변형된 뉴클레오타이드 서열 AD03460, AD03536, AD03581, AD03583, AD3847 또는 AD04110을 가지는 안티센스 가닥 및 센스 가닥을 포함한다.
몇몇 실시형태에서, LPA RNAi 물질은 변형된 뉴클레오타이드 서열 AD03460, AD03536, AD03581, AD03583, AD3847 또는 AD04110을 가지는 안티센스 가닥 및 센스 가닥을 포함하고, 아시알로당단백질 수용체 리간드 표적화기를 추가로 포함한다.
몇몇 실시형태에서, LPA RNAi 물질은 변형된 뉴클레오타이드 서열 AD03460, AD03536, AD03581, AD03583, AD3847 또는 AD04110을 가지는 안티센스 가닥 및 센스 가닥을 포함하고, (C11-PEG3-NAG3), (C11-PEG3-NAG3), (C6-PEG4-NAG3), (NAG3), (NAG4), (NAG3-AA2), (NAG3-Palm), (NAG13), (NAG18), (NAG24), (NAG25), (NAG25)s, (NAG26), (NAG27), (NAG28), (NAG29), (NAG30), (NAG30)s, (NAG31), (NAG13), (NAG31s), (NAG32), (NAG33), (NAG34), (NAG35), (NAG36) 및 (NAG37)로 이루어진 군으로부터 선택된 표적화기를 추가로 포함한다.
몇몇 실시형태에서, LPA RNAi 물질은 AD03460, AD03536, AD03581, AD03583, AD3847 또는 AD04110을 포함한다.
몇몇 실시형태에서, LPA RNAi 물질은 AD03460, AD03536, AD03581, AD03583, AD3847 또는 AD04110으로 이루어진다.
비뉴클레오타이드기
몇몇 실시형태에서, LPA RNAi 물질은 표적화기, 연결기, 전달 중합체, 또는 전달 비히클(이들로 제한되지는 않음)을 포함하는 하나 이상의 비뉴클레오타이드기를 함유하거나 이에 접합된다. 비뉴클레오타이드기는 RNAi 물질의 표적화, 전달 또는 부착을 증대시킬 수 있다. 표적화기 및 연결기의 예는 표 4에 제공된다. 비뉴클레오타이드기는 센스 가닥 및/또는 안티센스 가닥 중 어느 하나의 3' 및/또는 5' 말단에 공유로 연결될 수 있다. 몇몇 실시형태에서, LPA RNAi 물질은 센스 가닥의 3' 및/또는 5' 말단에 연결된 비뉴클레오타이드기를 함유한다. 몇몇 실시형태에서, 비뉴클레오타이드기는 LPA RNAi 물질 센스 가닥의 5' 말단에 연결된다. 비뉴클레오타이드기는 RNAi 물질에 직접적으로 또는 간접적으로 링커/연결기를 통해 연결될 수 있다. 몇몇 실시형태에서, 비뉴클레오타이드기는 불안정한, 절단 가능한 또는 가역적 결합 또는 링커를 통해 RNAi 물질에 연결된다.
몇몇 실시형태에서, 비뉴클레오타이드기는 세포 또는 조직 특이적 분포 및 접합체의 세포 특이적 흡수를 개선하도록 RNAi 물질 또는 이것이 부착된 접합체의 약동학적 또는 생물분포 특성을 증대시킨다. 몇몇 실시형태에서, 비뉴클레오타이드기는 RNAi 물질의 내포작용을 증대시킨다.
표적화기
표적화기는 1가, 2가, 3가, 4가 또는 더 고차의 원자가일 수 있다. 대표적인 표적화기는, 제한 없이, 세포 표면 분자에 대한 친화도를 가지는 화합물, 세포 수용체 리간드, 합텐, 항체, 단일클론 항체, 항체 단편, 및 세포 표면 분자에 대한 친화도를 가지는 항체 모방체를 포함한다. 몇몇 실시형태에서, 표적화기는 링커, 예컨대 PEG 링커 또는 1개, 2개 또는 3개의 비염기성 및/또는 리비톨기를 사용하여 RNAi 물질에 연결된다. 몇몇 실시형태에서, 표적화기는 갈락토스 클러스터를 포함한다.
5'-말단에서 반응성 기, 예컨대 아민기를 가지는, 본 명세서에 기재된 LPA RNAi 물질은 합성될 수 있다. 반응성 기는 후속하여 당해 분야에서 통상적인 방법을 이용하여 표적화 모이어티에 부착하도록 사용될 수 있다.
몇몇 실시형태에서, 표적화기는 아시알로당단백질 수용체 리간드를 포함한다. 몇몇 실시형태에서, 아시알로당단백질 수용체 리간드는 하나 이상의 갈락토스 유도체 또는 갈락토스 클러스터를 포함하거나, 이것으로 이루어진다. 본 명세서에 사용된 바대로, 용어 갈락토스 유도체는 갈락토스와 동일하거나 이보다 큰 아시알로당단백질 수용체에 대한 친화도를 가지는 갈락토스 및 갈락토스의 유도체 둘 다를 포함한다. 갈락토스 유도체는 갈락토스, 갈락토스아민, N-폼일갈락토스아민, N-아세틸-갈락토스아민, N-프로피오닐-갈락토스아민, N-n-뷰타노일-갈락토스아민 및 N-아이소-뷰타노일갈락토스-아민을 포함하지만, 이들로 제한되지는 않는다(예를 들어, 문헌[Iobst, S.T. and Drickamer, K. J.B.C . 1996, 271, 6686] 참조). 간에 대한 올리고뉴클레오타이드 및 다른 분자의 생체내 표적화에 유용한 갈락토스 유도체 및 갈락토스 클러스터는 당해 분야에 공지되어 있다(예를 들어, 문헌[Baenziger and Fiete, 1980, Cell, 22, 611-620; Connolly et al., 1982, J. Biol. Chem., 257, 939-945] 참조). 갈락토스 유도체는 간세포의 표면에서 발현된 아시알로당단백질 수용체(ASGPr)에 대한 이의 결합을 통해 생체내 간세포로 분자를 표적화하도록 사용된다. ASGPr(들)로의 ASGPr 리간드의 결합은 간세포에 대한 세포 특이적 표적화 및 간세포로의 분자의 내포작용을 촉진한다. 갈락토스 클러스터는 당해 분야에 공지된 방법을 이용하여 RNAi 폴리뉴클레오타이드의 3' 또는 5' 말단에 부착될 수 있다.
본 명세서에 사용된 바대로, 갈락토스 클러스터는 2개 내지 4개의 말단 갈락토스 유도체를 가지는 분자를 포함한다. 말단 갈락토스 유도체는 이의 C-1 탄소를 통해 분자에 부착된다. 몇몇 실시형태에서, 갈락토스 클러스터는 갈락토스 유도체 삼합체, 트라이-안테너리(tri-antennary) 갈락토스 유도체 또는 3가 갈락토스 유도체이다. 몇몇 실시형태에서, 갈락토스 클러스터는 N-아세틸갈락토스아민(GalNAc)을 포함한다. 몇몇 실시형태에서, 갈락토스 클러스터는 3가 N-아세틸-갈락토스아민을 포함한다. 몇몇 실시형태에서, 갈락토스 클러스터는 갈락토스 유도체 사합체, 테트라-안테너리 갈락토스 유도체 또는 4가 갈락토스 유도체이다. 몇몇 실시형태에서, 갈락토스 클러스터는 4가 N-아세틸-갈락토스아민을 포함한다.
본 명세서에 사용된 바대로, 갈락토스 삼합체는 중앙 분지점에 각각 연결된 3개의 갈락토스 유도체를 함유한다. 본 명세서에 사용된 바대로, 갈락토스 유도체 사합체는 중앙 분지점에 각각 연결된 4개의 갈락토스 유도체를 함유한다. 갈락토스 유도체는 사카라이드의 C-1 탄소를 통해 중앙 분지점에 부착될 수 있다. 몇몇 실시형태에서, 갈락토스 유도체는 링커 또는 스페이서를 통해 분지점에 연결된다. 몇몇 실시형태에서, 링커 또는 스페이서는 가요성 친수성 스페이서, 예컨대 PEG 기이다(예를 들어, 문헌[미국 특허 제5885968호; Biessen et al. J. Med. Chem. 1995 Vol. 39 p. 1538-1546] 참조). 몇몇 실시형태에서, PEG 스페이서는 PEG3 스페이서이다. 분지점은 3개의 갈락토스 유도체의 부착을 허용하는 임의의 소분자일 수 있고, RNAi 물질에 대한 분지점의 부착을 추가로 허용한다. 분지점 기의 예는 다이라이신 또는 다이글루타메이트이다. RNAi 물질에 대한 분지점의 부착은 링커 또는 스페이서를 통해 발생할 수 있다. 몇몇 실시형태에서, 링커 또는 스페이서는 가요성 친수성 스페이서, 예컨대 PEG 스페이서(이들로 제한되지는 않음)를 포함한다. 몇몇 실시형태에서, PEG 스페이서는 PEG3 스페이서(3개의 에틸렌 단위)이다. 다른 실시형태에서, PEG 스페이서는 1개 내지 20개의 에틸렌 단위(PEG1 내지 PEG20)를 가진다. 몇몇 실시형태에서, 갈락토스 유도체는 N-아세틸갈락토스아민(GalNAc 또는 NAG)을 포함한다. 몇몇 실시형태에서, 갈락토스 클러스터는 갈락토스 유도체 사합체로 이루어지고, 이것은 예를 들어, N-아세틸-갈락토스아민 사합체일 수 있다.
몇몇 실시형태에서, 생체내 간 세포로 LPA RNAi 물질을 전달하기 위한 약제학적 조성물이 기재되어 있다. 이러한 약제학적 조성물은 예를 들어 갈락토스 클러스터에 접합된 LPA RNAi 물질을 포함할 수 있다. 몇몇 실시형태에서, 갈락토스 클러스터는 갈락토스 유도체 삼합체(예를 들어, N-아세틸-갈락토스아민 삼합체일 수 있음) 또는 갈락토스 유도체 사합체(이것은 예를 들어, N-아세틸-갈락토스아민 사합체일 수 있음)로 이루어진다.
표적화기는 (Chol-TEG), (TEG-Chol), (C11-PEG3-NAG3), (Cm-PEGn-NAG3), (Cx-PEGz-NAG3), (NAG 3), (NAG4), (NAG3-AA2), (NAG3-Palm), (NAG13), (NAG18), (NAG24), (NAG25), (NAG25)s, (NAG26), (NAG27), (NAG28), (NAG29), (NAG30), (NAG30)s, (NAG31), (NAG13), (NAG31s), (NAG32), (NAG33), (NAG34), (NAG35), (NAG36) 및 (NAG37)을 포함하지만, 이들로 제한되지는 않는다.
연결기
몇몇 실시형태에서, 연결기는 RNAi 물질에 접합된다. 연결기는 표적화기 기 또는 전달 중합체 또는 전달 비히클에 대한 상기 물질의 공유 연결을 촉진한다. 연결기는 RNAi 물질 센스 가닥 또는 안티센스 가닥의 3' 또는 5' 말단에 연결될 수 있다. 몇몇 실시형태에서, 연결기는 RNAi 물질 센스 가닥에 연결된다. 몇몇 실시형태에서, 연결기는 RNAi 물질 센스 가닥의 5' 또는 3' 말단에 접합된다. 몇몇 실시형태에서, 연결기는 RNAi 물질 센스 가닥의 5' 말단에 접합된다. 연결기의 예는 Alk-SMPT-C6, Alk-SS-C6, DBCO-TEG, Me-Alk-SS-C6, 및 C6-SS-Alk-Me, 반응성 기, 예컨대 1차 아민 및 알킨, 알킬기, 비염기성 리보스, 리비톨, 및/또는 PEG 기를 포함하지만, 이들로 제한되지는 않는다.
링커 또는 연결기는 하나 이상의 공유 결합을 통해 1개의 화학 기(예컨대 RNAi 물질) 또는 관심 있는 분절을 또 다른 화학 기(예컨대 표적화기 또는 전달 중합체) 또는 관심 있는 분절에 연결하는 2개의 원자 사이의 연결이다. 불안정한 연결은 불안정한 결합을 함유한다. 연결은 2개의 연결된 원자 사이의 거리를 증가시키는 스페이서를 임의로 포함할 수 있다. 스페이서는 추가로 연결에 가요성 및/또는 길이를 추가할 수 있다. 스페이서는 알킬기, 알켄일기, 알킨일기, 아릴기, 아르알킬기, 아르알켄일기 및 아르알킨일기를 포함할 수 있지만, 이들로 제한되지는 않고, 이들은 각각 하나 이상의 이종원자, 헤테로사이클, 아미노산, 뉴클레오타이드 및 사카라이드를 함유할 수 있다. 스페이서기는 당해 분야에 널리 공지되어 있고, 이전의 목록은 설명의 범위를 제한하도록 의도되지 않는다.
연결기는 알킬, PEG, (C6-PEGn-Alk), (Cn-SMPT-Alk) 및 (Cn-SS-Alk-Me)를 포함하지만, 이들로 제한되지는 않는다.
3' 또는 5' 표적화기 또는 연결기를 함유하는, 표 2A 및 2B에 기재된 임의의 LPA RNAi 물질은 대안적으로 3' 또는 5' 표적화기 또는 연결기를 함유하지 않을 수 있거나, 표 4에 기재된 것(이들로 제한되지는 않음)을 포함하는 상이한 3' 또는 5' 표적화기 또는 연결기를 함유할 수 있다. 표 1, 표 2A 및 표 2B에 기재된 임의의 LPA RNAi 물질 뉴클레오타이드 서열은, 변형되든 또는 변형되지 않든, 표 4에 기재된 것(이들로 제한되지는 않음)을 포함하는 3' 또는 5' 표적화기 또는 연결기를 함유할 수 있다. 표 3A 및 3B에 기재된 임의의 LPA RNAi 물질 듀플렉스는, 변형되든 또는 변형되지 않든, 표 4에 기재된 것(이들로 제한되지는 않음)을 포함하는 표적화기 또는 연결기를 추가로 포함할 수 있고, 표적화기 또는 연결기는 LPA RNAi 물질 듀플렉스의 센스 가닥 또는 안티센스 가닥 중 어느 하나의 3' 또는 5' 말단에 부착될 수 있다.
각각의 상기 구조에서, NAG는 N-아세틸-갈락토스아민 또는 또 다른 ASGPR 리간드를 포함한다. 각각의 (NAGx)는 포스페이트기((NAG25), (NAG30) 및 (NAG31)에서처럼), 또는 포스포로티오에이트기((NAG25)s, (NAG30)s 및 (NAG31)s에서처럼) 또는 또 다른 연결기를 통해 LPA RNAi 물질에 부착될 수 있다. 대안적으로, 당해 분야에 공지된 다른 연결기를 사용할 수 있다.
전달 비히클
몇몇 실시형태에서, 전달 비히클은 RNAi 물질을 세포 또는 조직으로 전달하도록 사용될 수 있다. 전달 비히클은 세포 또는 조직으로의 RNAi 물질의 전달을 개선하는 화합물이다. 전달 비히클은 중합체, 예컨대 양친매성 중합체, 막 활성 중합체, 펩타이드, 멜리틴 펩타이드, 멜리틴 유사 펩타이드(melittin-like peptide: MLP), 지질, 가역적으로 변형된 중합체 또는 펩타이드 또는 가역적으로 변형된 막 활성 폴리아민을 포함하거나 이들로 이루어지지만, 이들로 제한되지는 않는다.
몇몇 실시형태에서, RNAi 물질은 지질, 나노입자, 중합체, 리포솜, 미셀, DPC 또는 당해 분야에서 이용 가능한 다른 전달 시스템과 조합될 수 있다. RNAi 물질은 표적화기, 지질(콜레스테롤 및 콜레스테릴 유도체를 포함하지만, 이들로 제한되지는 않음), 나노입자, 중합체, 리포솜, 미셀, DPC(예를 들어, WO 제2000/053722호, WO 제2008/0022309호, WO 제2011/104169호 및 WO 제2012/083185호, WO 제2013/032829호, WO 제2013/158141호(이들은 각각 본 명세서에서 참고로 포함됨) 참조), 또는 당해 분야에서 이용 가능한 다른 전달 시스템에 또한 화학적으로 접합될 수 있다.
약제학적 조성물
포유류에서 생체내 간 세포로 LPA RNAi 물질을 전달하는 방법이 본 명세서에 기재되어 있다. 몇몇 실시형태에서, 전달 비히클을 사용할 수 있다. 전달 비히클은 세포로의 RNAi 물질의 전달을 개선하는 화합물이다. 전달 비히클은 중합체, 예컨대 양친매성 중합체, 막 활성 중합체, 펩타이드, 예컨대 멜리틴 또는 멜리틴 유사 펩타이드, 가역적으로 변형된 중합체 또는 펩타이드, 또는 지질일 수 있지만, 이들로 제한되지는 않는다. 몇몇 실시형태에서, LPA RNAi 물질은 아시알로당단백질 리간드를 포함하는 표적화 리간드에 연결된다. 몇몇 실시형태에서, LPA RNAi 물질은 갈락토스 클러스터를 포함하거나 이것으로 이루어진 표적화 리간드에 연결된다.
LPA RNAi 물질은 예를 들어 대상체에서 세포, 세포의 군 또는 조직에서 LPA의 발현을 저해하도록 사용될 수 있다. 몇몇 실시형태에서, LPA RNAi 물질은 대상체에 대한 투여를 위해 조성물, 즉 약제학적 조성물 또는 약제를 제제화하도록 사용된다. 본 명세서에 사용된 바대로, 약제학적 조성물 또는 약제는 적어도 하나의 기재된 LPA RNAi 물질 및 하나 이상의 약제학적으로 허용가능한 부형제의 약물학적 유효량을 포함한다. 약제학적으로 허용가능한 부형제(부형제들)는 안전성을 위해 적절하게 평가되고 약물 전달 시스템에서 의도적으로 포함된 활성 약제 성분(API, 치료 제품, 예를 들어, LPA RNAi 물질) 이외의 물질이다. 부형제는 의도되는 투약량에서 치료 효과를 발휘하지 않거나 발휘하도록 의도되지 않는다. 부형제는 a) 제조 동안 약물 전달 시스템의 프로세싱의 보조, b) API의 안정성, 생체이용성 또는 환자 수용성의 보호, 지원 또는 향상, c) 생성물 식별의 보조, 및/또는 d) 저장 또는 사용 동안 API의 전달의 전체 안정성, 유효성의 임의의 다른 속성의 증대에 작용할 수 있다. 약제학적으로 허용가능한 부형제는 불활성 물질이거나 아닐 수 있다.
부형제는 흡수 향상제, 피착방지제(anti-adherent), 소포제, 항산화제, 결합제, 결합제, 완충제, 캐리어, 코팅제, 색상, 전달 향상제, 전달 중합체, 덱스트란, 덱스트로스, 희석제, 붕괴제, 유화제, 증량제, 필러, 향료, 유동화제, 습윤제, 활택제, 오일, 중합체, 보존제, 식염수, 염, 용매, 당, 현탁제, 서방 매트릭스, 감미료, 증점제, 등장화제, 비히클, 방수제 및 습윤제를 포함하지만, 이들로 제한되지는 않는다.
약제학적 조성물은 약제학적 조성물에서 흔히 발견되는 다른 추가 성분을 함유할 수 있다. 이러한 추가 성분은 항소양제, 수렴제, 국소 마취제 또는 소염제(예를 들어, 항히스타민제, 다이펜하이드라민 등)을 이들로 제한되지는 않는다. 본 명세서에서 정의된 RNAi 물질을 발현하거나 포함하는 세포, 조직 또는 단리된 장기가 "약제학적 조성물"로서 사용될 수 있다는 것이 또한 고안된다. 본 명세서에 사용된 바와 같은, "약리학적 유효량", "치료학적 유효량", 또는 단순히 "유효량"은 의도된 약리학적, 치료학적 또는 예방학적 결과를 생성하는 RNAi 물질의 양을 의미한다.
몇몇 실시형태에서, 기재된 LPA RNAi 물질은 제2 LPA RNAi 물질 또는 다른 RNAi 물질, 소분자 약물, 항체, 항체 단편, 및/또는 백신(이들로 제한되지는 않음)을 포함하는 하나 이상의 추가 치유제 또는 치료와 조합된다. 추가 치유제의 예는 HMg Co-A 환원효소 저해제(스타틴), 에제티미브, PCSK-9 저해제, CTEP 저해제, ANGPTL3을 표적화하는 치료제, APOC3을 표적화하는 치료제 및 니아신을 포함하지만, 이들로 제한되지는 않는다.
기재된 RNAi 물질 및 본 명세서에 개시된 LPA RNAi 물질을 포함하는 약제학적 조성물은 키트, 용기, 팩 또는 분배기에 포장되거나 포함될 수 있다. LPA RNAi 물질 및 상기 LPA RNAi 물질을 포함하는 약제학적 조성물은 프리필드 주사기 또는 바이알에서 포장될 수 있다.
몇몇 실시형태에서, 적어도 하나의 기재된 LPA RNAi 물질을 포함하는 약제학적 조성물이 고려된다. 이 약제학적 조성물은 세포, 조직 또는 유기체에서의 LPA 유전자의 발현의 저해에서 유용하다. 몇몇 실시형태에서, 기재된 약제학적 조성물은, LPA 발현의 감소 또는 저해로부터 이익을 얻는, 질환, 병태 또는 장애를 가지는 대상체를 치료하기 위해 사용된다. 몇몇 실시형태에서, 기재된 약제학적 조성물은, LPA 발현의 감소 또는 저해로부터 이익을 얻는, 질환, 병태 또는 장애를 발생시킬 위험에 있는 대상체를 치료하기 위해 사용된다. LPA 발현의 감소 또는 저해로부터 이익을 얻는, 질환, 병태 또는 장애는 베르거 질환, 말초 동맥 질환, 관상동맥 동맥 질환, 대사 증후군, 급성 관상동맥 증후군, 대동맥판막 협착증, 대동맥판막 역류, 대동맥 박리, 망막 동맥 폐쇄, 뇌혈관 질환, 장간막 허혈, 견상장간막 동맥 폐쇄, 신동맥 협착증, 안정/불안정 협심증, 급성 관상동맥 증후군, 이형접합 또는 동형접합 가족성 고콜레스테롤혈증, 고아포베타지단백혈증, 뇌혈관 죽상동맥경화증, 뇌혈관 질환 및 정맥성 혈전증을 포함하지만, 이들로 제한되지는 않는다. 몇몇 실시형태에서, 대상체는 인간 환자(이들로 제한되지는 않음)를 포함하는 포유류이다.
본 명세서에 기재된 적어도 하나의 LPA RNAi 물질을 포함하는 세포, 조직 및 비인간 유기체가 고려된다. 세포, 조직 또는 비인간 유기체는 당해 분야에서 이용 가능한 임의의 수단에 의해 세포, 조직 또는 비인간 유기체로 RNAi 물질을 전달함으로써 만들어진다. 몇몇 실시형태에서, 세포는 인간 세포(이들로 제한되지는 않음)를 포함하는 포유류 세포이다. 세포, 조직 또는 비인간 유기체는 조사에 또는 조사 도구(예를 들어, 약물 시험 또는 진단)로서 유용하다.
치료 방법
몇몇 실시형태에서, 본 명세서에 기재된 LPA RNAi 물질은, LPA 발현의 감소 또는 저해로부터 이익을 얻는, 질환, 병태 또는 장애를 가지거나 가질 위험에 있는 대상체를 치료하기 위해 사용된다. LPA 유전자 발현의 감소 및/또는 저해로부터 이익을 얻는, 대상체의 치료는 치료학적 및/또는 예방학적 치료를 포함한다. 질환, 병태 또는 장애의 예는 베르거 질환, 말초 동맥 질환, 관상동맥 동맥 질환, 대사 증후군, 급성 관상동맥 증후군, 대동맥판막 협착증, 대동맥판막 역류, 대동맥 박리, 망막 동맥 폐쇄, 뇌혈관 질환, 장간막 허혈, 견상장간막 동맥 폐쇄, 신동맥 협착증, 안정/불안정 협심증, 급성 관상동맥 증후군, 이형접합 또는 동형접합 가족성 고콜레스테롤혈증, 고아포베타지단백혈증, 뇌혈관 죽상동맥경화증, 뇌혈관 질환 및 정맥성 혈전증을 포함하지만, 이들로 제한되지는 않는다. 몇몇 실시형태에서, 상기 방법은 치료하고자 하는 포유류에게 본 명세서에 기재된 LPA RNAi 물질을 포함는 조성물, 예컨대 약제학적 조성물을 투여하는 단계를 포함한다.
몇몇 실시형태에서, 치료학적 유효량(예를 들어, 대상체에서의 LPA의 발현을 저해하기에 효과적인 양)의 하나 이상의 기재된 LPA RNAi 물질은 대상체에게 투여되어서, 대상체에서의 LPA의 발현을 저해한다. 몇몇 실시형태에서, 본 명세서에 기재된 하나 이상의 LPA RNAi 물질은, LPA 발현의 감소 또는 저해로부터 이익을 얻는, 질환 또는 장애를 가지는 대상체를 치료하기 위해 사용된다. 몇몇 실시형태에서, 기재된 LPA RNAi 물질은, LPA 발현의 감소 또는 저해로부터 이익을 얻는, 질환 또는 장애를 가지는 대상체에서 적어도 하나의 증상을 치료하거나 예방하도록 사용된다. 대상체는 치료학적 유효량의 임의의 하나 이상의 기재된 RNAi 물질이 투여되어서 증상을 치료한다. 몇몇 실시형태에서, 대상체는 예방학적 유효량의 임의의 하나 이상의 기재된 RNAi 물질이 투여되어서 하나 이상의 증상을 예방한다.
몇몇 실시형태에서, LPA RNAi 물질은 임상 제시를 치료하거나 관리하도록 사용되고, 여기서 이러한 치료, 예방 또는 관리를 요하는 대상체는 치료학적 또는 예방학적 유효량의 본 명세서에 기재된 하나 이상의 LPA RNAi 물질 또는 LPA RNAi 물질 함유 조성물이 투여된다. 몇몇 실시형태에서, 상기 방법은 치료하고자 하는 포유류에게 본 명세서에 기재된 LPA RNAi 물질을 포함하는 조성물을 투여하는 단계를 포함한다.
몇몇 실시형태에서, 상기 방법은 제2 치료제 또는 치료를 투여하는 단계를 추가로 포함한다. 몇몇 실시형태에서, 제2 치료제는 또 다른 LPA RNAi 물질(예를 들어, LPA 표적 내의 상이한 서열을 표적화하는 LPA RNAi 물질)이다. 다른 실시형태에서, 제2 치료제는 소분자 약물, 항체, 항체 단편 및 백신을 포함하는 군으로부터 선택될 수 있다.
투여 경로는 RNAi 물질이 신체와 접촉하는 경로이다. 일반적으로, 대상체의 치료를 위해 약물 및 핵산을 전달하는 방법이 당해 분야에 널리 공지되어 있고, 본 명세서에 기재된 조성물의 투여에 적용 가능하다. 본 명세서에 기재된 화합물은 특정한 경로에 적절히 맞춰진 제제에서 임의의 적합한 경로를 통해 투여될 수 있다. 따라서, 본 명세서에 기재된 화합물은 주사에 의해, 예를 들어, 정맥내로, 근육내, 피내로, 피하로 또는 복강내로 투여될 수 있다.
몇몇 실시형태에서, 본 명세서에 기재된 LPA RNAi 물질 또는 조성물은 당해 분야에 공지된 올리고뉴클레오타이드 전달 기법을 이용하여 세포, 세포의 군, 조직 또는 대상체에게 전달될 수 있다. 일반적으로, (시험관내 또는 생체내) 핵산 분자를 전달하기 위해 당해 분야에 인식된 임의의 적합한 방법은 본 명세서에 기재된 LPA RNAi 물질에 의한 사용에 적응될 수 있다. 예를 들어, 전달은 국부 투여(예를 들어, 직접 주사, 이식 또는 국소 투여), 전신 투여, 또는 피하, 정맥내, 경구, 복강내 또는 비경구 경로, 예컨대 두개내(예를 들어, 심실내, 뇌실질내 및 척추강내), 근육내, 경피, 기도(에어로졸), 비강, 직장 또는 국소(협측 및 설하 포함) 투여에 의할 수 있다. 소정의 실시형태에서, 조성물은 피하 또는 정맥내 점적주사 또는 주사에 의해 투여될 수 있다.
몇몇 실시형태에서, RNAi 물질은 지질, 나노입자, 중합체, 리포솜, 미셀, DPC 또는 당해 분야에서 이용 가능한 다른 전달 시스템과 조합될 수 있다. RNAi 물질은 또한 표적화기, 지질(콜레스테롤 및 콜레스테릴 유도체(이들로 제한되지는 않음) 포함), 나노입자, 중합체, 리포솜, 미셀, DPC(예를 들어, WO 2000/053722, WO 2008/0022309, WO 2011/104169 및 WO 2012/083185(이들은 각각 본 명세서에 참고로 포함됨) 참조), 또는 당해 분야에서 이용 가능한 다른 전달 시스템에 화학적으로 접합될 수 있다. LPA RNAi 물질은 전달 중합체에 접합될 수 있다. 몇몇 실시형태에서, 전달 중합체는 가역적으로 마스킹된/변형된 양친매성 막 활성 폴리아민이다.
발현의 저해
본 명세서에 사용된 바와 같은, 용어 "침묵시킨다", "감소시킨다", "저해한다", "하향조절한다" 또는 "유전자 발현을 넉다운시킨다"는, LPA 유전자를 말할 때, LPA 유전자가 전사되는 세포, 세포의 군 또는 조직에서, 유전자로부터 전사된 RNA의 수준 또는 mRNA로부터 전사된 폴리펩타이드, 단백질 또는 단백질 하위단위의 수준에 의해 측정되는, 유전자의 발현이, 세포, 세포의 군 또는 조직이 이렇게 치료되거나 치료되지 않은 제2 세포, 세포의 군 또는 조직, 또는 LPA RNAi 물질의 투여 전의 동일한 세포, 세포의 군 또는 조직과 비교하여, 기재된 LPA RNAi 물질에 의해 치료될 때 감소한다는 것을 의미한다.
몇몇 실시형태에서, 기재된 LPA RNAi 물질이 투여되는 대상체에서의 유전자 발현 수준 및/또는 LPA의 mRNA 수준은 LPA RNAi 물질이 투여되기 전의 대상체 또는 LPA RNAi 물질을 받지 않는 대상체에 비해 적어도 약 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% 또는 98% 감소한다. 대상체에서의 유전자 발현 수준 및/또는 mRNA 수준은 대상체의 세포, 세포의 군, 및/또는 조직에서 감소할 수 있다. 몇몇 실시형태에서, 기재된 LPA RNAi 물질이 투여되는 대상체에서의 LPA의 단백질 수준은 LPA RNAi 물질이 투여되기 전의 대상체 또는 LPA RNAi 물질을 받지 않는 대상체에 비해 적어도 약 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% 또는 98% 감소한다. 대상체에서의 단백질 수준은 대상체의 세포, 세포의 군, 조직, 혈액, 및/또는 다른 유체에서 감소할 수 있다. 유전자 발현, mRNA 또는 단백질 수준의 감소는 당해 분야에 공지된 임의의 방법에 의해 평가될 수 있다. LPA mRNA 수준 및/또는 단백질 수준의 감소 또는 저하는 본 명세서에서 총체적으로 LPA에서의 감소 또는 저하 또는 LPA의 발현의 저해 또는 감소로 칭해진다.
세포로의 도입은, RNAi 물질을 의미할 때, 세포로 RNAi 물질을 기능적으로 전달하는 것을 의미한다. 기능적 전달이란, RNAi 물질이 세포로 전달되고, 생물학적 활성(예를 들어, 유전자 발현의 서열 특이적 저해)을 가진다는 것을 의미한다.
세포 및 조직 및 비인간 유기체
본 명세서에 기재된 LPA RNAi 물질의 적어도 하나를 포함하는 세포, 조직 및 비인간 유기체가 고려된다. 세포, 조직 또는 비인간 유기체는 세포, 조직, 또는 비인간 유기체로 RNAi 물질을 전달함으로써 만들어진다.
상기 제공된 실시형태 및 항목은 하기 비제한적인 실시예에 의해 이제 예시된다.
실시예
실시예 1. RNAi 물질 합성.
A) 합성. LPA RNAi 물질을 올리고뉴클레오타이드 합성에서 사용된 고상에서 포스포르아미다이트 기법에 따라 합성하였다. 스케일에 따라, MerMade96E(Bioautomation) 또는 MerMade12(Bioautomation)를 사용하였다. 제어 기공 유리(CPG, 500Å 또는 600Å, Prime Synthesis(미국 펜실베니아주 아스톤)로부터 얻음)로 제조된 고체 지지체에서 합성을 수행하였다. 모든 DNA, 2' 변형된 RNA, 및 UNA 포스포르아미다이트를 Thermo Fisher Scientific(미국 위스콘신주 밀워키))으로부터 구입하였다. 구체적으로, 하기 2'-O-메틸 포스포르아미다이트를 사용하였다: (5'-O-다이메톡시트리틸-N6-(벤조일)-2'-O-메틸-아데노신-3'-O-(2-사이아노에틸-N,N-다이아이소프로필-l아미노) 포스포르아미다이트, 5'-O-다이메톡시-트리틸-N4-(아세틸)-2'-O-메틸-사이티딘-3'-O-(2-사이아노에틸-N,N-다이아이소프로필-아미노) 포스포르아미다이트, (5'-O-다이메톡시트리틸-N2-(아이소뷰티릴)-2'-O-메틸-구아노신-3'-O-(2-사이아노-에틸-N,N-다이아이소프로필아미노)포스포르아미다이트 및 5'-O-다이메톡시-트리틸-2'-O-메틸-우리딘-3'-O-(2-사이아노에틸-N,N-다이아이소프로필아미노)포스포르아미다이트. 2'-데옥시-2'-플루오로-포스포르-아미다이트는 2'-O-메틸 RNA 아미다이트와 동일한 보호기를 보유하였다. 하기 UNA 포스포르아미다이트를 사용하였다: 5'-(4,4'-다이메톡시트리틸)-N-벤조일-2',3'-세코-아데노신, 2'-벤조일-3'-[(2-사이아노에틸)-(N,N-다이아이소프로필)]-포스포르-아미다이트, 5'-(4,4'-다이메톡시트리틸)-N-아세틸-2',3'-세코-시토신, 2'-벤조일-3'-[(2-사이아노에틸)-(N,N-다이아이소-프로필)]-포스포르아미다이트, 5'-(4,4'-다이메톡시트리틸)-N-아이소뷰티릴-2',3'-세코-구아노신, 2'-벤조일-3'-[(2-사이아노에틸)-(N,N-다이아이소프로필)]-포스포르아미다이트 및 5'-(4,4'-다이메톡시-트리틸)-2',3'-세코-우리딘, 2'-벤조일-3'-[(2-사이아노에틸)-(N,N- 다이아이소-프로필)]-포스포르아미다이트. 모든 아미다이트를 무수 아세토나이트릴(50mM) 중에 용해시키고, 분자체(3Å)를 첨가하였다. 올리고머의 5' 말단에서 TEG-콜레스테롤을 도입하기 위해, Glen Research(미국 버지니아주 스털링))로부터의 1-다이메톡시트리틸옥시-3-O-(N-콜레스테릴-3-아미노프로필)-트라이에틸렌글라이콜-글라이세릴-2-O-(2-사이아노에틸)-(N,N,-다이아이소프로필)-포스포르아미다이트를 사용하였다. 합성 사이클의 어떤 변형 없이 5'-변형을 도입하였다. 5-벤질티오-1H-테트라졸(BTT, 아세토나이트릴 중의 250mM)을 활성제 용액으로서 사용하였다. 커플링 시간은 10분(RNA), 180초(콜레스테롤), 90초(2'OMe 및 UNA) 및 60초(2'F 및 DNA)였다. 포스포로티오에이트 연결을 도입하기 위해, 무수 아세토나이트릴 중의 3-페닐 1,2,4-다이티아졸린-5-온(POS, PolyOrg, Inc.(미국 매사추세츠주 레민스터)로부터 얻음)의 100mM의 용액을 사용하였다. 특정한 서열에 대해 표 1, 표 2A 및 표 2B를 참조한다.
B. 지지체 결합된 올리고머의 절단 및 탈보호. 고상 합성의 마무리 후, 건조된 고체 지지체를 30℃에서 2시간 동안 물 및 28% 수산화암모늄 용액(Aldrich) 중의 40중량% 메틸아민의 1:1 용적 용액에 의해 처리하였다. 용액을 증발시키고, 고체 잔류물을 물 중애 재구성하였다(하기 참조).
C. 정제. Waters XBridge BEH300 C4 5u Prep 컬럼 및 Shimadzu LC-8 시스템을 사용하여 미정제 콜레스테롤 함유 올리고머를 역상 HPLC에 의해 정제하였다. 완충제 A는 100mM의 TEAA(pH 7.5)이고 5% 아세토나이트릴을 함유하였고, 완충제 B는 100mM의 TEAA이고 95% 아세토나이트릴을 함유하였다. 260㎚에서의 UV 트레이스를 기록하였다. 이후, 100mM의 중탄산암모늄(pH 6.7) 및 20% 아세토나이트릴의 실행 완충제와 함께 Sephadex G-25 매질이 충전된 GE Healthcare XK 16/40 컬럼을 사용하여 크기 배제 HPLC에서 적절한 분획을 실행하였다. TKSgel SuperQ-5PW 13u 컬럼 및 Shimadzu LC-8 시스템을 사용하여 음이온성 교환 HPLC에 의해 다른 미정제 올리고머를 정제하였다. 완충제 A는 20mM의 Tris, 5mM의 EDTA(pH 9.0)이고, 20% 아세토나이트릴을 함유하고, 완충제 B는 1.5M 염화나트륨의 첨가에 의해 완충제 A와 동일하였다. 260㎚에서의 UV 트레이스를 기록하였다. 적절한 분획을 혼주하고, 이후 콜레스테롤 함유 올리고머에 기재된 바대로 크기 배제 HPLC에서 실행하였다.
D. 어닐링. 0.2x PBS(포스페이트 완충 식염수, 1x, Corning, Cellgro) 중의 등몰량 용액(센스 및 안티센스)을 합함으로써 상보성 균주를 혼합하여 RNAi 물질을 형성하였다. 이 용액을 70℃에서 열혼합기(thermomixer)로 위치시키고, 95℃로 가열하고, 95℃에서 5분 동안 유지시키고, 실온으로 천천히 냉각시켰다. 약간의 RNAi 물질을 동결건조시키고, -15 내지 -25℃에서 저장하였다. 0.2x PBS 중의 UV-Vis 분광계에서 용액 흡광도를 측정함으로써 듀플렉스 농도를 결정하였다. 이후, 260㎚에서의 용액 흡광도에 전환 인자 및 희석 인자를 곱하여 듀플렉스 농도를 결정하였다. 달리 기재되지 않은 한, 모든 전환 인자는 0.037㎎/(㎖ㆍ㎝)이었다. 약간의 실험을 위해, 실험으로 결정된 흡광 계수로부터 전환 인자를 계산하였다.
실시예 2. LPA RNAi 물질의 1차 시험관내 분석. 인실리코 분석에 의해 인간 및 비인간 영장류 교차반응성으로 확인된 후보 서열을 스크리닝하였다. 108개의 인실리코 확인된 잠재적인 LPA RNAi 물질을 합성하고, 3개의 그룹에서 시험관내 효율에 대해 스크리닝하였다. 스크리닝 목적을 위해, 인간 LPA cDNA 서열(수탁 번호 NM_005577.1)을 상업적으로 구입 가능한 포유류 발현 벡터(Origene(메릴랜드 로크빌))로부터 상업적으로 구입 가능한 리포터 기반 스크리닝 플라스미드인 psiCHECK2(Promega(미국 위스콘신주 매디슨))로 서브클로닝하고, 이 플라스미드는 레닐라 루시퍼라제/LPA 융합 mRNA를 생성하였다. 인간 배경에서의 LPA RNAi 물질 효율을 위해, 인간 간세포 암종 세포주인 Hep3B 세포를 96웰 포맷에서 웰마다 약 10,000개의 세포로 플레이팅하였다. 각각의 108개의 LPA RNAi 물질을 웰마다 50-100ng의 LPA-psiCHECK2 플라스미드 DNA 및 웰마다 0.2㎕ 리포펙타민(LipoFectamine) 2000과 함께 2 또는 3의 농도(1nM 및 0.1nM, 또는 0.02, 0.2 및 2nM)에서 동시형질감염시켰다. 이중 루시퍼라제 리포터 검정(Promega(미국 위스콘신주 매디슨))을 이용하여 psiCHECK2 플라스미드에 또한 존재하는 구성적으로 발현된 반딧불이 루시퍼라제의 수준으로 정규화된 레닐라 루시퍼라제 수준을 측정함으로써 유전자 넉다운을 결정하였다(표 5A 및 표 5B).
실시예 3. LPA RNAi 물질 EC 50 결정. 150fM-3nM의 범위의 LPA RNAi 물질 농도에 의해 동일한 세포 및 형질감염 조건을 이용하여 10점 EC50 곡선을 생성하였다. 그래프패드 프리즘(GraphPad Prism) 소프트웨어를 이용하여 EC50을 결정하였다(표 6).
실시예 4. 구조-활성 관계(Structure-Activity Relationship: SAR ) 설계된 LPA RNAi 물질의 시험관내 분석. LPA RNAi 물질 SAR 세트(AD01532에 기초한 364개의 서열 및 AD01533에 기초한 351개의 서열)를 합성하고, 시험관내 효율에 대해 스크리닝하였다. 스크리닝 목적을 위해, KIV-3으로부터 KIV-9로의 인간 LPA cDNA 서열의 2756bp(수탁 번호 NM_005577.1)를 합성하고, psiCHECK2(Promega(위스콘신주 매디슨))인, 상업적으로 구입 가능한 리포터 기반 스크리닝 플라스미드로 클로닝하고(GeneWiz(뉴저지주 사우스 플레인필드)), 이 플라스미드는 레닐라 루시퍼라제/LPA 융합 mRNA를 생성하였다. 인간 배경에서의 LPA RNAi 물질 효율을 위해, 인간 간세포 암종 세포주인 HuH7 세포를 96웰 포맷에서 웰마다 약 7500개의 세포로 플레이팅하였다. 각각의 LPA RNAi 물질을 웰마다 25ng의 LPA-psiCHECK2 플라스미드 DNA 및 웰마다 0.2㎕ 리포펙타민 2000과 함께 2의 농도(1nM 및 0.1nM, 또는 10nM 및 1nM)에서 동시형질감염시켰다. 이중 루시퍼라제 리포터 검정(Promega(미국 위스콘신주 매디슨))을 이용하여 psiCHECK2 플라스미드에 또한 존재하는 구성적으로 발현된 반딧불이 루시퍼라제의 수준으로 정규화된 레닐라 루시퍼라제 수준을 측정함으로써 유전자 넉다운을 결정하였다(표 7A 및 표 7B).
실시예 5. 일시적 형질전환 및 형질전환 마우스에서의 RNAi 물질 효율의 생체내 분석.
A) 투여 및 샘플 수집. 생체내 LPA RNAi 물질의 효율을 평가하기 위해, 일시적 형질전환 마우스를 사용하였다. 콜레스테롤 접합된 LPA RNAi 물질 투여 전 적어도 30일에, 야생형 마우스에 마우스 알부민 프로모터의 제어 하에 SEAP 유전자를 함유하는 플라스미드에 의해 수력 꼬리 정맥 주사에 의해 주사하였다. LPA 유전자 표적 서열을 플라스미드의 3' UTR에서 클로닝하였다. 이 마우스는 SEAP-LPA HTV 마우스로 기재된다. 1일에 MLP 전달 중합체를 사용하여 마우스에 콜레스테롤 접합된 LPA RNAi 물질을 투여하였다(WO 2012/083185, 본 명세서에 참고로 포함됨; 멜리틴을 합성하고 CDM-NAG에 의해 변형시켜 여기 기재된 바와 같은 MLP 전달 중합체를 생성하였다). 각각의 마우스는 LPA RNAi 물질 + MLP 전달 중합체의 용량을 함유하는 200-250㎕의 용액(대부분의 경우에 1:1 w/w RNAi 물질: MLP 전달 중합체)의 정맥내(IV) 주사를 받았다. 몇몇 실험에서, LPA RNAi 물질을 전달 중합체에 직접적으로 접합하였다. 중합체 접합된 LPA RNAi 물질을 꼬리 정맥에 유사하게 주사하였다. 표시된 LPA RNAi 물질(표 8B)을 54.4% 에폭시 에틸 아미노 아크릴레이트(EEAA) 아민 단량체 및 45.6% 프로필 아크릴레이트 프로필 단량체(MW 41962g/mol, WO 2013/158141에 기재된 바대로 합성된 중합체)를 가지는 ARF1164-106A-5인 폴리아크릴레이트 중합체에 접합하고, 3x ACit-NAG, 6x ACit-PEG(WO 2012/092373 및 PCT/US16/34512에 기재된 바대로 마스킹된 중합체)에 의해 마스킹하였다. -4일 또는 -1일에 주사 전 마우스로부터 대조군 혈청(전처리) 샘플을 취했다. 4일, 8일, 15일, 22일, 29일, 36일 및 43일에 마우스로부터 주사 후 혈청 샘플을 취했다. 몇몇 마우스의 경우, 4일 대신에 3일 또는 5일에 샘플을 수집하였다.
추가의 실험에서, 완전 길이 LPA를 발현하는 일시적 형질전환 마우스를 사용하여 LPA RNAi 물질을 생체내 평가하였다. 콜레스테롤 표적화된 LPA RNAi 물질 투여 전 적어도 30일에, 면역 손상된(Nod.scid) 마우스에 마우스 알부민 프로모터의 제어 하에 LPA cDNA를 함유하는 미니사이클에 의해 수력 꼬리 정맥 주사에 의해 주사하였다. 이 마우스는 LPA mc HTV 마우스로 기재된다. 콜레스테롤 표적화된 또는 NAG(또한 GalNAc라 칭함) 접합된 LPA RNAi 물질을 1일에 마우스에 투여하였다. 콜레스테롤 표적화된 RNAi 물질을 위해, 각각의 마우스는 RNAi 물질 + MLP 전달 중합체의 용량을 함유하는 200-250㎕ 용액(1:1 w/w RNAi 물질:MLP 전달 중합체)의 꼬리 정맥으로 정맥내(IV) 주사를 받았다. NAG 접합된 LPA RNAi 물질에 대해, 마우스는 완충 식염수 중에 RNAi 물질의 용량을 함유하는 300㎕의 용액의 어깨 사이의 등에서 쳐진 피부로 피하(SC) 주사를 받았다. 몇몇 샘플의 경우, LPA RNAi 물질을 MLP 전달 펩타이드와 함께 또는 이것 없이 투여하였다. MLP 전달 펩타이드에 의해 전달된 RNAi 물질을 용량 of RNAi 물질 + MLP 전달 중합체의 용량을 함유하는 200-250㎕ 용액(대부분의 경우에 1:2 w/w RNAi 물질: MLP 전달 중합체)의 꼬리 정맥으로 정맥내(IV) 주사에 의해 투여하였다. -4일 또는 -1일에 주사 전 마우스로부터 대조군 혈청(전처리) 샘플을 취했다. 4일, 8일, 15일, 22일, 29일, 36일 및 43일에 마우스로부터 주사 후 혈청 샘플을 취했다. 몇몇 마우스의 경우, 4일 대신에 3일 또는 5일에 샘플을 수집하였다.
추가의 실험에서, LPA RNAi 물질을 아포(a) 및 Lp(a) 형질전환 마우스에 투여하였다(Frazer KA et al 1995, Nature Genetics 9:424-431). 이 마우스는, 추가 서열 5' 및 3' 둘 다를 가지는, (아포(a) 단백질을 코딩하는) 완전 LPA 유전자를 함유하는 YAC로부터 인간 아포(a)를 발현한다. 아포(a) YAC 함유 마우스를 인간 아포B-100 발현 마우스에 교잡함으로써 Lp(a) 마우스를 교배하였다(Callow MJ et al 1994, PNAS 91:2130-2134). 콜레스테롤 표적화된 RNAi 물질 및 NAG 접합된 RNAi 물질을 상기 기재된 바대로 투여하였다. -1일에 주사 전 마우스로부터 대조군 혈청(전처리) 샘플을 취했다. 4일, 8일, 15일, 22일, 29일, 36일, 43일, 50일, 57일 및 64일에 마우스로부터 주사 후 혈청 샘플을 취했다.
B) LPA 발현 넉다운 분석. SEAP-LPA HTV 마우스에 대해, Phospha-Light(상표명), 화학발광 리포터 유전자 검정 시스템(Life Technologies)을 사용하여 마우스로부터의 혈청을 평가함으로써 혈청 중의 SEAP 단백질 수준을 모니터링하였다. 정규화를 위해, "전처리로 정규화된" 발현의 비율을 결정하도록 소정의 시점에 각각의 동물에 대한 SEAP 수준을 그 동물에서의 발현의 전처리 수준에 의해 나눴다. 이후, 군 내의 개인 사이에 특정한 시점에서의 발현을 평균하였다.
LPA mc HTV 마우스 및 형질전환 마우스를 위해, 아포(a)(Abcam)에 대해 ELISA를 이용하여 마우스로부터의 혈청을 평가함으로써 혈청 중의 인간 아포(a) 단백질 수준을 모니터링하였다. 정규화를 위해, "1일로 정규화된" 발현의 비율을 결정하도록 시점에 각각의 동물에 대한 아포(a) 수준을 (이 경우에 1일에) 그 동물에서의 발현의 전처리 수준에 의해 나눴다. 이후, 식염수 대조군에서의 모든 마우스의 평균 "1일로 정규화된" 비율에 의해 개별 동물에 대한 "1일로 정규화된" 비율을 나누어서, 특정한 시점에서의 발현을 식염수 대조군으로 정규화하였다. 이것은 대조군에서의 것에 정규화된 각각의 시점에 대한 발현을 발생시킨다.
제조사의 추천에 따라 Cobas Integra 400(Roche Diagnostics)에서 Lp(a) 수준을 결정하였다. 정규화를 위해, "1일로 정규화된" 발현의 비율을 결정하도록 시점에 각각의 동물에 대한 아포(a) 수준을 (이 경우에 1일에) 그 동물에서의 발현의 전처리 수준에 의해 나눴다. 이후, 식염수 대조군에서의 모든 마우스의 평균 "1일로 정규화된" 비율에 의해 개별 동물에 대한 "1일로 정규화된" 비율을 나누어서, 특정한 시점에서의 발현을 식염수 대조군으로 정규화하였다. 이것은 대조군에서의 것에 정규화된 각각의 시점에 대한 발현을 발생시킨다.
실시예 6. LPA RNAi 물질의 생체내 스크리닝 및 SEAP 넉다운의 시간 과정. 콜레스테롤 접합된 LPA RNAi 물질을 상기 기재된 바대로 일시적 형질전환 마우스에 투여하였다. 각각의 마우스는 8㎎/㎏의 MLP 전달 중합체와 함께 8㎎/㎏의 LPA RNAi 물질의 단일 정맥내(IV) 용량을 받았다. 36일까지 동안 혈청 중의 SEAP 단백질 수준을 모니터링하였다. 넉다운 수준 및 반응의 기간은 표 9에 기재되어 있다. 시험된 모든 LPA RNAi 물질의 투여 후 85% 초과의 SEAP 혈청 단백질 수준의 감소가 얻어졌고, 시험된 LPA RNAi 물질의 모두가 아닌 2개는 99.4% 넉다운 초과를 나타냈다. AD01196 및 AD01199는 36일에 95% 초과의 넉다운을 나타냈다.
실시예 7. 생체내 스크리닝 LPA RNAi 물질 및 더 낮은 LPA RNAi 물질 용량에서의 LPA 넉다운의 시간 과정. 콜레스테롤 접합된 LPA RNAi 물질을 상기 기재된 바대로 일시적 형질전환 마우스에 투여하였다. 각각의 마우스는 2㎎/㎏의 MLP 전달 중합체와 함께 2㎎/㎏의 LPA RNAi 물질의 단일 정맥내(IV) 용량을 받았다. 43일까지 동안 혈청 중의 SEAP 단백질 수준을 모니터링하였다(표 10).
실시예 8. 아포(a) 형질전환( Tg ) 마우스에서의 LPA RNAi 물질의 생체내 시험. AD01196을 상기 기재된 바대로 마우스에 투여하였다. 각각의 마우스는 2㎎/㎏의 MLP 전달 중합체 또는 식염수와 함께 2㎎/㎏의 LPA RNAi 물질의 단일 정맥내(IV) 용량을 받았다. 64일까지 동안 혈청 중의 인간 아포(a)(아포(a)) 수준을 모니터링하였다(표 11). 15일에, 식염수 군에서의 동물은 2㎎/㎏ of MLP 전달 중합체와 함께 2㎎/㎏의 대조군 마우스 VII 인자(F7) RNAi 물질의 단일 IV 용량을 받았다. 22일에, 모든 동물에서 F7 수준을 측정하였다. 혈청 아포(a) 수준에 대한 효과 없이, 투약 후 7일에 99%까지 F7 활성을 넉다운하였다. AD01196은 천저에서 아포(a) 수준의 3 초과의 log10 넉다운을 나타냈고, 3주 후 80% 초과의 넉다운이 관찰되었다(표 11).
실시예 9. MLP 전달 중합체에 의한 LPA RNAi 물질 전달 후 비인간 영장류에서의 아포지단백 (a)( 아포 (a)) 넉다운. MLP 전달 중합체 및 LPA RNAi 물질을 만들고, 상기 기재된 바대로 약제학적으로 허용가능한 완충제 중에 합했다. 1일에, 2마리의 사이노몰거스 마카크(마카카 바스찌쭐라리스(Macaca fascicularis)) 영장류(수컷 둘 다, 각각 5.0㎏ 및 8.15㎏)에 2㎎/㎏의 AD01196 + 2㎎/㎏의 MLP 전달 중합체에 의해 주사하였다. 각각의 주사를 위해, 22 내지 25 게이지 정맥내 카테터를 사용하여 LPA RNAi 물질 + MLP 전달 중합체(2ml/㎏)를 대복제정맥에 주사하였다. (표 12에 표시된) 표시된 시점에, 혈액 샘플을 채혈하고, 아포(a) 수준, 지질 수준 및 독성 마커에 대해 분석하였다. 대퇴 정맥으로부터 혈액을 수집하고, 모든 혈액 수집 전에 영장류를 공복시켰다. Meriter laboratories에서 자동화 화학 분석장치에서 혈액 요소 질소(BUN), 알라닌 아미노기전이효소(ALT), 아스파르테이트 아미노전환효소(AST), 크레아티닌, 총 콜레스테롤(TC) 및 트라이글리세라이드(TG)에 대한 혈액 시험을 수행하였다. 자동화 화학 분석장치에서 지단백(a)(Lp(a)) 및 저밀도 지단백(LDL)에 대한 혈액 시험을 측정하였다. ELISA에 의해 혈청 아포(a) 수준을 측정하였다. 아포(a)의 상당한 넉다운이 22일에 관찰된 94.5%의 평균 최대 넉다운에 의해 관찰되었다. Lp(a)의 평균 최대 넉다운이 15일에 91.5% 관찰되었다(도 3). 치료된 동물에서 용량 관련 독성이 관찰되지 않았다.
실시예 10. NAG 접합된 LPA RNAi 물질의 생체내 스크리닝 및 넉다운의 시간 과정. NAG 접합된 LPA RNAi 물질을 상기 기재된 바대로 일시적 형질전환 마우스에 투여하였다. 각각의 마우스는 1㎎/㎏의 MLP 전달 중합체와 함께 2㎎/㎏의 LPA RNAi 물질의 단일 정맥내(IV) 용량, 또는 10㎎/㎏의 NAG 접합된 LPA RNAi 물질의 단일 피하(SC) 용량을 받았다. 22일까지 동안 혈청 중의 SEAP 단백질 수준을 모니터링하였다. 넉다운 수준 및 반응의 기간은 표 14-15에 기재되어 있다. AD01529, AD01532 및 AD01533는 MLP 전달 중합체에 의한 IV 투여 후 SEAP 수준의 85% 이상의 넉다운 및 단독의 NAG 접합된 LPA RNAi 물질의 SC 투여 후 SEAP 수준의 60% 이상의 최대 넉다운을 나타냈다.
실시예 11. 변형된 NAG 접합된 LPA RNAi 물질의 생체내 스크리닝 및 넉다운의 시간 과정. 표시된 NAG 접합된 LPA RNAi 물질을 상기 기재된 바대로 SEAP-LPA HTV 마우스에 투여하였다. 각각의 마우스는 10㎎/㎏의 NAG 접합된 LPA RNAi 물질의 단일 피하(SC) 용량을 받았다. 22일까지 동안 혈청 중의 SEAP 단백질 수준을 모니터링하였다. 넉다운 수준 및 반응의 기간은 표 16 내지 표 17에 기재되어 있다. AD01765 및 AD01768은 89%의 넉다운 활성을 나타냈다.
실시예 12. 아포(a) Tg 마우스에서의 NAG 접합된 LPA RNAi 물질의 생채내 시험. NAG 접합된 LPA RNAi 물질을 상기 기재된 바대로 아포(a) Tg 마우스에 투여하였다. 각각의 마우스는 10㎎/㎏의 LPA RNAi 물질 또는 식염수의 단일 피하(SC) 용량을 받았다. 일까지 동안 혈청 중의 인간 아포(a)(아포(a)) 수준을 모니터링하였다(표 18). AD01765는 8일에 96%의 넉다운으로 아포(a) 수준의 가장 큰 넉다운을 나타내고, 74% 초과의 넉다운이 투약 후 3주에 관찰되었다.
실시예 13. LPA mc HTV 마우스에서의 NAG 접합된 LPA RNAi 물질의 생체내 시험. 표시된 NAG 접합된 LPA RNAi 물질을 상기 기재된 바대로 LPA mc HTV 마우스에 투여하였다. 각각의 마우스는 10㎎/㎏의 LPA RNAi 물질 또는 식염수의 단일 피하(SC) 용량을 받았다. 4일에 혈청 중의 인간 아포(a)(아포(a)) 수준을 분석하였다(표 19). AD02001, AD01765 및 AD01768은 4일에 90% 초과의 넉다운을 나타냈다.
실시예 14. MLP 전달 중합체에 의한 LPA RNAi 물질 전달 후 비인간 영장류에서의 아포지단백 (a)( 아포 (a)) 넉다운. MLP 전달 중합체 및 LPA RNAi 물질을 만들고, 약제학적으로 허용가능한 완충제 중에 합했다. 1일 및 71일에, 2마리의 사이노몰거스 마카크(마카카 바스찌쭐라리스) 영장류에 4㎎/㎏의 AD01196 + 4㎎/㎏의 MLP 전달 중합체 또는 6㎎/㎏의 AD01196 + 6㎎/㎏의 MLP 전달 중합체를 주사하였다. 각각의 주사를 위해, 22 내지 25 게이지 정맥내 카테터를 사용하여 LPA RNAi 물질 + MLP 전달 중합체를 대복제정맥에 주사하였다. 표시된 시점에(도 4), 혈액 샘플을 채혈하고, 이전에 기재된 바대로 아포(a) 수준, 지질 수준 및 독성 마커에 대해 분석하였다. 아포(a)의 상당한 넉다운이 제1 용량 후 15일에 4㎎/㎏ 용량에 대해 96%의 평균 최대 넉다운에 의해 관찰되고, 15일에 관찰된 6㎎/㎏ 용량에 대해 96%가 관찰되었다. 제1 용량 후 Lp(a)의 평균 최대 넉다운은 29일에 4㎎/㎏ 용량에 대해 98.5% 및 22일에 6㎎/㎏ 용량에 대해 98.5%이었다. 치료된 동물에서 용량 관련 독성이 관찰되지 않았다.
실시예 15. Lp (a) Tg 마우스-용량 반응에서의 NAG 접합된 LPA RNAi 물질의 생체내 시험. NAG 접합된 LPA RNAi 물질을 상기 기재된 바대로 Lp(a) Tg 마우스에 투여하였다. 각각의 마우스는 0.5㎎/㎏ 또는 2㎎/㎏의 용량 수준의 LPA RNAi 물질 또는 식염수의 단일 피하(SC) 용량을 받았다. 43일까지 혈청 중의 Lp(a) 수준을 모니터링하였다(도 1, 도 2). 모든 LPA RNAi 물질은 더 높은 용량에 의한 용량-반응을 보여주어서, 15일과 22일 사이의 천저에 의해 더 큰 넉다운을 보여준다.
실시예 16. 아포(a) 특이적 LPA RNAi 물질 분자 전달 후 비인간 영장류에서의 아포지단백 (a)( 아포 (a)) 넉다운. LPA RNAi 물질을 피하(SC) 주사에 대해 본 명세서에 기재된 바대로 약제학적으로 허용가능한 완충제 중에 제조하였다. 1일, 7일 및 15일에, 2마리의 사이노몰거스 마카크(마카카 바스찌쭐라리스) 영장류에 3㎎/㎏의 AD02713, AD02819, AD02820 또는 AD02821을 피하로 주사하였다. 또한, 57일 및 85일에 AD02819 치료된 원숭이를 3㎎/㎏의 AD02819에 의해 다시 투약하였다. 혈액 샘플을 채혈하고, 이전에 기재된 바대로 아포(a) 수준, 지질 수준 및 독성 마커에 대해 분석하였다. Lp(a)의 상당한 넉다운이 43일에 AD02713에 대해 89%, 36일에 AD02819에 대해 87%, 36일에 AD02820에 대해 79% 및 29일에 AD02821에 대해 95%의 평균 최대 넉다운에 의해 관찰되었다(도 5). 실험의 시간에 걸쳐 치료된 동물에서 용량 관련 독성이 관찰되지 않았다.
실시예 17. LPA RNAi 물질 전달 후 비인간 영장류에서의 아포지단 백(a)(아포(a)) 넉다운. LPA RNAi 물질을 피하(SC) 주사에 대해 본 명세서에 기재된 바대로 약제학적으로 허용가능한 완충제 중에 제조하였다. 1일에, 2마리의 사이노몰거스 마카크(마카카 바스찌쭐라리스) 영장류에 3㎎/㎏의 AD03272, AD03462, AD03549, AD03547, AD03668, AD03460 또는 AD03536을 피하로 주사하였다. 또한, 48일에 AD03460 및 AD03536 처리된 원숭이를 1㎎/㎏의 각각의 LPA RNAi 물질에 의해 다시 투약하였다. 혈액 샘플을 채혈하고, 이전에 기재된 바대로 아포(a) 수준, 지질 수준 및 독성 마커에 대해 분석하였다. Lp(a)의 상당한 넉다운이 15일에 AD03272에 대해 62%, 15일에 AD03462에 대해 28%, 29일에 AD03549에 대해 47%, 15일에 AD03547에 대해 44%, 22일에 AD03668에 대해 53%, 29일에 AD03460에 대해 79% 및 22일에 AD03536에 대해 71%의 평균 최대 넉다운에 의해 관찰되었다(도 6). 실험의 시간에 걸쳐 치료된 동물에서 용량 관련 독성이 관찰되지 않았다.
실시예 18. 아포(a) 특이적 LPA RNAi 물질 분자 전달 후 영장류에서의 아포지단백(a)(아포(a)) 넉다운. LPA RNAi 물질을 만들고, 피하(SQ) 주사에 대해 상기 기재된 바대로 약제학적으로 허용가능한 완충제 중에 합했다. 1일에, 사이노몰거스 마카크(마카카 바스찌쭐라리스) 영장류에 식염수 또는 2㎎/㎏의 AD03460, AD03536, AD03851, AD03853 또는 AD04110을 피하로 주사하였다. 혈액 샘플을 채혈하고, 이전에 기재된 바대로 8일 및 15일에 아포(a) 수준, 지질 수준 및 독성 마커에 대해 분석하였다. Lp(a) 수준을 3개의 투약전 값의 평균으로 정규화하였다.
SEQUENCE LISTING
<110> Arrowhead Pharmaceuticals, Inc.
Stacey Melquist
Steven Kanner
David B. Rozema
David L. Lewis
Lauren J. Almeida
Darren H. Wakefield
Vladimir S. Trubetskoy
Tao Pei
Zhen Li
Aaron Almeida
<120> Compositions and Methods for Inhibiting Gene Expression
of LPA
<130> 30628-WO1
<150> 62235816
<151> 2015-10-01
<160> 1285
<210> 1
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 1
tcggcagucc cuucugcgut t 21
<210> 2
<211> 21
<212> DNA
<213>artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 2
tguagcacuc cugcacccct t 21
<210> 3
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 3
taauaagggg cugccacagt t 21
<210> 4
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 4
tuaacaauaa ggggcugcct t 21
<210> 5
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 5
tguauaacaa uaaggggcut t 21
<210> 6
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 6
tcguauaaca auaaggggct t 21
<210> 7
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 7
tcgucugagc auugugucat t 21
<210> 8
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 8
tgcgucugag cauuguguct t 21
<210> 9
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 9
tugcgucuga gcauugugut t 21
<210> 10
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 10
tucugcgucu gagcauugut t 21
<210> 11
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 11
tggaucugga uuucggcagt t 21
<210> 12
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 12
tcaggaucug gauuucggct t 21
<210> 13
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 13
tcaucugagc aucgugucat t 21
<210> 14
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 14
tgcaucugag caucguguct t 21
<210> 15
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 15
tugcaucuga gcaucgugut t 21
<210> 16
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 16
tucugcaucu gagcaucgut t 21
<210> 17
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 17
taaagccucu aggcuuggat t 21
<210> 18
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 18
tguaccccgg ggguuuccut t 21
<210> 19
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 19
tuguaccccg gggguuucct t 21
<210> 20
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 20
tcuguacccc ggggguuuct t 21
<210> 21
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 21
tuccauaaug guaguagcat t 21
<210> 22
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 22
tguccauaau gguaguagct t 21
<210> 23
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 23
tcucugucca uaaugguagt t 21
<210> 24
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 24
tcgacuaugc ugguguggut t 21
<210> 25
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 25
tccgacuaug cugguguggt t 21
<210> 26
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 26
tuccgacuau gcuggugugt t 21
<210> 27
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 27
tgguccgacu augcuggugt t 21
<210> 28
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 28
tuuucugggg uccgacuaut t 21
<210> 29
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 29
tuuuucuggg guccgacuat t 21
<210> 30
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 30
tgcgaaucuc agcaucuggt t 21
<210> 31
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 31
tccaagggcg aaucucagct t 21
<210> 32
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 32
taccaagggc gaaucucagt t 21
<210> 33
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 33
tcaccaaggg cgaaucucat t 21
<210> 34
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 34
tacaccaagg gcgaaucuct t 21
<210> 35
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 35
tccugacacu gggauccaut t 21
<210> 36
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 36
tugcaaggac acuugauuct t 21
<210> 37
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 37
tuugcaagga cacuugauut t 21
<210> 38
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 38
tuugcuccgu uggugcuuct t 21
<210> 39
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 39
taaugagccu cgauaacuct t 21
<210> 40
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 40
tgaaugagcc ucgauaacut t 21
<210> 41
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 41
tggauaauau ucuguuguct t 21
<210> 42
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 42
tccaugguau aacaccaagt t 21
<210> 43
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 43
tgauccaugg uauaacacct t 21
<210> 44
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 44
tauugggauc caugguauat t 21
<210> 45
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 45
tcauugggau ccaugguaut t 21
<210> 46
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 46
tacauuggga uccaugguat t 21
<210> 47
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 47
tgacauuggg auccauggut t 21
<210> 48
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 48
tgacauugug ucagguugct t 21
<210> 49
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 49
tcacuggaca uugugucagt t 21
<210> 50
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 50
tacuugauuc ugucacuggt t 21
<210> 51
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 51
tgagaaugag ccucgauaat t 21
<210> 52
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 52
tccauuuggg uaguauucut t 21
<210> 53
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 53
tcaccauuug gguaguauut t 21
<210> 54
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 54
tccaccauuu ggguaguaut t 21
<210> 55
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 55
tauaacacca agggcgaaut t 21
<210> 56
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 56
tacugggauc caugguauat t 21
<210> 57
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 57
tcacugggau ccaugguaut t 21
<210> 58
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 58
taccaccgug ggaguugugt t 21
<210> 59
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 59
tcaagacuga cauguucuut t 21
<210> 60
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 60
tgggaguugu gaggacacut t 21
<210> 61
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 61
tucucaggug gugcuuguut t 21
<210> 62
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 62
tcacagggcu uuucucaggt t 21
<210> 63
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 63
tgaugccagu gugguaucat t 21
<210> 64
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 64
tugaugccag ugugguauct t 21
<210> 65
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 65
tgacaccuga uucuguuuct t 21
<210> 66
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 66
tggacaccug auucuguuut t 21
<210> 67
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 67
tcuaggacac cugauucugt t 21
<210> 68
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 68
tauaaggggc ugccacaggt t 21
<210> 69
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 69
taacaauaag gggcugccat t 21
<210> 70
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 70
tguccgacua ugcuggugut t 21
<210> 71
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 71
tucucagcau cuggauucct t 21
<210> 72
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 72
tcgaaucuca gcaucuggat t 21
<210> 73
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 73
taagggcgaa ucucagcaut t 21
<210> 74
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 74
tugacacugg gauccauggt t 21
<210> 75
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 75
tccguuggug cuucuucagt t 21
<210> 76
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 76
tcuugauucu gucacuggat t 21
<210> 77
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 77
tcaccguggg aguugugagt t 21
<210> 78
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 78
tucuaggaca ccugauucut t 21
<210> 79
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 79
tagucucuag gacaccugat t 21
<210> 80
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 80
tcaauaaggg gcugccacat t 21
<210> 81
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 81
tcugcgucug agcauugugt t 21
<210> 82
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 82
tacaggaucu ggauuucggt t 21
<210> 83
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 83
tccggggguu uccucaguct t 21
<210> 84
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 84
tuguccauaa ugguaguagt t 21
<210> 85
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 85
tucuguccau aaugguagut t 21
<210> 86
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 86
tacucugucc auaaugguat t 21
<210> 87
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 87
taacucuguc cauaauggut t 21
<210> 88
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 88
tgggcgaauc ucagcaucut t 21
<210> 89
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 89
tagggcgaau cucagcauct t 21
<210> 90
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 90
taacaccaag ggcgaaucut t 21
<210> 91
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 91
taggacacuu gauucuguct t 21
<210> 92
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 92
tggaccaaga cugacaugut t 21
<210> 93
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 93
tggucaggcc accauuuggt t 21
<210> 94
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 94
tauccauggu auaacaccat t 21
<210> 95
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 95
tgggauccau gguauaacat t 21
<210> 96
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 96
tuggacauug ugucagguut t 21
<210> 97
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 97
tauucuguca cuggacauut t 21
<210> 98
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 98
tggugcuugu ucagaaacat t 21
<210> 99
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 99
tggagaauga gccucgauat t 21
<210> 100
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 100
tguggagaau gagccucgat t 21
<210> 101
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 101
tccgugggag uugugaggat t 21
<210> 102
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 102
tggaccaccg ugggaguugt t 21
<210> 103
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 103
tugcuuguuc agaaggagct t 21
<210> 104
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 104
tcugaugcca gugugguaut t 21
<210> 105
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 105
tuaggacacc ugauucugut t 21
<210> 106
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 106
tcucuaggac accugauuct t 21
<210> 107
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 107
tucucuagga caccugauut t 21
<210> 108
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 108
tgucucuagg acaccugaut t 21
<210> 109
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-26
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 109
tgagaaugag ccucgauaac ucuuau 26
<210> 110
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-26
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 110
tgacaccuga uucuguuucu gaguau 26
<210> 111
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-26
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 111
tcguauaaca auaaggggcu gccuau 26
<210> 112
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-26
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 112
tgcgucugag cauuguguca gguuau 26
<210> 113
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-26
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 113
tugcgucuga gcauuguguc agguau 26
<210> 114
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-26
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 114
taagggcgaa ucucagcauc ugguau 26
<210> 115
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 115
uuaacaauaa ggggcugc 18
<210> 116
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 116
uguauaacaa uaaggggc 18
<210> 117
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 117
ucguauaaca auaagggg 18
<210> 118
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 118
ugcgucugag cauugugu 18
<210> 119
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 119
uugcgucuga gcauugug 18
<210> 120
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 120
ucaggaucug gauuucgg 18
<210> 121
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 121
uugcaucuga gcaucgug 18
<210> 122
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 122
ucgacuaugc uggugugg 18
<210> 123
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 123
uuuucugggg uccgacua 18
<210> 124
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 124
ugcgaaucuc agcaucug 18
<210> 125
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 125
uugcaaggac acuugauu 18
<210> 126
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 126
uaaugagccu cgauaacu 18
<210> 127
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 127
ugaaugagcc ucgauaac 18
<210> 128
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 128
ugacauugug ucagguug 18
<210> 129
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 129
ugagaaugag ccucgaua 18
<210> 130
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 130
uccauuuggg uaguauuc 18
<210> 131
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 131
ucaccauuug gguaguau 18
<210> 132
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 132
ugacaccuga uucuguuu 18
<210> 133
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 133
uggacaccug auucuguu 18
<210> 134
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 134
uuaacaauaa ggggcug 17
<210> 135
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 135
uguauaacaa uaagggg 17
<210> 136
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 136
ucguauaaca auaaggg 17
<210> 137
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 137
ugcgucugag cauugug 17
<210> 138
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 138
uugcgucuga gcauugu 17
<210> 139
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 139
ucaggaucug gauuucg 17
<210> 140
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 140
uugcaucuga gcaucgu 17
<210> 141
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 141
ucgacuaugc uggugug 17
<210> 142
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 142
uuuucugggg uccgacu 17
<210> 143
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 143
ugcgaaucuc agcaucu 17
<210> 144
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 144
uugcaaggac acuugau 17
<210> 145
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 145
uaaugagccu cgauaac 17
<210> 146
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 146
ugaaugagcc ucgauaa 17
<210> 147
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 147
ugacauugug ucagguu 17
<210> 148
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 148
ugagaaugag ccucgau 17
<210> 149
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 149
uccauuuggg uaguauu 17
<210> 150
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 150
ucaccauuug gguagua 17
<210> 151
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 151
ugacaccuga uucuguu 17
<210> 152
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 152
uggacaccug auucugu 17
<210> 153
<211> 26
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 153
ugagaaugag ccucgauaac ucuuau 26
<210> 154
<211> 26
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 154
ugacaccuga uucuguuucu gaguau 26
<210> 155
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 1-22,24-26
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 155
ugagaaugag ccucgauaac uctuau 26
<210> 156
<211> 26
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 156
ucguauaaca auaaggggcu gccuau 26
<210> 157
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 157
ugagaaugag ccucgauaat t 21
<210> 158
<211> 26
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 158
ucguauaaca auaaggcgcu gccuau 26
<210> 159
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 1-16
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 159
ugagaaugag ccucgat 17
<210> 160
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 1-15
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 160
ugacaccuga uucugtt 17
<210> 161
<211> 24
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 161
ucguauaaca auaaggggcu gauu 24
<210> 162
<211> 24
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 162
ucguauaaca auaaggggcu gcuu 24
<210> 163
<211> 24
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 163
ugagaaugag ccucgauaac ucuu 24
<210> 164
<211> 21
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 164
ucguauaaca auaaggggcu u 21
<210> 165
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 165
uguauaacaa uaagggg 17
<210> 166
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 166
ucguauaaca auaaggg 17
<210> 167
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 1-16
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 167
ugagaaugag ccucgat 17
<210> 168
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 1-15
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 168
ugacaccuga uucugtt 17
<210> 169
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-26
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 169
tucguauaac aauaaggggc ugccua 26
<210> 170
<211> 26
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 170
uaucguauaa caauaagggg cugccu 26
<210> 171
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-26
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 171
tccguauaac aauaaggggc ugccua 26
<210> 172
<211> 26
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 172
cuccguauaa caauaagggg cugccu 26
<210> 173
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-26
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 173
tugagaauga gccucgauaa cucuua 26
<210> 174
<211> 26
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 174
uaugagaaug agccucgaua acucuu 26
<210> 175
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-26
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 175
tggagaauga gccucgauaa cucuua 26
<210> 176
<211> 26
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 176
guggagaaug agccucgaua acucuu 26
<210> 177
<211> 21
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 177
ugagaaugag ccucgauaau u 21
<210> 178
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-21
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 178
tcguauaaca auaaggggcu u 21
<210> 179
<211> 26
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 179
ugagaaugag ccucgauaau uauaua 26
<210> 180
<211> 23
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 180
ucguauaaca auaaggggcu gcc 23
<210> 181
<211> 24
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-24
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 181
tucguauaac aauaaggggc ugcc 24
<210> 182
<211> 22
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-22
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 182
tucguauaac aauaaggggc ug 22
<210> 183
<211> 26
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 183
ugagaaugag ccucgauaac uaucgc 26
<210> 184
<211> 26
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 184
ugagaaugag ccucgauaac uauuca 26
<210> 185
<211> 26
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 185
ugagaaugag ccucgauaac uacgau 26
<210> 186
<211> 21
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 186
ucguauaaca auaaggggcg u 21
<210> 187
<211> 24
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 187
ucguauaaca auaaggggcu gccu 24
<210> 188
<211> 21
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 188
ucguauaaca auaaggggcu g 21
<210> 189
<211> 24
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-24
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 189
tcguauaaca auaaggggcu gcuu 24
<210> 190
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 190
acgcagaagg gacugccgat 20
<210> 191
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 191
ggggugcagg agugcuacat 20
<210> 192
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 192
cuguggcagc cccuuauuat 20
<210> 193
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 193
ggcagccccu uauuguuaat 20
<210> 194
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 194
agccccuuau uguuauacat 20
<210> 195
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 195
gccccuuauu guuauacgat 20
<210> 196
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 196
ugacacaaug cucagacgat 20
<210> 197
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 197
gacacaaugc ucagacgcat 20
<210> 198
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 198
acacaaugcu cagacgcaat 20
<210> 199
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 199
acaaugcuca gacgcagaat 20
<210> 200
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 200
cugccgaaau ccagauccat 20
<210> 201
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 201
gccgaaaucc agauccugat 20
<210> 202
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 202
ugacacgaug cucagaugat 20
<210> 203
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 203
gacacgaugc ucagaugcat 20
<210> 204
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 204
acacgaugcu cagaugcaat 20
<210> 205
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 205
acgaugcuca gaugcagaat 20
<210> 206
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 206
uccaagccua gaggcuuuat 20
<210> 207
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 207
aggaaacccc cgggguacat 20
<210> 208
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 208
ggaaaccccc gggguacaat 20
<210> 209
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 209
gaaacccccg ggguacagat 20
<210> 210
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 210
ugcuacuacc auuauggaat 20
<210> 211
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 211
gcuacuacca uuauggacat 20
<210> 212
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 212
cuaccauuau ggacagagat 20
<210> 213
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 213
accacaccag cauagucgat 20
<210> 214
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 214
ccacaccagc auagucggat 20
<210> 215
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 215
cacaccagca uagucggaat 20
<210> 216
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 216
caccagcaua gucggaccat 20
<210> 217
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 217
auagucggac cccagaaaat 20
<210> 218
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 218
uagucggacc ccagaaaaat 20
<210> 219
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 219
ccagaugcug agauucgcat 20
<210> 220
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 220
gcugagauuc gcccuuggat 20
<210> 221
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 221
cugagauucg cccuugguat 20
<210> 222
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 222
ugagauucgc ccuuggugat 20
<210> 223
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 223
gagauucgcc cuugguguat 20
<210> 224
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 224
auggauccca gugucaggat 20
<210> 225
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 225
gaaucaagug uccuugcaat 20
<210> 226
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 226
aaucaagugu ccuugcaaat 20
<210> 227
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 227
gaagcaccaa cggagcaaat 20
<210> 228
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 228
gaguuaucga ggcucauuat 20
<210> 229
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 229
aguuaucgag gcucauucat 20
<210> 230
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 230
gacaacagaa uauuauccat 20
<210> 231
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 231
cuugguguua uaccauggat 20
<210> 232
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 232
gguguuauac cauggaucat 20
<210> 233
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 233
uauaccaugg aucccaauat 20
<210> 234
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 234
auaccaugga ucccaaugat 20
<210> 235
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 235
uaccauggau cccaauguat 20
<210> 236
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 236
accauggauc ccaaugucat 20
<210> 237
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 237
gcaaccugac acaaugucat 20
<210> 238
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 238
cugacacaau guccagugat 20
<210> 239
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 239
ccagugacag aaucaaguat 20
<210> 240
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 240
uuaucgaggc ucauucucat 20
<210> 241
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 241
agaauacuac ccaaauggat 20
<210> 242
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 242
aauacuaccc aaauggugat 20
<210> 243
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 243
auacuaccca aaugguggat 20
<210> 244
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 244
auucgcccuu gguguuauat 20
<210> 245
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 245
uauaccaugg aucccaguat 20
<210> 246
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 246
auaccaugga ucccagugat 20
<210> 247
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 247
cacaacuccc acggugguat 20
<210> 248
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 248
aagaacaugu cagucuugat 20
<210> 249
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 249
aguguccuca caacucccat 20
<210> 250
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 250
aacaagcacc accugagaat 20
<210> 251
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 251
ccugagaaaa gcccugugat 20
<210> 252
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 252
ugauaccaca cuggcaucat 20
<210> 253
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 253
gauaccacac uggcaucaat 20
<210> 254
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 254
gaaacagaau caggugucat 20
<210> 255
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 255
aaacagaauc agguguccat 20
<210> 256
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 256
cagaaucagg uguccuagat 20
<210> 257
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 257
ccuguggcag ccccuuauat 20
<210> 258
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 258
uggcagcccc uuauuguuat 20
<210> 259
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 259
acaccagcau agucggacat 20
<210> 260
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 260
ggaauccaga ugcugagaat 20
<210> 261
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 261
uccagaugcu gagauucgat 20
<210> 262
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 262
augcugagau ucgcccuuat 20
<210> 263
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 263
ccauggaucc cagugucaat 20
<210> 264
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 264
cugaagaagc accaacggat 20
<210> 265
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 265
uccagugaca gaaucaagat 20
<210> 266
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 266
cucacaacuc ccacggugat 20
<210> 267
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 267
agaaucaggu guccuagaat 20
<210> 268
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 268
ucaggugucc uagagacuat 20
<210> 269
<211> 23
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-22
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 269
uauagccccu uauuguuaua cat 23
<210> 270
<211> 23
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-22
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 270
uaugccccuu auuguuauac gat 23
<210> 271
<211> 23
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-22
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 271
uaugacacaa ugcucagacg cat 23
<210> 272
<211> 23
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-22
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 272
uauacacaau gcucagacgc aat 23
<210> 273
<211> 23
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-22
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 273
uauuuaucga ggcucauucu cat 23
<210> 274
<211> 23
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-22
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 274
uaugaaacag aaucaggugu cat 23
<210> 275
<211> 23
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-22
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 275
uauacaccag cauagucgga cat 23
<210> 276
<211> 23
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-22
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 276
uauuccagau gcugagauuc gat 23
<210> 277
<211> 23
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-22
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 277
uauaugcuga gauucgcccu uat 23
<210> 278
<211> 23
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-22
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 278
uauccaugga ucccaguguc aat 23
<210> 279
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 279
uguggcagcc ccuuauugat 20
<210> 280
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 280
cacaaugcuc agacgcagat 20
<210> 281
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 281
ccgaaaucca gauccuguat 20
<210> 282
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 282
gacugaggaa acccccggat 20
<210> 283
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 283
cuacuaccau uauggacaat 20
<210> 284
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 284
acuaccauua uggacagaat 20
<210> 285
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 285
uaccauuaug gacagaguat 20
<210> 286
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 286
accauuaugg acagaguuat 20
<210> 287
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 287
agaugcugag auucgcccat 20
<210> 288
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 288
gaugcugaga uucgcccuat 20
<210> 289
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 289
agauucgccc uugguguuat 20
<210> 290
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 290
gacagaauca aguguccuat 20
<210> 291
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 291
acaugucagu cuugguccat 20
<210> 292
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 292
ccaaauggug gccugaccat 20
<210> 293
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 293
ugguguuaua ccauggauat 20
<210> 294
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 294
uguuauacca uggaucccat 20
<210> 295
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 295
aaccugacac aauguccaat 20
<210> 296
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 296
aauguccagu gacagaauat 20
<210> 297
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 297
uguuucugaa caagcaccat 20
<210> 298
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 298
uaucgaggcu cauucuccat 20
<210> 299
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 299
ucgaggcuca uucuccacat 20
<210> 300
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 300
uccucacaac ucccacggat 20
<210> 301
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 301
caacucccac ggugguccat 20
<210> 302
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 302
gcuccuucug aacaagcaat 20
<210> 303
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 303
auaccacacu ggcaucagat 20
<210> 304
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 304
acagaaucag guguccuaat 20
<210> 305
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 305
gaaucaggug uccuagagat 20
<210> 306
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 306
aaucaggugu ccuagagaat 20
<210> 307
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 307
aucagguguc cuagagacat 20
<210> 308
<211> 26
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 308
uauauaguua ucgaggcuca uucuca 26
<210> 309
<211> 26
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 309
uauaucagaa acagaaucag guguca 26
<210> 310
<211> 26
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 310
uauaucagcc ccuuauuguu auacga 26
<210> 311
<211> 26
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 311
uauaucugac acaaugcuca gacgca 26
<210> 312
<211> 26
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 312
uauauugaca caaugcucag acgcaa 26
<210> 313
<211> 26
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 313
uauauagaug cugagauucg cccuua 26
<210> 314
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 314
gcagccccuu auuguuaa 18
<210> 315
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 315
gccccuuauu guuauaca 18
<210> 316
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 316
ccccuuauug uuauacga 18
<210> 317
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 317
acacaaugcu cagacgca 18
<210> 318
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 318
cacaaugcuc agacgcaa 18
<210> 319
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 319
ccgaaaucca gauccuga 18
<210> 320
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 320
cacgaugcuc agaugcaa 18
<210> 321
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 321
ccacaccagc auagucga 18
<210> 322
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 322
uagucggacc ccagaaaa 18
<210> 323
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 323
cagaugcuga gauucgca 18
<210> 324
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 324
aaucaagugu ccuugcaa 18
<210> 325
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 325
aguuaucgag gcucauua 18
<210> 326
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 326
guuaucgagg cucauuca 18
<210> 327
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 327
caaccugaca caauguca 18
<210> 328
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 328
uaucgaggcu cauucuca 18
<210> 329
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 329
gaauacuacc caaaugga 18
<210> 330
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 330
auacuaccca aaugguga 18
<210> 331
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 331
aaacagaauc agguguca 18
<210> 332
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 332
aacagaauca ggugucca 18
<210> 333
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 333
cagccccuua uuguuaa 17
<210> 334
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 334
ccccuuauug uuauaca 17
<210> 335
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 335
cccuuauugu uauacga 17
<210> 336
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 336
cacaaugcuc agacgca 17
<210> 337
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 337
acaaugcuca gacgcaa 17
<210> 338
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 338
cgaaauccag auccuga 17
<210> 339
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 339
acgaugcuca gaugcaa 17
<210> 340
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 340
cacaccagca uagucga 17
<210> 341
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 341
agucggaccc cagaaaa 17
<210> 342
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 342
agaugcugag auucgca 17
<210> 343
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 343
aucaaguguc cuugcaa 17
<210> 344
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 344
guuaucgagg cucauua 17
<210> 345
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 345
uuaucgaggc ucauuca 17
<210> 346
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 346
aaccugacac aauguca 17
<210> 347
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 347
aucgaggcuc auucuca 17
<210> 348
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 348
aauacuaccc aaaugga 17
<210> 349
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 349
uacuacccaa augguga 17
<210> 350
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 350
aacagaauca gguguca 17
<210> 351
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 351
acagaaucag gugucca 17
<210> 352
<211> 26
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 352
uauaucagcg ccuuauuguu auacga 26
<210> 353
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3-17
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 353
atcgaggcuc auucuca 17
<210> 354
<211> 24
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 354
ucagccccuu auuguuauac gauu 24
<210> 355
<211> 22
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 355
ucagccccuu auuguuauac ga 22
<210> 356
<211> 24
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 356
uaguuaucga ggcucauucu cauu 24
<210> 357
<211> 21
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 357
gccccuuauu guuauacgau u 21
<210> 358
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-25
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 358
auaucagccc cuuauuguua uacgat 26
<210> 359
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-25
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 359
uaucagcccc uuauuguuau acgaut 26
<210> 360
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-25
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 360
auauaguuau cgaggcucau ucucat 26
<210> 361
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-25
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 361
uauaguuauc gaggcucauu cucaut 26
<210> 362
<211> 21
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 362
uuaucgaggc ucauucucau u 21
<210> 363
<211> 26
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 363
uauauaauua ucgaggcuca uucuca 26
<210> 364
<211> 25
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-23
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 364
ggcagccccu uauuguuaua cgatt 25
<210> 365
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-25
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 365
ggcagccccu uauuguuaua cgauut 26
<210> 366
<211> 25
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1-21
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 366
cagccccuua uuguuauacg atttt 25
<210> 367
<211> 26
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 367
gcgauaguua ucgaggcuca uucuca 26
<210> 368
<211> 26
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 368
ugaauaguua ucgaggcuca uucuca 26
<210> 369
<211> 26
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 369
aucguaguua ucgaggcuca uucuca 26
<210> 370
<211> 26
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 370
uauaaaguua ucgaggcuca uucuca 26
<210> 371
<211> 20
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 371
agccccuuau uguuauacga 20
<210> 372
<211> 21
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 372
aagccccuua uuguuauacg a 21
<210> 373
<211> 22
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 373
gcagccccuu auuguuauac ga 22
<210> 374
<211> 26
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 374
uauauaguua ucgaggcuca uucuca 26
<210> 375
<211> 21
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 375
acgccccuua uuguuauacg a 21
<210> 376
<211> 21
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 376
gccccuuauu guuauacgau u 21
<210> 377
<211> 22
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 377
agccccuuau uguuauacga uu 22
<210> 378
<211> 23
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 378
aagccccuua uuguuauacg auu 23
<210> 379
<211> 24
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 379
uaucagcccc uuauuguuau acga 24
<210> 380
<211> 24
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 380
uagcagcccc uuauuguuau acga 24
<210> 381
<211> 22
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 381
gcagccccuu auuguuauac ga 22
<210> 382
<211> 26
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 382
auaagaguua ucgaggcuca uucuca 26
<210> 383
<211> 26
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 383
auaggcagcc ccuuauuguu auacga 26
<210> 384
<211> 21
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 384
cagccccuua uuguuauacg a 21
<210> 385
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,10,11,12,14,15,16,17,18,19,20,21,22,23,
24,25,26
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 385
uauaucagcc cctuauuguu auacga 26
<210> 386
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 386
tcggcagucc cuucugcgut t 21
<210> 387
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 387
tguagcacuc cugcacccct t 21
<210> 388
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 388
taauaagggg cugccacagt t 21
<210> 389
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 389
tuaacaauaa ggggcugcct t 21
<210> 390
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 390
tguauaacaa uaaggggcut t 21
<210> 391
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 391
tcguauaaca auaaggggct t 21
<210> 392
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 392
tcgucugagc auugugucat t 21
<210> 393
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 393
tgcgucugag cauuguguct t 21
<210> 394
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 394
tugcgucuga gcauugugut t 21
<210> 395
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 395
tucugcgucu gagcauugut t 21
<210> 396
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 396
tggaucugga uuucggcagt t 21
<210> 397
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 397
tcaggaucug gauuucggct t 21
<210> 398
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 398
tcaucugagc aucgugucat t 21
<210> 399
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 399
tgcaucugag caucguguct t 21
<210> 400
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 400
tugcaucuga gcaucgugut t 21
<210> 401
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 401
tucugcaucu gagcaucgut t 21
<210> 402
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 402
taaagccucu aggcuuggat t 21
<210> 403
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 403
tguaccccgg ggguuuccut t 21
<210> 404
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 404
tuguaccccg gggguuucct t 21
<210> 405
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 405
tcuguacccc ggggguuuct t 21
<210> 406
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 406
tuccauaaug guaguagcat t 21
<210> 407
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 407
tguccauaau gguaguagct t 21
<210> 408
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 408
tcucugucca uaaugguagt t 21
<210> 409
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 409
tcgacuaugc ugguguggut t 21
<210> 410
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 410
tccgacuaug cugguguggt t 21
<210> 411
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 411
tuccgacuau gcuggugugt t 21
<210> 412
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 412
tgguccgacu augcuggugt t 21
<210> 413
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 413
tuuucugggg uccgacuaut t 21
<210> 414
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 414
tuuuucuggg guccgacuat t 21
<210> 415
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 415
tgcgaaucuc agcaucuggt t 21
<210> 416
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 416
tccaagggcg aaucucagct t 21
<210> 417
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 417
taccaagggc gaaucucagt t 21
<210> 418
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 418
tcaccaaggg cgaaucucat t 21
<210> 419
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 419
tacaccaagg gcgaaucuct t 21
<210> 420
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 420
tccugacacu gggauccaut t 21
<210> 421
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 421
tugcaaggac acuugauuct t 21
<210> 422
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 422
tuugcaagga cacuugauut t 21
<210> 423
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 423
tuugcuccgu uggugcuuct t 21
<210> 424
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 424
taaugagccu cgauaacuct t 21
<210> 425
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 425
tgaaugagcc ucgauaacut t 21
<210> 426
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 426
tggauaauau ucuguuguct t 21
<210> 427
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 427
tccaugguau aacaccaagt t 21
<210> 428
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 428
tgauccaugg uauaacacct t 21
<210> 429
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 429
tauugggauc caugguauat t 21
<210> 430
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 430
tcauugggau ccaugguaut t 21
<210> 431
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 431
tacauuggga uccaugguat t 21
<210> 432
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 432
tgacauuggg auccauggut t 21
<210> 433
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 433
tgacauugug ucagguugct t 21
<210> 434
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 434
tcacuggaca uugugucagt t 21
<210> 435
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 435
tacuugauuc ugucacuggt t 21
<210> 436
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 436
tgagaaugag ccucgauaat t 21
<210> 437
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 437
tccauuuggg uaguauucut t 21
<210> 438
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 438
tcaccauuug gguaguauut t 21
<210> 439
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 439
tccaccauuu ggguaguaut t 21
<210> 440
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 440
tauaacacca agggcgaaut t 21
<210> 441
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 441
tacugggauc caugguauat t 21
<210> 442
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 442
tcacugggau ccaugguaut t 21
<210> 443
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 443
taccaccgug ggaguugugt t 21
<210> 444
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 444
tcaagacuga cauguucuut t 21
<210> 445
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 445
tgggaguugu gaggacacut t 21
<210> 446
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 446
tucucaggug gugcuuguut t 21
<210> 447
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 447
tcacagggcu uuucucaggt t 21
<210> 448
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 448
tgaugccagu gugguaucat t 21
<210> 449
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 449
tugaugccag ugugguauct t 21
<210> 450
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 450
tgacaccuga uucuguuuct t 21
<210> 451
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 451
tggacaccug auucuguuut t 21
<210> 452
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 452
tcuaggacac cugauucugt t 21
<210> 453
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 453
tauaaggggc ugccacaggt t 21
<210> 454
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 454
taacaauaag gggcugccat t 21
<210> 455
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 455
tguccgacua ugcuggugut t 21
<210> 456
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 456
tucucagcau cuggauucct t 21
<210> 457
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 457
tcgaaucuca gcaucuggat t 21
<210> 458
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 458
taagggcgaa ucucagcaut t 21
<210> 459
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 459
tugacacugg gauccauggt t 21
<210> 460
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 460
tccguuggug cuucuucagt t 21
<210> 461
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 461
tcuugauucu gucacuggat t 21
<210> 462
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 462
tcaccguggg aguugugagt t 21
<210> 463
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 463
tucuaggaca ccugauucut t 21
<210> 464
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 464
tagucucuag gacaccugat t 21
<210> 465
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 465
tguauaacaa uaaggggcut t 21
<210> 466
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 6
<223> /mod_base = "2'-3' seco nucleoside"
<220>
<221> modified_base
<222> 2,4,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 466
tguauaacaa uaaggggcut t 21
<210> 467
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 7
<223> /mod_base = "2'-3' seco nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 467
tguauaacaa uaaggggcut t 21
<210> 468
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 468
tcguauaaca auaaggggct t 21
<210> 469
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 6
<223> /mod_base = "2'-3' seco nucleoside"
<220>
<221> modified_base
<222> 2,4,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 469
tcguauaaca auaaggggct t 21
<210> 470
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 7
<223> /mod_base = "2'-3' seco nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 470
tcguauaaca auaaggggct t 21
<210> 471
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 471
tgcgucugag cauuguguct t 21
<210> 472
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 6
<223> /mod_base = "2'-3' seco nucleoside"
<220>
<221> modified_base
<222> 2,4,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 472
tgcgucugag cauuguguct t 21
<210> 473
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 7
<223> /mod_base = "2'-3' seco nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 473
tgcgucugag cauuguguct t 21
<210> 474
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 474
tugcgucuga gcauugugut t 21
<210> 475
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 6
<223> /mod_base = "2'-3' seco nucleoside"
<220>
<221> modified_base
<222> 2,4,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 475
tugcgucuga gcauugugut t 21
<210> 476
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 7
<223> /mod_base = "2'-3' seco nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 476
tugcgucuga gcauugugut t 21
<210> 477
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 477
tgagaaugag ccucgauaat t 21
<210> 478
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 6
<223> /mod_base = "2'-3' seco nucleoside"
<220>
<221> modified_base
<222> 2,4,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 478
tgagaaugag ccucgauaat t 21
<210> 479
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 7
<223> /mod_base = "2'-3' seco nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 479
tgagaaugag ccucgauaat t 21
<210> 480
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 480
tgacaccuga uucuguuuct t 21
<210> 481
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 6
<223> /mod_base = "2'-3' seco nucleoside"
<220>
<221> modified_base
<222> 2,4,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 481
tgacaccuga uucuguuuct t 21
<210> 482
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 7
<223> /mod_base = "2'-3' seco nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 482
tgacaccuga uucuguuuct t 21
<210> 483
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 483
tguccgacua ugcuggugut t 21
<210> 484
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 6
<223> /mod_base = "2'-3' seco nucleoside"
<220>
<221> modified_base
<222> 2,4,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 484
tguccgacua ugcuggugut t 21
<210> 485
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 7
<223> /mod_base = "2'-3' seco nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 485
tguccgacua ugcuggugut t 21
<210> 486
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 486
tcgaaucuca gcaucuggat t 21
<210> 487
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 6
<223> /mod_base = "2'-3' seco nucleoside"
<220>
<221> modified_base
<222> 2,4,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 487
tcgaaucuca gcaucuggat t 21
<210> 488
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 7
<223> /mod_base = "2'-3' seco nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 488
tcgaaucuca gcaucuggat t 21
<210> 489
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 489
taagggcgaa ucucagcaut t 21
<210> 490
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 6
<223> /mod_base = "2'-3' seco nucleoside"
<220>
<221> modified_base
<222> 2,4,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 490
taagggcgaa ucucagcaut t 21
<210> 491
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 7
<223> /mod_base = "2'-3' seco nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 491
taagggcgaa ucucagcaut t 21
<210> 492
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 492
tugacacugg gauccauggt t 21
<210> 493
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 6
<223> /mod_base = "2'-3' seco nucleoside"
<220>
<221> modified_base
<222> 2,4,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 493
tugacacugg gauccauggt t 21
<210> 494
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 7
<223> /mod_base = "2'-3' seco nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 494
tugacacugg gauccauggt t 21
<210> 495
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 495
tcaauaaggg gcugccacat t 21
<210> 496
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 496
tcugcgucug agcauugugt t 21
<210> 497
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 497
tacaggaucu ggauuucggt t 21
<210> 498
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 498
tccggggguu uccucaguct t 21
<210> 499
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 499
tuguccauaa ugguaguagt t 21
<210> 500
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 500
tucuguccau aaugguagut t 21
<210> 501
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 501
tacucugucc auaaugguat t 21
<210> 502
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 502
taacucuguc cauaauggut t 21
<210> 503
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 503
tgggcgaauc ucagcaucut t 21
<210> 504
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 504
tagggcgaau cucagcauct t 21
<210> 505
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 505
taacaccaag ggcgaaucut t 21
<210> 506
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 506
taggacacuu gauucuguct t 21
<210> 507
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 507
tggaccaaga cugacaugut t 21
<210> 508
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 508
tggucaggcc accauuuggt t 21
<210> 509
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 509
tauccauggu auaacaccat t 21
<210> 510
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 510
tgggauccau gguauaacat t 21
<210> 511
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 511
tuggacauug ugucagguut t 21
<210> 512
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 512
tauucuguca cuggacauut t 21
<210> 513
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 513
tggugcuugu ucagaaacat t 21
<210> 514
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 514
tggagaauga gccucgauat t 21
<210> 515
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 515
tguggagaau gagccucgat t 21
<210> 516
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 516
tccgugggag uugugaggat t 21
<210> 517
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 517
tggaccaccg ugggaguugt t 21
<210> 518
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 518
tugcuuguuc agaaggagct t 21
<210> 519
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 519
tcugaugcca gugugguaut t 21
<210> 520
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 520
tuaggacacc ugauucugut t 21
<210> 521
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 521
tcucuaggac accugauuct t 21
<210> 522
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 522
tucucuagga caccugauut t 21
<210> 523
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 523
tgucucuagg acaccugaut t 21
<210> 524
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 524
tgagaaugag ccucgauaac ucuuau 26
<210> 525
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,13,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 525
tgagaaugag ccucgauaac ucuuau 26
<210> 526
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,13,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,14,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 526
tgagaaugag ccucgauaac ucuuau 26
<210> 527
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,13,15,17,19,21,23
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,14,16,18,20,22,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 527
tgagaaugag ccucgauaac ucuuau 26
<210> 528
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 528
tgacaccuga uucuguuucu gaguau 26
<210> 529
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,13,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 529
tgacaccuga uucuguuucu gaguau 26
<210> 530
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,13,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,14,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 530
tgacaccuga uucuguuucu gaguau 26
<210> 531
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,13,15,17,19,21,23
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,14,16,18,20,22,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 531
tgacaccuga uucuguuucu gaguau 26
<210> 532
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 532
tcguauaaca auaaggggcu gccuau 26
<210> 533
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 533
tgcgucugag cauuguguca gguuau 26
<210> 534
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 534
tugcgucuga gcauuguguc agguau 26
<210> 535
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 535
tgagaaugag ccucgauaac ucuuau 26
<210> 536
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 536
tgacaccuga uucuguuucu gaguau 26
<210> 537
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 537
taagggcgaa ucucagcauc ugguau 26
<210> 538
<211> 18
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 538
uuaacaauaa ggggcugc 18
<210> 539
<211> 18
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 539
uguauaacaa uaaggggc 18
<210> 540
<211> 18
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 540
ucguauaaca auaagggg 18
<210> 541
<211> 18
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 541
ugcgucugag cauugugu 18
<210> 542
<211> 18
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 542
uugcgucuga gcauugug 18
<210> 543
<211> 18
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 543
ucaggaucug gauuucgg 18
<210> 544
<211> 18
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 544
uugcaucuga gcaucgug 18
<210> 545
<211> 18
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 545
ucgacuaugc uggugugg 18
<210> 546
<211> 18
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 546
uuuucugggg uccgacua 18
<210> 547
<211> 18
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 547
ugcgaaucuc agcaucug 18
<210> 548
<211> 18
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 548
uugcaaggac acuugauu 18
<210> 549
<211> 18
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 549
uaaugagccu cgauaacu 18
<210> 550
<211> 18
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 550
ugaaugagcc ucgauaac 18
<210> 551
<211> 18
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 551
ugacauugug ucagguug 18
<210> 552
<211> 18
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 552
ugagaaugag ccucgaua 18
<210> 553
<211> 18
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 553
uccauuuggg uaguauuc 18
<210> 554
<211> 18
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 554
ucaccauuug gguaguau 18
<210> 555
<211> 18
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 555
ugacaccuga uucuguuu 18
<210> 556
<211> 18
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 556
uggacaccug auucuguu 18
<210> 557
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 557
uuaacaauaa ggggcug 17
<210> 558
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 558
uguauaacaa uaagggg 17
<210> 559
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 559
ucguauaaca auaaggg 17
<210> 560
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 560
ugcgucugag cauugug 17
<210> 561
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 561
uugcgucuga gcauugu 17
<210> 562
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 562
ucaggaucug gauuucg 17
<210> 563
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 563
uugcaucuga gcaucgu 17
<210> 564
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 564
ucgacuaugc uggugug 17
<210> 565
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 565
uuuucugggg uccgacu 17
<210> 566
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 566
ugcgaaucuc agcaucu 17
<210> 567
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 567
uugcaaggac acuugau 17
<210> 568
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 568
uaaugagccu cgauaac 17
<210> 569
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 569
ugaaugagcc ucgauaa 17
<210> 570
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 570
ugacauugug ucagguu 17
<210> 571
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 571
ugagaaugag ccucgau 17
<210> 572
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 572
uccauuuggg uaguauu 17
<210> 573
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 573
ucaccauuug gguagua 17
<210> 574
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 574
ugacaccuga uucuguu 17
<210> 575
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 575
uggacaccug auucugu 17
<210> 576
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 576
ugagaaugag ccucgauaac ucuuau 26
<210> 577
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 4,6,8,10,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,5,7,9,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 577
ugagaaugag ccucgauaac ucuuau 26
<210> 578
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 4,6,8,10,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,5,7,9,11,12,13,15,17,19,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 578
ugagaaugag ccucgauaac ucuuau 26
<210> 579
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,12,13,15,17,19,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 579
ugagaaugag ccucgauaac ucuuau 26
<210> 580
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 580
ugacaccuga uucuguuucu gaguau 26
<210> 581
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 4,6,8,10,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,5,7,9,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 581
ugacaccuga uucuguuucu gaguau 26
<210> 582
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 4,6,8,10,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,5,7,9,11,12,13,15,17,19,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 582
ugacaccuga uucuguuucu gaguau 26
<210> 583
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,12,13,15,17,19,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 583
ugacaccuga uucuguuucu gaguau 26
<210> 584
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 6,10,14,16,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,7,8,9,11,12,13,15,17,18,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 584
ugagaaugag ccucgauaac ucuuau 26
<210> 585
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 8,14,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,9,10,11,12,13,15,16,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 585
ugagaaugag ccucgauaac ucuuau 26
<210> 586
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 8,14,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,9,10,11,12,13,15,16,17,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 586
ugagaaugag ccucgauaac ucuuau 26
<210> 587
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 4,6,8,10,14,16,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,5,7,9,11,12,13,15,17,18,19,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 587
ugacaccuga uucuguuucu gaguau 26
<210> 588
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 4,6,8,10,14,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,5,7,9,11,12,13,15,16,17,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 588
ugacaccuga uucuguuucu gaguau 26
<210> 589
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 10,14,16,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,11,12,13,15,17,18,19,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 589
ugacaccuga uucuguuucu gaguau 26
<210> 590
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,3,5,7,8,10,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,4,6,9,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 590
ugacaccuga uucuguuucu gaguau 26
<210> 591
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,3,5,8,10,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,4,6,7,9,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 591
ugacaccuga uucuguuucu gaguau 26
<210> 592
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,7,8,10,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,9,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 592
ugacaccuga uucuguuucu gaguau 26
<210> 593
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,8,9,10,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 593
tgacaccuga uucuguuucu gaguau 26
<210> 594
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,10,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 594
ugacaccuga uucuguuucu gaguau 26
<210> 595
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,8,9,10,11,12,13,15,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 595
tgacaccuga uucuguuucu gaguau 26
<210> 596
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,10,11,12,13,15,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 596
ugacaccuga uucuguuucu gaguau 26
<210> 597
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 597
tgacaccuga uucuguuucu gaguau 26
<210> 598
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,12,13,15,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 598
ugacaccuga uucuguuucu gaguau 26
<210> 599
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 599
ucguauaaca auaaggggcu gccuau 26
<210> 600
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,12,13,15,17,19,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 600
ucguauaaca auaaggggcu gccuau 26
<210> 601
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,12,13,15,17,19,21,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 22,23
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 601
ugagaaugag ccucgauaac uctuau 26
<210> 602
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,12,13,15,17,19,21,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 22,23
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 602
ugagaaugag ccucgauaac uctuau 26
<210> 603
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,12,13,15,17,19,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 603
ugagaaugag ccucgauaac ucuuau 26
<210> 604
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,9,10,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 604
ucguauaaca auaaggggcu gccuau 26
<210> 605
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,9,10,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,11,12,13,15,17,19,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 605
ucguauaaca auaaggggcu gccuau 26
<210> 606
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,11,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 606
ugagaaugag ccucgauaac ucuuau 26
<210> 607
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,11,12,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 607
ugagaaugag ccucgauaac ucuuau 26
<210> 608
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,6,10,14,16,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,7,8,9,11,12,13,15,17,18,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 608
ugagaaugag ccucgauaac ucuuau 26
<210> 609
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,8,14,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,9,10,11,12,13,15,16,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 609
ugagaaugag ccucgauaac ucuuau 26
<210> 610
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,8,14,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,9,10,11,12,13,15,16,17,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 610
ugagaaugag ccucgauaac ucuuau 26
<210> 611
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,10,14,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,12,13,15,16,17,18,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 611
ugagaaugag ccucgauaac ucuuau 26
<210> 612
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,14,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,8,9,10,11,12,13,15,16,17,18,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 612
ugagaaugag ccucgauaac ucuuau 26
<210> 613
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,14,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,8,9,10,11,12,13,15,16,17,18,19,20,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 613
ugagaaugag ccucgauaac ucuuau 26
<210> 614
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,14,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,8,9,10,11,12,13,15,16,17,18,19,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 614
ugagaaugag ccucgauaac ucuuau 26
<210> 615
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,8,9,10,11,12,13,15,16,17,18,19,20,21,22,23,24,
26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 615
ugagaaugag ccucgauaac ucuuau 26
<210> 616
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,10,13,14,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,12,15,16,17,18,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 616
ugagaaugag ccucgauaac ucuuau 26
<210> 617
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,13,14,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,8,9,10,11,12,15,16,17,18,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 617
ugagaaugag ccucgauaac ucuuau 26
<210> 618
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,13,14,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,8,9,10,11,12,15,16,17,18,19,20,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 618
ugagaaugag ccucgauaac ucuuau 26
<210> 619
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,13,14,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,8,9,10,11,12,15,16,17,18,19,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 619
ugagaaugag ccucgauaac ucuuau 26
<210> 620
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,13,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,8,9,10,11,12,15,16,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 620
ugagaaugag ccucgauaac ucuuau 26
<210> 621
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,10,12,14,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,16,17,18,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 621
ugagaaugag ccucgauaac ucuuau 26
<210> 622
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,12,14,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,8,9,10,11,13,15,16,17,18,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 622
ugagaaugag ccucgauaac ucuuau 26
<210> 623
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,12,14,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,8,9,10,11,13,15,16,17,18,19,20,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 623
ugagaaugag ccucgauaac ucuuau 26
<210> 624
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,12,14,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,8,9,10,11,13,15,16,17,18,19,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 624
ugagaaugag ccucgauaac ucuuau 26
<210> 625
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,12,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,8,9,10,11,13,15,16,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 625
ugagaaugag ccucgauaac ucuuau 26
<210> 626
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,10,11,14,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,12,13,15,16,17,18,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 626
ugagaaugag ccucgauaac ucuuau 26
<210> 627
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,11,14,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,8,9,10,12,13,15,16,17,18,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 627
ugagaaugag ccucgauaac ucuuau 26
<210> 628
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,11,14,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,8,9,10,12,13,15,16,17,18,19,20,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 628
ugagaaugag ccucgauaac ucuuau 26
<210> 629
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,11,14,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,8,9,10,12,13,15,16,17,18,19,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 629
ugagaaugag ccucgauaac ucuuau 26
<210> 630
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,11,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,8,9,10,12,13,15,16,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 630
ugagaaugag ccucgauaac ucuuau 26
<210> 631
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,10,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 631
ucguauaaca auaaggggcu gccuau 26
<210> 632
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,12,13,15,16,17,18,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 632
ucguauaaca auaaggggcu gccuau 26
<210> 633
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,8,10,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,9,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 633
ucguauaaca auaaggggcu gccuau 26
<210> 634
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,12,13,15,17,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 634
ucguauaaca auaaggggcu gccuau 26
<210> 635
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,10,11,12,13,15,17,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 635
ucguauaaca auaaggggcu gccuau 26
<210> 636
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,8,10,14,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,9,11,12,13,15,16,17,18,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 636
ucguauaaca auaaggggcu gccuau 26
<210> 637
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,12,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,10,11,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 637
ucguauaaca auaaggggcu gccuau 26
<210> 638
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,8,10,12,14,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,9,11,13,15,16,17,18,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 638
ucguauaaca auaaggggcu gccuau 26
<210> 639
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3,20,21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 639
ugagaaugag ccucgauaat t 21
<210> 640
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,8,10,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,9,11,12,13,15,16,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 640
ucguauaaca auaaggggcu gccuau 26
<210> 641
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,8,9,10,11,12,13,15,16,17,18,19,20,21,22,23,24,
26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 641
ucguauaaca auaaggggcu gccuau 26
<210> 642
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,8,10,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,9,11,12,13,15,16,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 642
ugagaaugag ccucgauaac ucuuau 26
<210> 643
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 643
tgagaaugag ccucgauaac ucuuau 26
<210> 644
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end Vinyl Phosphonate modification"
<400> 644
tgagaaugag ccucgauaac ucuuau 26
<210> 645
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end Vinyl Phosphonate modification"
<400> 645
tgagaaugag ccucgauaac ucuuau 26
<210> 646
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 646
tgagaaugag ccucgauaac ucuuau 26
<210> 647
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end Vinyl Phosphonate modification"
<400> 647
tcguauaaca auaaggggcu gccuau 26
<210> 648
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end Vinyl Phosphonate modification"
<400> 648
tcguauaaca auaaggggcu gccuau 26
<210> 649
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,3,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,4,5,6,7,8,9,10,11,12,13,15,16,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 649
ugagaaugag ccucgauaac ucuuau 26
<210> 650
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,7,8,9,10,11,12,13,15,16,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 650
ugagaaugag ccucgauaac ucuuau 26
<210> 651
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,5,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,6,7,8,9,10,11,12,13,15,16,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 651
ugagaaugag ccucgauaac ucuuau 26
<210> 652
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,6,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,7,8,9,10,11,12,13,15,16,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 652
ugagaaugag ccucgauaac ucuuau 26
<210> 653
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,7,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,8,9,10,11,12,13,15,16,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 653
ugagaaugag ccucgauaac ucuuau 26
<210> 654
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,8,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,9,10,11,12,13,15,16,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 654
ugagaaugag ccucgauaac ucuuau 26
<210> 655
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,10,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,8,9,11,12,13,15,16,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 655
ugagaaugag ccucgauaac ucuuau 26
<210> 656
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 656
ucguauaaca auaaggcgcu gccuau 26
<210> 657
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,19,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,12,13,15,16,17,18,20,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 657
ucguauaaca auaaggggcu gccuau 26
<210> 658
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,12,13,15,16,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 658
ucguauaaca auaaggggcu gccuau 26
<210> 659
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,3,8,10,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,4,5,6,7,9,11,12,13,15,16,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 659
ucguauaaca auaaggggcu gccuau 26
<210> 660
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,10,11,12,13,15,16,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 660
ucguauaaca auaaggggcu gccuau 26
<210> 661
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,9,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,10,11,12,13,15,16,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 661
ucguauaaca auaaggggcu gccuau 26
<210> 662
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,3,7,9,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,4,5,6,8,10,11,12,13,15,16,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 662
ucguauaaca auaaggggcu gccuau 26
<210> 663
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,12,13,15,16,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 663
ugagaaugag ccucgauaac ucuuau 26
<210> 664
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,3,6,8,10,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,4,5,7,9,11,12,13,15,16,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 664
ugagaaugag ccucgauaac ucuuau 26
<210> 665
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,3,5,8,10,12,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,4,6,7,9,11,13,15,16,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 665
ugagaaugag ccucgauaac ucuuau 26
<210> 666
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,3,5,8,11,12,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,4,6,7,9,10,13,15,16,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 666
ugagaaugag ccucgauaac ucuuau 26
<210> 667
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,10,11,12,13,15,16,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 667
ugagaaugag ccucgauaac ucuuau 26
<210> 668
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,8,10,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,9,11,12,13,15,16,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 668
uguauaacaa uaagggg 17
<210> 669
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 16,17
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 669
uguauaacaa uaagggg 17
<210> 670
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,8,10,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,9,11,12,13,15,16,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 670
ucguauaaca auaaggg 17
<210> 671
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 16,17
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 671
ucguauaaca auaaggg 17
<210> 672
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,8,10,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,9,11,12,13,15,16,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 672
ugagaaugag ccucgau 17
<210> 673
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,12,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,8,9,10,11,13,15,16,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 673
ugagaaugag ccucgau 17
<210> 674
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 16,17
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 674
ugagaaugag ccucgat 17
<210> 675
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,8,10,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,9,11,12,13,15,16,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 675
ugacaccuga uucuguu 17
<210> 676
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,10,11,12,13,15,16,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 676
ugacaccuga uucuguu 17
<210> 677
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 16,17
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 677
ugacaccuga uucugtt 17
<210> 678
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 4,6,8,9,10,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,11,12,13,15,17,19,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 2
<223> /mod_base = "2'-F-Arabino nucleoside"
<400> 678
ucguauaaca auaaggggcu gccuau 26
<210> 679
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,6,8,9,10,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,11,12,13,15,17,19,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 4
<223> /mod_base = "2'-F-Arabino nucleoside"
<400> 679
ucguauaaca auaaggggcu gccuau 26
<210> 680
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,8,9,10,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,11,12,13,15,17,19,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 6
<223> /mod_base = "2'-F-Arabino nucleoside"
<400> 680
ucguauaaca auaaggggcu gccuau 26
<210> 681
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,9,10,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,11,12,13,15,17,19,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 8
<223> /mod_base = "2'-F-Arabino nucleoside"
<400> 681
ucguauaaca auaaggggcu gccuau 26
<210> 682
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 8,10,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,9,11,12,13,15,16,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 2
<223> /mod_base = "2'-F-Arabino nucleoside"
<400> 682
ugagaaugag ccucgauaac ucuuau 26
<210> 683
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,10,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,9,11,12,13,15,16,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 8
<223> /mod_base = "2'-F-Arabino nucleoside"
<400> 683
ugagaaugag ccucgauaac ucuuau 26
<210> 684
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,8,10,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,4,5,6,7,9,11,12,13,15,16,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 684
tgagaaugag ccucgauaac ucuuau 26
<210> 685
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,9,10,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,11,12,13,15,17,19,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 685
tcguauaaca auaaggggcu gccuau 26
<210> 686
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,4,5,6,7,8,9,10,11,12,13,15,16,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 686
tgagaaugag ccucgauaac ucuuau 26
<210> 687
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,10,11,12,13,15,16,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 687
ucguauaaca auaaggggcu gccuau 26
<210> 688
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,8,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,7,9,10,11,12,13,15,16,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 688
ucguauaaca auaaggggcu gccuau 26
<210> 689
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,10,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,7,8,9,11,12,13,15,16,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 689
ucguauaaca auaaggggcu gccuau 26
<210> 690
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,12,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,7,8,9,10,11,13,15,16,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 690
ucguauaaca auaaggggcu gccuau 26
<210> 691
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,6,8,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,7,9,10,11,12,13,15,16,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 691
ucguauaaca auaaggggcu gccuau 26
<210> 692
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,6,10,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,7,8,9,11,12,13,15,16,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 692
ucguauaaca auaaggggcu gccuau 26
<210> 693
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,6,12,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,7,8,9,10,11,13,15,16,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 693
ucguauaaca auaaggggcu gccuau 26
<210> 694
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,8,12,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,9,10,11,13,15,16,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 694
ucguauaaca auaaggggcu gccuau 26
<210> 695
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,10,12,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,8,9,11,13,15,16,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 695
ucguauaaca auaaggggcu gccuau 26
<210> 696
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,16,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 696
ucguauaaca auaaggggcu gccuau 26
<210> 697
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,18,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 697
ucguauaaca auaaggggcu gccuau 26
<210> 698
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19,20,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 698
ucguauaaca auaaggggcu gccuau 26
<210> 699
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 699
ucguauaaca auaaggggcu gccuau 26
<210> 700
<211> 24
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,9,10,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,11,12,13,15,17,19,21,22,23,24
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3,4,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end Vinyl Phosphonate modification"
<400> 700
ucguauaaca auaaggggcu gauu 24
<210> 701
<211> 24
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,9,10,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,11,12,13,15,17,19,21,22,23,24
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3,4,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end Vinyl Phosphonate modification"
<400> 701
ucguauaaca auaaggggcu gcuu 24
<210> 702
<211> 24
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,8,10,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,9,11,12,13,15,16,17,18,19,20,21,22,23,24
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3,4,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end Vinyl Phosphonate modification"
<400> 702
ugagaaugag ccucgauaac ucuu 24
<210> 703
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,6,8,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,7,9,10,11,12,13,15,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 703
ucguauaaca auaaggggcu gccuau 26
<210> 704
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,6,8,9,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,7,10,11,12,13,15,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 704
ucguauaaca auaaggggcu gccuau 26
<210> 705
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,6,8,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,7,9,10,11,12,13,15,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 705
ugagaaugag ccucgauaac ucuuau 26
<210> 706
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,6,8,9,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,7,10,11,12,13,15,17,18,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 706
ugagaaugag ccucgauaac ucuuau 26
<210> 707
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,9,10,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,11,12,13,15,17,19,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end Vinyl Phosphonate modification"
<400> 707
ucguauaaca auaaggggcu gccuau 26
<210> 708
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,9,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,11,12,13,15,17,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3,4,21
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end Vinyl Phosphonate modification"
<400> 708
ucguauaaca auaaggggcu u 21
<210> 709
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,9,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,11,12,13,15,17,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3,4,21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 709
ucguauaaca auaaggggcu u 21
<210> 710
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 1
<223> /mod_base = "2'-3' seco nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,9,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,11,12,13,15,17,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3,4,21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 710
ucguauaaca auaaggggcu u 21
<210> 711
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,12,13,15,17,19,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 711
ugagaaugag ccucgauaac ucuuau 26
<210> 712
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,8,10,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,9,11,12,13,15,16,17,18,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 712
ugagaaugag ccucgauaac ucuuau 26
<210> 713
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,9,10,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,11,12,13,15,17,19,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 713
ugagaaugag ccucgauaac ucuuau 26
<210> 714
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,8,9,10,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,11,12,13,15,16,17,18,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 714
ugagaaugag ccucgauaac ucuuau 26
<210> 715
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,9,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,10,11,12,13,15,17,19,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 715
ugagaaugag ccucgauaac ucuuau 26
<210> 716
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,8,9,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,10,11,12,13,15,16,17,18,19,20,21,22,23,24,25,
26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 716
ugagaaugag ccucgauaac ucuuau 26
<210> 717
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,8,10,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,9,11,12,13,15,16,17,18,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (Dy540) modification"
<400> 717
ugagaaugag ccucgauaac ucuuau 26
<210> 718
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,9,12,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,10,11,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 718
ucguauaaca auaaggggcu gccuau 26
<210> 719
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,8,12,14,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,9,10,11,13,15,16,17,18,19,20,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 719
ucguauaaca auaaggggcu gccuau 26
<210> 720
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,9,12,14,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,8,10,11,13,15,16,17,18,19,20,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 720
ucguauaaca auaaggggcu gccuau 26
<210> 721
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,9,12,14,19,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,8,10,11,13,15,16,17,18,20,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 721
ucguauaaca auaaggggcu gccuau 26
<210> 722
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,6,9,12,14,19,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,7,8,10,11,13,15,16,17,18,20,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 722
ucguauaaca auaaggggcu gccuau 26
<210> 723
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 16,17
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 723
uguauaacaa uaagggg 17
<210> 724
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 16,17
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "3' end (Sp18)s(PAZ) modification"
<400> 724
uguauaacaa uaagggg 17
<210> 725
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 16,17
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "3' end (C12)s(PAZ) modification"
<400> 725
uguauaacaa uaagggg 17
<210> 726
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 16,17
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 726
ucguauaaca auaaggg 17
<210> 727
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 16,17
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "3' end (Sp18)s(PAZ) modification"
<400> 727
ucguauaaca auaaggg 17
<210> 728
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 16,17
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "3' end (C12)s(PAZ) modification"
<400> 728
ucguauaaca auaaggg 17
<210> 729
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 16,17
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 729
ugagaaugag ccucgat 17
<210> 730
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 16,17
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "3' end (Sp18)s(PAZ) modification"
<400> 730
ugagaaugag ccucgac 17
<210> 731
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 16,17
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "3' end (C12)s(PAZ) modification"
<400> 731
ugagaaugag ccucgac 17
<210> 732
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 16,17
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 732
ugacaccuga uucugtt 17
<210> 733
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 16,17
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "3' end (Sp18)s(PAZ) modification"
<400> 733
ugacaccuga uucugtc 17
<210> 734
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 16,17
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "3' end (C12)s(PAZ) modification"
<400> 734
ugacaccuga uucugtc 17
<210> 735
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 3,5,7,13,15,17,19,21,23
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,9,10,11,12,14,16,18,20,22,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 3,4,24,25
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 735
tucguauaac aauaaggggc ugccua 26
<210> 736
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 4,6,8,14,16,18,20,22,24
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,10,11,12,13,15,17,19,21,23,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 4,5,25,26
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 736
uaucguauaa caauaagggg cugccu 26
<210> 737
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 3,5,7,13,15,17,19,21,23
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,9,10,11,12,14,16,18,20,22,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 3,4,24,25
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 737
tccguauaac aauaaggggc ugccua 26
<210> 738
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 4,6,8,14,16,18,20,22,24
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,10,11,12,13,15,17,19,21,23,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 4,5,25,26
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 738
cuccguauaa caauaagggg cugccu 26
<210> 739
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 3,5,7,9,11,15,17,19,21
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,13,14,16,18,20,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 3,4,24,25
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 739
tugagaauga gccucgauaa cucuua 26
<210> 740
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 4,6,8,10,12,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,14,15,17,19,21,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 4,5,25,26
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 740
uaugagaaug agccucgaua acucuu 26
<210> 741
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 3,5,7,9,11,15,17,19,21
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,13,14,16,18,20,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 3,4,24,25
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 741
tggagaauga gccucgauaa cucuua 26
<210> 742
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 4,6,8,10,12,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,14,15,17,19,21,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 4,5,25,26
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 742
guggagaaug agccucgaua acucuu 26
<210> 743
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 3,9,11,15
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,5,6,7,8,10,12,13,14,16,17,18,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 3,4,24,25
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 743
tugagaauga gccucgauaa cucuua 26
<210> 744
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 4,10,12,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,7,8,9,11,13,14,15,17,18,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 4,5,25,26
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 744
uaugagaaug agccucgaua acucuu 26
<210> 745
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 3,9,11,15
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,5,6,7,8,10,12,13,14,16,17,18,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 3,4,24,25
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 745
tggagaauga gccucgauaa cucuua 26
<210> 746
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 4,10,12,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,7,8,9,11,13,14,15,17,18,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 4,5,25,26
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 746
guggagaaug agccucgaua acucuu 26
<210> 747
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,10,11,13,15,17,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3,4,21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 747
ucguauaaca auaaggggcu u 21
<210> 748
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,12,13,15,17,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3,4,21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 748
ugagaaugag ccucgauaau u 21
<210> 749
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 16,17
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "3' end s(C12)s(PAZ) modification"
<400> 749
uguauaacaa uaagggg 17
<210> 750
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 16,17
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "3' end s(C12)s(PAZ) modification"
<400> 750
ucguauaaca auaaggg 17
<210> 751
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 16,17
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "3' end s(C12)s(PAZ) modification"
<400> 751
ugagaaugag ccucgac 17
<210> 752
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 16,17
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "3' end s(C12)s(PAZ) modification"
<400> 752
ugacaccuga uucugtc 17
<210> 753
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,9,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,11,12,13,15,17,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 2,3,4,21
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end cyclopropyl phosphonate modification"
<400> 753
tcguauaaca auaaggggcu u 21
<210> 754
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,12,13,15,17,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 22,23,24,25,26
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,4,21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 754
ugagaaugag ccucgauaau uauaua 26
<210> 755
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,12,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,10,11,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,22,23
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 755
ucguauaaca auaaggggcu gccuau 26
<210> 756
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,12,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,10,11,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,22
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 756
ucguauaaca auaaggggcu gccuau 26
<210> 757
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,12,13,15,17,19,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,22,23
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 757
ugagaaugag ccucgauaac ucuuau 26
<210> 758
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,12,13,15,17,19,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,22
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 758
ugagaaugag ccucgauaac ucuuau 26
<210> 759
<211> 24
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,9,10,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,11,12,13,15,17,19,21,22,23,24
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3,4,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 759
ucguauaaca auaaggggcu gcuu 24
<210> 760
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,9,10,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,11,12,13,14,15,17,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3,4,21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 760
ucguauaaca auaaggggcu u 21
<210> 761
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,9,10,12,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,11,13,14,15,17,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3,4,21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 761
ucguauaaca auaaggggcu u 21
<210> 762
<211> 23
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,12,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,10,11,13,15,17,19,21,23
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3,22,23
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 762
ucguauaaca auaaggggcu gcc 23
<210> 763
<211> 24
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 3,5,7,13,15,17,19,21,23
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,9,10,11,12,14,16,18,20,22,24
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 3,4,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 763
tucguauaac aauaaggggc ugcc 24
<210> 764
<211> 24
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 3,5,7,13,15,17,19,21
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,9,10,11,12,14,16,18,20,22,23,24
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 3,4,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 764
tucguauaac aauaaggggc ugcc 24
<210> 765
<211> 24
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 3,5,7,13,15,17,19,21
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,9,10,11,12,14,16,18,20,22,23,24
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 3,4,5,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 765
tucguauaac aauaaggggc ugcc 24
<210> 766
<211> 24
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 3,5,7,13,15,17,19,21
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,9,10,11,12,14,16,18,20,22,23,24
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 3,4,5,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 766
tucguauaac aauaaggggc ugcc 24
<210> 767
<211> 22
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 3,5,7,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,9,10,11,12,14,16,18,20,21,22
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 3,4,5,22
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 767
tucguauaac aauaaggggc ug 22
<210> 768
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,9,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,11,12,13,15,17,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3,4,21
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end ethyl phosphonate modification"
<400> 768
tcguauaaca auaaggggcu u 21
<210> 769
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,9,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,11,12,13,15,17,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 2,3,4,21
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end ethyl phosphonate modification"
<400> 769
tcguauaaca auaaggggcu u 21
<210> 770
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,12,13,15,17,19,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,21,22
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 770
ugagaaugag ccucgauaac ucuuau 26
<210> 771
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,12,13,15,17,19,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,20,21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 771
ugagaaugag ccucgauaac ucuuau 26
<210> 772
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,12,13,15,17,19,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 772
ugagaaugag ccucgauaac uaucgc 26
<210> 773
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,12,13,15,17,19,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 773
ugagaaugag ccucgauaac uauuca 26
<210> 774
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,12,13,15,17,19,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 774
ugagaaugag ccucgauaac uacgau 26
<210> 775
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 4,6,8,10,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,12,13,15,17,19,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 2
<223> /mod_base = "5'-methyl, 2'-fluoro nucleoside"
<400> 775
ugagaaugag ccucgauaac ucuuau 26
<210> 776
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,6,8,10,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,12,13,15,17,19,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 4
<223> /mod_base = "5'-methyl, 2'-fluoro nucleoside"
<400> 776
ugagaaugag ccucgauaac ucuuau 26
<210> 777
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,10,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,12,13,15,17,19,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 8
<223> /mod_base = "5'-methyl, 2'-fluoro nucleoside"
<400> 777
ugagaaugag ccucgauaac ucuuau 26
<210> 778
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,12,13,15,17,19,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 10
<223> /mod_base = "5'-methyl, 2'-fluoro nucleoside"
<400> 778
ugagaaugag ccucgauaac ucuuau 26
<210> 779
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,9,10,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,11,12,13,15,17,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3,4,21
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end Vinyl Phosphonate modification"
<400> 779
ucguauaaca auaaggggcg u 21
<210> 780
<211> 24
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,12,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,10,11,13,15,17,19,21,23,24
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 780
ucguauaaca auaaggggcu gccu 24
<210> 781
<211> 24
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,12,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,10,11,13,15,17,19,21,23,24
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 781
ucguauaaca auaaggggcu gcuu 24
<210> 782
<211> 24
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,12,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,10,11,13,15,17,19,21,23,24
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end Vinyl Phosphonate modification"
<400> 782
ucguauaaca auaaggggcu gccu 24
<210> 783
<211> 24
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,12,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,10,11,13,15,17,19,21,23,24
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end Vinyl Phosphonate modification"
<400> 783
ucguauaaca auaaggggcu gcuu 24
<210> 784
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,9,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,10,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,22,23
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 784
ugagaaugag ccucgauaac ucuuau 26
<210> 785
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,12,13,15,17,19,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end cyclopropyl phosphonate modification"
<400> 785
ugagaaugag ccucgauaac ucuuau 26
<210> 786
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,12,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,10,11,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end cyclopropyl phosphonate modification"
<400> 786
ucguauaaca auaaggggcu gccuau 26
<210> 787
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,10,11,13,15,17,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3,20,21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 787
ucguauaaca auaaggggcu u 21
<210> 788
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,10,11,13,15,17,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3,20,21
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end cyclopropyl phosphonate modification"
<400> 788
ucguauaaca auaaggggcu u 21
<210> 789
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,10,11,13,15,17,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3,20,21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 789
ucguauaaca auaaggggcu g 21
<210> 790
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,12,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,10,11,13,15,17,19,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3,20,21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 790
ucguauaaca auaaggggcu g 21
<210> 791
<211> 24
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,12,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,10,11,13,15,17,19,21,23,24
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end cyclopropyl phosphonate modification"
<400> 791
ucguauaaca auaaggggcu gcuu 24
<210> 792
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 792
ugagaaugag ccucgauaac ucuuau 26
<210> 793
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end cyclopropyl phosphonate modification"
<400> 793
ugagaaugag ccucgauaac ucuuau 26
<210> 794
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end cyclopropyl phosphonate modification"
<400> 794
tgagaaugag ccucgauaac ucuuau 26
<210> 795
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,12,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,8,9,10,11,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end cyclopropyl phosphonate modification"
<400> 795
tcguauaaca auaaggggcu gccuau 26
<210> 796
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,8,9,10,11,13,15,17,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 2,3,20,21
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end cyclopropyl phosphonate modification"
<400> 796
tcguauaaca auaaggggcu u 21
<210> 797
<211> 24
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,12,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,8,9,10,11,13,15,17,19,21,23,24
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end cyclopropyl phosphonate modification"
<400> 797
tcguauaaca auaaggggcu gcuu 24
<210> 798
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3,4,21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 798
ucguauaaca auaaggggcu u 21
<210> 799
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 10,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 799
ugagaaugag ccucgauaac ucuuau 26
<210> 800
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 8,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,9,10,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 800
ugagaaugag ccucgauaac ucuuau 26
<210> 801
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 6,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,7,8,9,10,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 801
ugagaaugag ccucgauaac ucuuau 26
<210> 802
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 4,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,5,6,7,8,9,10,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 802
ugagaaugag ccucgauaac ucuuau 26
<210> 803
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,8,9,10,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 803
ugagaaugag ccucgauaac ucuuau 26
<210> 804
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,3,4,5,6,7,8,9,10,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 804
tgagaaugag ccucgauaac ucuuau 26
<210> 805
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,8,9,10,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 805
tgagaaugag ccucgauaac ucuuau 26
<210> 806
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,10,14,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,8,9,11,12,13,15,16,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 806
tgagaaugag ccucgauaac ucuuau 26
<210> 807
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,14,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,10,11,12,13,15,16,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 807
tgagaaugag ccucgauaac ucuuau 26
<210> 808
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,14,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,8,9,10,11,12,13,15,16,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 808
tgagaaugag ccucgauaac ucuuau 26
<210> 809
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,14,16,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,8,9,10,11,12,13,15,17,18,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 809
tgagaaugag ccucgauaac ucuuau 26
<210> 810
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,10,14,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,8,9,11,12,13,15,16,17,18,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 810
tgagaaugag ccucgauaac ucuuau 26
<210> 811
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,14,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,10,11,12,13,15,16,17,18,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 811
tgagaaugag ccucgauaac ucuuau 26
<210> 812
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 10,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,3,4,5,6,7,8,9,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 812
tgagaaugag ccucgauaac ucuuau 26
<210> 813
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 8,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,3,4,5,6,7,9,10,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 813
tgagaaugag ccucgauaac ucuuau 26
<210> 814
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 6,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,3,4,5,7,8,9,10,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 814
tgagaaugag ccucgauaac ucuuau 26
<210> 815
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 4,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,3,5,6,7,8,9,10,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 815
tgagaaugag ccucgauaac ucuuau 26
<210> 816
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,4,5,6,7,8,9,10,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 816
tgagaaugag ccucgauaac ucuuau 26
<210> 817
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,10,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 817
ugagaaugag ccucgauaac ucuuau 26
<210> 818
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,10,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 818
ugagaaugag ccucgauaac ucuuau 26
<210> 819
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,10,14,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,12,13,15,16,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 819
ugagaaugag ccucgauaac ucuuau 26
<210> 820
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,14,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,10,11,12,13,15,16,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 820
ugagaaugag ccucgauaac ucuuau 26
<210> 821
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,14,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,10,11,12,13,15,16,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 821
ugagaaugag ccucgauaac ucuuau 26
<210> 822
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,14,16,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,10,11,12,13,15,17,18,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 822
ugagaaugag ccucgauaac ucuuau 26
<210> 823
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,14,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,10,11,12,13,15,16,17,18,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 823
ugagaaugag ccucgauaac ucuuau 26
<210> 824
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 4,6,10,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,5,7,8,9,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 824
ugacaccuga uucuguuucu gaguau 26
<210> 825
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 4,6,8,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,5,7,9,10,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 825
ugacaccuga uucuguuucu gaguau 26
<210> 826
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 4,6,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,3,5,7,8,9,10,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 826
tgacaccuga uucuguuucu gaguau 26
<210> 827
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,10,14,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,8,9,11,12,13,15,16,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 827
tgacaccuga uucuguuucu gaguau 26
<210> 828
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,14,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,10,11,12,13,15,16,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 828
tgacaccuga uucuguuucu gaguau 26
<210> 829
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,14,16,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,10,11,12,13,15,17,18,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 829
tgacaccuga uucuguuucu gaguau 26
<210> 830
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,16,17,18,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 830
tgacaccuga uucuguuucu gaguau 26
<210> 831
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,18,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,16,17,19,20,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 831
tgacaccuga uucuguuucu gaguau 26
<210> 832
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,17,18,19,20,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 832
tgacaccuga uucuguuucu gaguau 26
<210> 833
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,16,17,18,19,20,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 833
tgacaccuga uucuguuucu gaguau 26
<210> 834
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,16,17,18,19,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 834
tgacaccuga uucuguuucu gaguau 26
<210> 835
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,12,13,15,16,17,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 835
tgacaccuga uucuguuucu gaguau 26
<210> 836
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 4,6,10,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,3,5,7,8,9,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 836
tgacaccuga uucuguuucu gaguau 26
<210> 837
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 4,6,8,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,3,5,7,9,10,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 837
tgacaccuga uucuguuucu gaguau 26
<210> 838
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 4,6,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,5,7,8,9,10,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 838
ugacaccuga uucuguuucu gaguau 26
<210> 839
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,10,14,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,12,13,15,16,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 839
ugacaccuga uucuguuucu gaguau 26
<210> 840
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,14,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,10,11,12,13,15,16,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 840
ugacaccuga uucuguuucu gaguau 26
<210> 841
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,14,16,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,10,11,12,13,15,17,18,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 841
ugacaccuga uucuguuucu gaguau 26
<210> 842
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,12,13,15,16,17,18,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 842
ugacaccuga uucuguuucu gaguau 26
<210> 843
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,18,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,12,13,15,16,17,19,20,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 843
ugacaccuga uucuguuucu gaguau 26
<210> 844
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,16,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,12,13,15,17,18,19,20,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 844
ugacaccuga uucuguuucu gaguau 26
<210> 845
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,12,13,15,16,17,18,19,20,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 845
ugacaccuga uucuguuucu gaguau 26
<210> 846
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,12,13,15,16,17,18,19,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 846
ugacaccuga uucuguuucu gaguau 26
<210> 847
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,14,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,12,13,15,16,17,19,20,21,22,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 847
ugacaccuga uucuguuucu gaguau 26
<210> 848
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2,8,10,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,4,5,6,7,9,11,12,13,15,17,19,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 848
tgacaccuga uucuguuucu gaguau 26
<210> 849
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 849
acgcagaagg gacugccgat 20
<210> 850
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 850
ggggugcagg agugcuacat 20
<210> 851
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 851
cuguggcagc cccuuauuat 20
<210> 852
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 852
ggcagccccu uauuguuaat 20
<210> 853
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 853
agccccuuau uguuauacat 20
<210> 854
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 854
gccccuuauu guuauacgat 20
<210> 855
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 855
ugacacaaug cucagacgat 20
<210> 856
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 856
gacacaaugc ucagacgcat 20
<210> 857
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 857
acacaaugcu cagacgcaat 20
<210> 858
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 858
acaaugcuca gacgcagaat 20
<210> 859
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 859
cugccgaaau ccagauccat 20
<210> 860
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 860
gccgaaaucc agauccugat 20
<210> 861
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 861
ugacacgaug cucagaugat 20
<210> 862
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 862
gacacgaugc ucagaugcat 20
<210> 863
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 863
acacgaugcu cagaugcaat 20
<210> 864
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 864
acgaugcuca gaugcagaat 20
<210> 865
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 865
uccaagccua gaggcuuuat 20
<210> 866
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 866
aggaaacccc cgggguacat 20
<210> 867
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 867
ggaaaccccc gggguacaat 20
<210> 868
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 868
gaaacccccg ggguacagat 20
<210> 869
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 869
ugcuacuacc auuauggaat 20
<210> 870
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 870
gcuacuacca uuauggacat 20
<210> 871
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 871
cuaccauuau ggacagagat 20
<210> 872
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 872
accacaccag cauagucgat 20
<210> 873
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 873
ccacaccagc auagucggat 20
<210> 874
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 874
cacaccagca uagucggaat 20
<210> 875
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 875
caccagcaua gucggaccat 20
<210> 876
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 876
auagucggac cccagaaaat 20
<210> 877
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 877
uagucggacc ccagaaaaat 20
<210> 878
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 878
ccagaugcug agauucgcat 20
<210> 879
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 879
gcugagauuc gcccuuggat 20
<210> 880
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 880
cugagauucg cccuugguat 20
<210> 881
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 881
ugagauucgc ccuuggugat 20
<210> 882
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 882
gagauucgcc cuugguguat 20
<210> 883
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 883
auggauccca gugucaggat 20
<210> 884
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 884
gaaucaagug uccuugcaat 20
<210> 885
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 885
aaucaagugu ccuugcaaat 20
<210> 886
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 886
gaagcaccaa cggagcaaat 20
<210> 887
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 887
gaguuaucga ggcucauuat 20
<210> 888
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 888
aguuaucgag gcucauucat 20
<210> 889
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 889
gacaacagaa uauuauccat 20
<210> 890
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 890
cuugguguua uaccauggat 20
<210> 891
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 891
gguguuauac cauggaucat 20
<210> 892
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 892
uauaccaugg aucccaauat 20
<210> 893
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 893
auaccaugga ucccaaugat 20
<210> 894
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 894
uaccauggau cccaauguat 20
<210> 895
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 895
accauggauc ccaaugucat 20
<210> 896
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 896
gcaaccugac acaaugucat 20
<210> 897
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 897
cugacacaau guccagugat 20
<210> 898
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 898
ccagugacag aaucaaguat 20
<210> 899
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 899
uuaucgaggc ucauucucat 20
<210> 900
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 900
agaauacuac ccaaauggat 20
<210> 901
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 901
aauacuaccc aaauggugat 20
<210> 902
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 902
auacuaccca aaugguggat 20
<210> 903
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 903
auucgcccuu gguguuauat 20
<210> 904
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 904
uauaccaugg aucccaguat 20
<210> 905
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 905
auaccaugga ucccagugat 20
<210> 906
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 906
cacaacuccc acggugguat 20
<210> 907
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 907
aagaacaugu cagucuugat 20
<210> 908
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 908
aguguccuca caacucccat 20
<210> 909
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 909
aacaagcacc accugagaat 20
<210> 910
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 910
ccugagaaaa gcccugugat 20
<210> 911
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 911
ugauaccaca cuggcaucat 20
<210> 912
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 912
gauaccacac uggcaucaat 20
<210> 913
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 913
gaaacagaau caggugucat 20
<210> 914
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 914
aaacagaauc agguguccat 20
<210> 915
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 915
cagaaucagg uguccuagat 20
<210> 916
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 916
ccuguggcag ccccuuauat 20
<210> 917
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 917
uggcagcccc uuauuguuat 20
<210> 918
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 918
acaccagcau agucggacat 20
<210> 919
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 919
ggaauccaga ugcugagaat 20
<210> 920
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 920
uccagaugcu gagauucgat 20
<210> 921
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 921
augcugagau ucgcccuuat 20
<210> 922
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 922
ccauggaucc cagugucaat 20
<210> 923
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 923
cugaagaagc accaacggat 20
<210> 924
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 924
uccagugaca gaaucaagat 20
<210> 925
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 925
cucacaacuc ccacggugat 20
<210> 926
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 926
agaaucaggu guccuagaat 20
<210> 927
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 927
ucaggugucc uagagacuat 20
<210> 928
<211> 23
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 4,6,8,10,11,12,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,13,15,17,19,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 23
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (Chol-TEG)modification"
<400> 928
uauagccccu uauuguuaua cat 23
<210> 929
<211> 23
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 4,6,8,10,11,12,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,13,15,17,19,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 23
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (Chol-TEG) modification"
<400> 929
uaugccccuu auuguuauac gat 23
<210> 930
<211> 23
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 4,6,8,10,11,12,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,13,15,17,19,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 23
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (Chol-TEG) modification"
<400> 930
uaugacacaa ugcucagacg cat 23
<210> 931
<211> 23
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 4,6,8,10,11,12,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,13,15,17,19,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 23
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (Chol-TEG) modification"
<400> 931
uauacacaau gcucagacgc aat 23
<210> 932
<211> 23
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 4,6,8,10,11,12,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,13,15,17,19,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 23
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (Chol-TEG) modification"
<400> 932
uauuuaucga ggcucauucu cat 23
<210> 933
<211> 23
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 4,6,8,10,11,12,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,13,15,17,19,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 23
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (Chol-TEG) modification"
<400> 933
uaugaaacag aaucaggugu cat 23
<210> 934
<211> 23
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 4,6,8,10,11,12,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,13,15,17,19,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 23
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (Chol-TEG) modification"
<400> 934
uauacaccag cauagucgga cat 23
<210> 935
<211> 23
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 4,6,8,10,11,12,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,13,15,17,19,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 23
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (Chol-TEG) modification"
<400> 935
uauuccagau gcugagauuc gat 23
<210> 936
<211> 23
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 4,6,8,10,12,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 23
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (Chol-TEG) modification"
<400> 936
uauaugcuga gauucgcccu uat 23
<210> 937
<211> 23
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 4,6,8,10,11,12,14,16,18,20,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,13,15,17,19,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 23
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (Chol-TEG) modification"
<400> 937
uauccaugga ucccaguguc aat 23
<210> 938
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 938
uguggcagcc ccuuauugat 20
<210> 939
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 939
cacaaugcuc agacgcagat 20
<210> 940
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 940
ccgaaaucca gauccuguat 20
<210> 941
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 941
gacugaggaa acccccggat 20
<210> 942
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 942
cuacuaccau uauggacaat 20
<210> 943
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 943
acuaccauua uggacagaat 20
<210> 944
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 944
uaccauuaug gacagaguat 20
<210> 945
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 945
accauuaugg acagaguuat 20
<210> 946
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 946
agaugcugag auucgcccat 20
<210> 947
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 947
gaugcugaga uucgcccuat 20
<210> 948
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 948
agauucgccc uugguguuat 20
<210> 949
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 949
gacagaauca aguguccuat 20
<210> 950
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 950
acaugucagu cuugguccat 20
<210> 951
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 951
ccaaauggug gccugaccat 20
<210> 952
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 952
ugguguuaua ccauggauat 20
<210> 953
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 953
uguuauacca uggaucccat 20
<210> 954
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 954
aaccugacac aauguccaat 20
<210> 955
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 955
aauguccagu gacagaauat 20
<210> 956
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 956
uguuucugaa caagcaccat 20
<210> 957
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 957
uaucgaggcu cauucuccat 20
<210> 958
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 958
ucgaggcuca uucuccacat 20
<210> 959
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 959
uccucacaac ucccacggat 20
<210> 960
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 960
caacucccac ggugguccat 20
<210> 961
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 961
gcuccuucug aacaagcaat 20
<210> 962
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 962
auaccacacu ggcaucagat 20
<210> 963
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 963
acagaaucag guguccuaat 20
<210> 964
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 964
gaaucaggug uccuagagat 20
<210> 965
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 965
aaucaggugu ccuagagaat 20
<210> 966
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,10,12,14,16,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "inverted nucleoside"
<400> 966
aucagguguc cuagagacat 20
<210> 967
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,16,18,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C6-SS-Alk-Me) modification"
<400> 967
uauauaguua ucgaggcuca uucuca 26
<210> 968
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,15,16,18,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,14,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C6-SS-Alk-Me) modification"
<400> 968
uauauaguua ucgaggcuca uucuca 26
<210> 969
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,13,15,16,18,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,14,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C6-SS-Alk-Me) modification"
<400> 969
uauauaguua ucgaggcuca uucuca 26
<210> 970
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 7,9,11,13,15,16,18,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,8,10,12,14,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C6-SS-Alk-Me) modification"
<400> 970
uauauaguua ucgaggcuca uucuca 26
<210> 971
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,16,18,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C6-SS-Alk-Me) modification"
<400> 971
uauaucagaa acagaaucag guguca 26
<210> 972
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,15,16,18,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,14,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C6-SS-Alk-Me) modification"
<400> 972
uauaucagaa acagaaucag guguca 26
<210> 973
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,13,15,16,18,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,14,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C6-SS-Alk-Me) modification"
<400> 973
uauaucagaa acagaaucag guguca 26
<210> 974
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 7,9,11,13,15,16,18,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,8,10,12,14,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C6-SS-Alk-Me) modification"
<400> 974
uauaucagaa acagaaucag guguca 26
<210> 975
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,15,16,18,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C11-PEG3-NAG3) modification"
<400> 975
uauaucagcc ccuuauuguu auacga 26
<210> 976
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,15,16,18,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C11-PEG3-NAG3) modification"
<400> 976
uauaucugac acaaugcuca gacgca 26
<210> 977
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,15,16,18,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C11-PEG3-NAG3) modification"
<400> 977
uauauugaca caaugcucag acgcaa 26
<210> 978
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,15,16,18,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C11-PEG3-NAG3) modification"
<400> 978
uauauaguua ucgaggcuca uucuca 26
<210> 979
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,15,16,18,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C11-PEG3-NAG3) modification"
<400> 979
uauaucagaa acagaaucag guguca 26
<210> 980
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,15,16,18,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C11-PEG3-NAG3) modification"
<400> 980
uauauagaug cugagauucg cccuua 26
<210> 981
<211> 18
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 18
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 981
gcagccccuu auuguuaa 18
<210> 982
<211> 18
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 18
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 982
gccccuuauu guuauaca 18
<210> 983
<211> 18
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 18
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 983
ccccuuauug uuauacga 18
<210> 984
<211> 18
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 18
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 984
acacaaugcu cagacgca 18
<210> 985
<211> 18
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 18
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 985
cacaaugcuc agacgcaa 18
<210> 986
<211> 18
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 18
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 986
ccgaaaucca gauccuga 18
<210> 987
<211> 18
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 18
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 987
cacgaugcuc agaugcaa 18
<210> 988
<211> 18
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 18
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 988
ccacaccagc auagucga 18
<210> 989
<211> 18
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 18
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 989
uagucggacc ccagaaaa 18
<210> 990
<211> 18
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 18
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 990
cagaugcuga gauucgca 18
<210> 991
<211> 18
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 18
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 991
aaucaagugu ccuugcaa 18
<210> 992
<211> 18
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 18
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 992
aguuaucgag gcucauua 18
<210> 993
<211> 18
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 18
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 993
guuaucgagg cucauuca 18
<210> 994
<211> 18
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 18
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 994
caaccugaca caauguca 18
<210> 995
<211> 18
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 18
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 995
uaucgaggcu cauucuca 18
<210> 996
<211> 18
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 18
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 996
gaauacuacc caaaugga 18
<210> 997
<211> 18
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 18
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 997
auacuaccca aaugguga 18
<210> 998
<211> 18
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 18
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 998
aaacagaauc agguguca 18
<210> 999
<211> 18
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 18
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 999
aacagaauca ggugucca 18
<210> 1000
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1000
cagccccuua uuguuaa 17
<210> 1001
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1001
ccccuuauug uuauaca 17
<210> 1002
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1002
cccuuauugu uauacga 17
<210> 1003
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1003
cacaaugcuc agacgca 17
<210> 1004
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1004
acaaugcuca gacgcaa 17
<210> 1005
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1005
cgaaauccag auccuga 17
<210> 1006
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1006
acgaugcuca gaugcaa 17
<210> 1007
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1007
cacaccagca uagucga 17
<210> 1008
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1008
agucggaccc cagaaaa 17
<210> 1009
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1009
agaugcugag auucgca 17
<210> 1010
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1010
aucaaguguc cuugcaa 17
<210> 1011
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1011
guuaucgagg cucauua 17
<210> 1012
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1012
uuaucgaggc ucauuca 17
<210> 1013
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1013
aaccugacac aauguca 17
<210> 1014
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1014
aucgaggcuc auucuca 17
<210> 1015
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1015
aauacuaccc aaaugga 17
<210> 1016
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1016
uacuacccaa augguga 17
<210> 1017
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1017
aacagaauca gguguca 17
<210> 1018
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1018
acagaaucag gugucca 17
<210> 1019
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,12,14,15,16,18,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,10,11,13,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C11-PEG3-NAG3) modification"
<400> 1019
uauauaguua ucgaggcuca uucuca 26
<210> 1020
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,7,8,9,10,11,12,13,15,17,18,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C11-PEG3-NAG3) modification"
<400> 1020
uauauaguua ucgaggcuca uucuca 26
<210> 1021
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,7,8,9,10,11,12,13,14,17,18,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C11-PEG3-NAG3) modification"
<400> 1021
uauauaguua ucgaggcuca uucuca 26
<210> 1022
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 12,15,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,7,8,9,10,11,13,14,17,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C11-PEG3-NAG3) modification"
<400> 1022
uauaucagaa acagaaucag guguca 26
<210> 1023
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,7,8,9,10,11,13,15,17,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C11-PEG3-NAG3) modification"
<400> 1023
uauaucagaa acagaaucag guguca 26
<210> 1024
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,7,8,9,10,11,12,13,15,17,18,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C11-PEG3-NAG3) modification"
<400> 1024
uauaucagaa acagaaucag guguca 26
<210> 1025
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,7,8,9,10,11,12,13,14,17,18,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C11-PEG3-NAG3) modification"
<400> 1025
uauaucagaa acagaaucag guguca 26
<210> 1026
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,15,16,18,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (Stearyl) modification"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C11-PEG3-NAG3) modification"
<400> 1026
uauaucagaa acagaaucag guguca 26
<210> 1027
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,10,12,14,15,16,18,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C11-PEG3-NAG3) modification"
<400> 1027
uauaucagaa acagaaucag guguca 26
<210> 1028
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,12,14,15,16,18,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,10,11,13,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C11-PEG3-NAG3) modification"
<400> 1028
uauaucagaa acagaaucag guguca 26
<210> 1029
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,12,16,18,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,10,11,13,14,15,17,19,20,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C11-PEG3-NAG3) modification"
<400> 1029
uauaucagaa acagaaucag guguca 26
<210> 1030
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,15,16,18,21,23,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,17,19,20,22,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C11-PEG3-NAG3) modification"
<400> 1030
uauaucagaa acagaaucag guguca 26
<210> 1031
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,17,18,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C11-PEG3-NAG3) modification"
<400> 1031
uauaucagaa acagaaucag guguca 26
<210> 1032
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,15,16,18,24
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,17,19,20,21,22,23,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C11-PEG3-NAG3) modification"
<400> 1032
uauaucagaa acagaaucag guguca 26
<210> 1033
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,15,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,17,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C11-PEG3-NAG3) modification"
<400> 1033
uauaucagaa acagaaucag guguca 26
<210> 1034
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,12,14,15,16,18,24
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,10,11,13,17,19,20,21,22,23,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C11-PEG3-NAG3) modification"
<400> 1034
uauaucagaa acagaaucag guguca 26
<210> 1035
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,16,18,20,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19,21,22,23,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C11-PEG3-NAG3) modification"
<400> 1035
uauaucagaa acagaaucag guguca 26
<210> 1036
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,15,16,18,20,22,24
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,17,19,21,23
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25,26
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C11-PEG3-NAG3) modification"
<400> 1036
uauauaguua ucgaggcuca uucuca 26
<210> 1037
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 5
<223> /mod_base = "2'-3' seco nucleoside"
<220>
<221> modified_base
<222> 6,8,10,12,14,15,16,18,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,7,9,11,13,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 7,8
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C11-PEG3-NAG3) modification"
<400> 1037
uauauaguua ucgaggcuca uucuca 26
<210> 1038
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,15,16,18,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 7,8
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C11-PEG3-NAG3) modification"
<400> 1038
uauauaguua ucgaggcuca uucuca 26
<210> 1039
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,15,16,18,20,22,24
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,17,19,21,23,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C11-PEG3-NAG3) modification"
<400> 1039
uauaucagcc ccuuauuguu auacga 26
<210> 1040
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 8,10,12,14,15,16,18,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,7,9,11,13,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C11-PEG3-NAG3) modification"
<400> 1040
uauaucagcc ccuuauuguu auacga 26
<210> 1041
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 8,10,12,14,15,16,18,20,22,24
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,7,9,11,13,17,19,21,23,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C11-PEG3-NAG3) modification"
<400> 1041
uauaucagcc ccuuauuguu auacga 26
<210> 1042
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,15,16,18,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C6-PEG4-NAG3) modification"
<400> 1042
uauauaguua ucgaggcuca uucuca 26
<210> 1043
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,15,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,17,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1043
uauauaguua ucgaggcuca uucuca 26
<210> 1044
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,17,18,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1044
uauauaguua ucgaggcuca uucuca 26
<210> 1045
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,12,14,15,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,10,11,13,17,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1045
uauauaguua ucgaggcuca uucuca 26
<210> 1046
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,12,14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,10,11,13,17,18,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1046
uauauaguua ucgaggcuca uucuca 26
<210> 1047
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 12,14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,7,8,9,10,11,13,17,18,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1047
uauauaguua ucgaggcuca uucuca 26
<210> 1048
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,7,8,9,10,11,12,13,17,18,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1048
uauauaguua ucgaggcuca uucuca 26
<210> 1049
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,15,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,17,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1049
uauauaguua ucgaggcuca uucuca 26
<210> 1050
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,15
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,17,18,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1050
uauauaguua ucgaggcuca uucuca 26
<210> 1051
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,12,14,15,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,10,11,13,17,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1051
uauauaguua ucgaggcuca uucuca 26
<210> 1052
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,12,14,15
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,10,11,13,17,18,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1052
uauauaguua ucgaggcuca uucuca 26
<210> 1053
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 12,14,15
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,7,8,9,10,11,13,17,18,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1053
uauauaguua ucgaggcuca uucuca 26
<210> 1054
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 14,15
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,7,8,9,10,11,12,13,17,18,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1054
uauauaguua ucgaggcuca uucuca 26
<210> 1055
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,15,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,14,17,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1055
uauauaguua ucgaggcuca uucuca 26
<210> 1056
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,14,17,18,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1056
uauauaguua ucgaggcuca uucuca 26
<210> 1057
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,12,15,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,10,11,13,14,17,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1057
uauauaguua ucgaggcuca uucuca 26
<210> 1058
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,12,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,10,11,13,14,17,18,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1058
uauauaguua ucgaggcuca uucuca 26
<210> 1059
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 12,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,7,8,9,10,11,13,14,17,18,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1059
uauauaguua ucgaggcuca uucuca 26
<210> 1060
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,7,8,9,10,11,12,13,14,17,18,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1060
uauauaguua ucgaggcuca uucuca 26
<210> 1061
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,15,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,17,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C11-PEG3-NAG3) modification"
<400> 1061
uauauaguua ucgaggcuca uucuca 26
<210> 1062
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,12,14,15,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,10,11,13,17,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C11-PEG3-NAG3) modification"
<400> 1062
uauauaguua ucgaggcuca uucuca 26
<210> 1063
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,15,16,18,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1063
uauauaguua ucgaggcuca uucuca 26
<210> 1064
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,15,16,18,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1064
uauaucagcc ccuuauuguu auacga 26
<210> 1065
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,10,12,14,16,20,22,24
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17,18,19,21,23,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1065
uauaucagcc ccuuauuguu auacga 26
<210> 1066
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,10,12,14,16,24
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17,18,19,20,21,22,23,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1066
uauaucagcc ccuuauuguu auacga 26
<210> 1067
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,7,8,9,10,11,12,13,15,17,18,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1067
uauaucagcc ccuuauuguu auacga 26
<210> 1068
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,7,8,9,10,11,12,13,14,17,18,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1068
uauaucagcc ccuuauuguu auacga 26
<210> 1069
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,10,12,14,15,16,20,22,24
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,17,18,19,21,23,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1069
uauaucagcc ccuuauuguu auacga 26
<210> 1070
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,10,12,14,15,16,24
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,17,18,19,20,21,22,23,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1070
uauaucagcc ccuuauuguu auacga 26
<210> 1071
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,7,8,9,10,11,12,13,17,18,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1071
uauaucagcc ccuuauuguu auacga 26
<210> 1072
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,10,12,15,16,24
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,14,17,18,19,20,21,22,23,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1072
uauaucagcc ccuuauuguu auacga 26
<210> 1073
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,7,8,9,10,11,12,13,15,17,18,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C11-PEG3-NAG3) modification"
<400> 1073
uauaucagcc ccuuauuguu auacga 26
<210> 1074
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,10,12,14,16,20,22,24
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17,18,19,21,23,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C11-PEG3-NAG3) modification"
<400> 1074
uauaucagcc ccuuauuguu auacga 26
<210> 1075
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,10,12,14,16,24
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17,18,19,20,21,22,23,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C11-PEG3-NAG3) modification"
<400> 1075
uauaucagcc ccuuauuguu auacga 26
<210> 1076
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,7,8,9,10,11,12,13,14,17,18,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C11-PEG3-NAG3) modification"
<400> 1076
uauaucagcc ccuuauuguu auacga 26
<210> 1077
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,10,12,14,15,16,20,22,24
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,17,18,19,21,23,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C11-PEG3-NAG3) modification"
<400> 1077
uauaucagcc ccuuauuguu auacga 26
<210> 1078
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,10,12,14,15,16,24
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,17,18,19,20,21,22,23,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C11-PEG3-NAG3) modification"
<400> 1078
uauaucagcc ccuuauuguu auacga 26
<210> 1079
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,7,8,9,10,11,12,13,17,18,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C11-PEG3-NAG3) modification"
<400> 1079
uauaucagcc ccuuauuguu auacga 26
<210> 1080
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,10,12,15,16,24
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,14,17,18,19,20,21,22,23,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C11-PEG3-NAG3) modification"
<400> 1080
uauaucagcc ccuuauuguu auacga 26
<210> 1081
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,7,8,9,10,11,12,13,17,18,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C11-PEG3-NAG3) modification"
<400> 1081
uauauaguua ucgaggcuca uucuca 26
<210> 1082
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,7,8,9,10,11,12,13,14,17,18,19,20,21,22,23,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (Chol-TEG) modification"
<400> 1082
uauauaguua ucgaggcuca uucuca 26
<210> 1083
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,7,8,9,10,11,12,13,14,17,18,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (Chol-TEG) modification"
<400> 1083
uauauaguua ucgaggcuca uucuca 26
<210> 1084
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,15,16,18,20,22,24
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (Chol-TEG) modification"
<400> 1084
uauauaguua ucgaggcuca uucuca 26
<210> 1085
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "3' end (NAG13) modification"
<400> 1085
ccccuuauug uuauaca 17
<210> 1086
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "3' end (NAG13) modification"
<400> 1086
cccuuauugu uauacga 17
<210> 1087
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "3' end (NAG13) modification"
<400> 1087
agaugcugag auucgca 17
<210> 1088
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "3' end (NAG13) modification"
<400> 1088
guuaucgagg cucauua 17
<210> 1089
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "3' end (NAG13) modification"
<400> 1089
aucgaggcuc auucuca 17
<210> 1090
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,8,10,12,14,16,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "3' end (NAG13) modification"
<400> 1090
aacagaauca gguguca 17
<210> 1091
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,7,8,9,10,11,12,13,14,17,18,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (NAG13) modification"
<400> 1091
uauauaguua ucgaggcuca uucuca 26
<210> 1092
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,15,16,18,20,22,24
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,17,19,21,23,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (NAG13) modification"
<400> 1092
uauaucagcc ccuuauuguu auacga 26
<210> 1093
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 12,14,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,7,8,9,10,11,13,15,17,18,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (NAG13) modification"
<400> 1093
uauaucagcc ccuuauuguu auacga 26
<210> 1094
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 15,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,7,8,9,10,11,12,13,14,17,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (NAG13) modification"
<400> 1094
uauaucagcc ccuuauuguu auacga 26
<210> 1095
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,7,8,9,10,11,12,13,17,18,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (NAG13) modification"
<400> 1095
uauaucagcc ccuuauuguu auacga 26
<210> 1096
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,15,16,18,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (C-SS-Alk-Me) modification"
<400> 1096
uauauaguua ucgaggcuca uucuca 26
<210> 1097
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,7,8,9,10,11,12,13,17,18,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (NAG13) modification"
<400> 1097
uauauaguua ucgaggcuca uucuca 26
<210> 1098
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 8,10,12,14,15,16,18,20,22,24
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,7,9,11,13,17,19,21,23,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (NAG13) modification"
<400> 1098
uauaucagcc ccuuauuguu auacga 26
<210> 1099
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,7,8,9,10,11,12,13,17,18,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (NAG13) modification"
<400> 1099
uauaucagcg ccuuauuguu auacga 26
<210> 1100
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 8,10,12,14,15,16,18,20,22,24
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,7,9,11,13,17,19,21,23,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1100
uauaucagcc ccuuauuguu auacga 26
<210> 1101
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 5,6,7
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,8,9,10,11,12,13,14,15,16,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "3' end (NAG13) modification"
<400> 1101
ccccuuauug uuauaca 17
<210> 1102
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 5,6,7
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,8,9,10,11,12,13,14,15
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 16,17
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "3' end (NAG13) modification"
<400> 1102
ccccuuauug uuauaca 17
<210> 1103
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 5,6,7
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,4,8,9,10,11,12,13,14,15
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 1,2,16,17
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "3' end (NAG13) modification"
<400> 1103
ccccuuauug uuauaca 17
<210> 1104
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 5,6,7
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,8,9,10,11,12,13,14,15,16,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "3' end (NAG13) modification"
<400> 1104
cccuuauugu uauacga 17
<210> 1105
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 5,6,7
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,8,9,10,11,12,13,14,15
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 16,17
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "3' end (NAG13) modification"
<400> 1105
cccuuauugu uauacga 17
<210> 1106
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 5,6,7
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,4,8,9,10,11,12,13,14,15
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 1,2,16,17
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "3' end (NAG13) modification"
<400> 1106
cccuuauugu uauacga 17
<210> 1107
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 5,6,7
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,8,9,10,11,12,13,14,15,16,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "3' end (NAG13) modification"
<400> 1107
aucgaggcuc auucuca 17
<210> 1108
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 5,6,7
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,8,9,10,11,12,13,14,15
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 16,17
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "3' end (NAG13) modification"
<400> 1108
aucgaggcuc auucuca 17
<210> 1109
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 5,6,7
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,4,8,9,10,11,12,13,14,15
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 1,2,16,17
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "3' end (NAG13) modification"
<400> 1109
atcgaggcuc auucuca 17
<210> 1110
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 5,6,7
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,8,9,10,11,12,13,14,15,16,17
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "3' end (NAG13) modification"
<400> 1110
aacagaauca gguguca 17
<210> 1111
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 5,6,7
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,8,9,10,11,12,13,14,15
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 16,17
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "3' end (NAG13) modification"
<400> 1111
aacagaauca gguguca 17
<210> 1112
<211> 17
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 5,6,7
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,4,8,9,10,11,12,13,14,15
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 1,2,16,17
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 2,3
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 17
<223> /mod_base = "3' end (NAG13) modification"
<400> 1112
aacagaauca gguguca 17
<210> 1113
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,10,11,12,13,17,18,19,20,21,22,23,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG18) modification"
<400> 1113
uauauaguua ucgaggcuca uucuca 26
<210> 1114
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 8,10,12,14,15,16,18,20,22,24
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,9,11,13,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG18) modification"
<400> 1114
uauaucagcc ccuuauuguu auacga 26
<210> 1115
<211> 24
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 4,6,8,10,11,12,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,5,7,9,13,15,17,19,21,22,23,24
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG4) modification"
<400> 1115
ucagccccuu auuguuauac gauu 24
<210> 1116
<211> 22
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 4,6,8,10,11,12,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,5,7,9,13,15,17,19,21,22
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,22
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG4) modification"
<400> 1116
ucagccccuu auuguuauac ga 22
<210> 1117
<211> 24
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 4,6,8,10,11,12,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,5,7,9,13,15,17,19,21,22,23,24
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG24) modification"
<400> 1117
ucagccccuu auuguuauac gauu 24
<210> 1118
<211> 24
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 10,11,12
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,13,14,15,16,17,18,19,20,21,22,23,24
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG4) modification"
<400> 1118
uaguuaucga ggcucauucu cauu 24
<210> 1119
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 12,14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,7,8,9,10,11,13,17,18,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (NAG13) modification"
<400> 1119
uauaucagcc ccuuauuguu auacga 26
<210> 1120
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 12,14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,7,8,9,10,11,13,17,18,19,20,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "3' end (NAG13) modification"
<400> 1120
uauauaguua ucgaggcuca uucuca 26
<210> 1121
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 8,10,12,14,15,16,18,20,22,24
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,9,11,13,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 6,26
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG4) modification"
<400> 1121
uauaucagcc ccuuauuguu auacga 26
<210> 1122
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,10,12,14,16,18,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG4) modification"
<400> 1122
gccccuuauu guuauacgau u 21
<210> 1123
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,10,11,12,13,17,18,19,20,21,22,23,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG25) modification"
<400> 1123
uauauaguua ucgaggcuca uucuca 26
<210> 1124
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,10,11,12,13,17,18,19,20,21,22,23,24
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (Alk-PEG5-C6) modification"
<400> 1124
uauauaguua ucgaggcuca uucuca 26
<210> 1125
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,10,11,12,13,17,18,19,20,21,22,23,24
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (Alk-SMPT-C6) modification"
<400> 1125
uauauaguua ucgaggcuca uucuca 26
<210> 1126
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,10,11,12,13,17,18,19,20,21,22,23,24
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG26) modification"
<400> 1126
uauauaguua ucgaggcuca uucuca 26
<210> 1127
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,10,11,12,13,17,18,19,20,21,22,23,24
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG27) modification"
<400> 1127
uauauaguua ucgaggcuca uucuca 26
<210> 1128
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 13,14,15
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,10,11,12,16,17,18,19,20,21,22,23,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 5,6
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG25) modification"
<400> 1128
auaucagccc cuuauuguua uacgat 26
<210> 1129
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 12,13,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,10,11,15,16,17,18,19,20,21,22,23,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 4,5
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG25) modification"
<400> 1129
uaucagcccc uuauuguuau acgaut 26
<210> 1130
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 13,14,15
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,10,11,12,16,17,18,19,20,21,22,23,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 5,6
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG25) modification"
<400> 1130
auauaguuau cgaggcucau ucucat 26
<210> 1131
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 12,13,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,10,11,15,16,17,18,19,20,21,22,23,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 4,5
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG25) modification"
<400> 1131
uauaguuauc gaggcucauu cucaut 26
<210> 1132
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,10,11,12,13,17,18,19,20,21,22,23,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG25) modification"
<400> 1132
uauaucagcc ccuuauuguu auacga 26
<210> 1133
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 7,8,9
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,10,11,12,13,14,15,16,17,18,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<400> 1133
gccccuuauu guuauacgau u 21
<210> 1134
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 7,8,9
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,10,11,12,13,14,15,16,17,18,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1134
uuaucgaggc ucauucucau u 21
<210> 1135
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,10,12,14,16,18,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 22
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1135
gccccuuauu guuauacgau u 21
<210> 1136
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,10,11,12,13,17,18,19,20,21,22,23,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG29) modification"
<400> 1136
uauauaguua ucgaggcuca uucuca 26
<210> 1137
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,9,12,14,16,18,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1137
gccccuuauu guuauacgau u 21
<210> 1138
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,10,11,12,13,14,17,18,19,20,21,22,23,24,
25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 8,26
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG29) modification"
<400> 1138
uauauaauua ucgaggcuca uucuca 26
<210> 1139
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,10,12,14,16,18,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1139
gccccuuauu guuauacgau u 21
<210> 1140
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,10,11,12,13,14,17,18,19,20,21,22,23,24,
25,26
<223> /mod_base = "2'-o-methyl nucleoside"
<220>
<221> modified_base
<222> 8,26
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG25) modification"
<400> 1140
uauauaauua ucgaggcuca uucuca 26
<210> 1141
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,10,11,12,13,17,18,19,20,21,22,23,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 7,8
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG25) modification"
<400> 1141
uauaucagcc ccuuauuguu auacga 26
<210> 1142
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,10,11,12,13,17,18,19,20,21,22,23,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 8
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG25) modification"
<400> 1142
uauaucagcc ccuuauuguu auacga 26
<210> 1143
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,10,11,12,13,17,18,19,20,21,22,23,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 7,8
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG25) modification"
<400> 1143
uauauaguua ucgaggcuca uucuca 26
<210> 1144
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,10,11,12,13,17,18,19,20,21,22,23,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 8
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG25) modification"
<400> 1144
uauauaguua ucgaggcuca uucuca 26
<210> 1145
<211> 22
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 4,6,8,10,11,12,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,5,7,9,13,15,17,19,21,22
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,22
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG30) modification"
<400> 1145
ucagccccuu auuguuauac ga 22
<210> 1146
<211> 25
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 11,12,13
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,10,14,15,16,17,18,19,20,21,22
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 24
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 23
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 4,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG25) modification"
<400> 1146
ggcagccccu uauuguuaua cgatt 25
<210> 1147
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 11,12,13
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,10,14,15,16,17,18,19,20,21,22,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 23
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 4,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG25) modification"
<400> 1147
ggcagccccu uauuguuaua cgauut 26
<210> 1148
<211> 25
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1
<223> /mod_base = "2'-3' seco nucleoside"
<220>
<221> modified_base
<222> 11,12,13
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,3,4,5,6,7,8,9,10,14,15,16,17,18,19,20,21,22
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 24
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 23
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 4,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG25) modification"
<400> 1148
ggcagccccu uauuguuaua cgatt 25
<210> 1149
<211> 25
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 11,12,13
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,5,6,7,8,9,10,14,15,16,17,18,19,20,21,22
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 24
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 23
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 4,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG25) modification"
<400> 1149
ggcagccccu uauuguuaua cgatt 25
<210> 1150
<211> 25
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 9,10,11
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,12,13,14,15,16,17,18,19,20
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 22
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 2,22
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG25) modification"
<400> 1150
cagccccuua uuguuauacg atttt 25
<210> 1151
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,10,12,14,16,18,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1151
gccccuuauu guuauacgau u 21
<210> 1152
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,10,12,14,16,18,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1152
gccccuuauu guuauacgau u 21
<210> 1153
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,10,11,12,13,17,18,19,20,21,22,23,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 8,9
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG25) modification"
<400> 1153
uauauaguua ucgaggcuca uucuca 26
<210> 1154
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,10,11,12,13,17,18,19,20,21,22,23,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 9,10
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG25) modification"
<400> 1154
uauauaguua ucgaggcuca uucuca 26
<210> 1155
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,10,11,12,13,17,18,19,20,21,22,23,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG25) modification"
<400> 1155
gcgauaguua ucgaggcuca uucuca 26
<210> 1156
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,10,11,12,13,17,18,19,20,21,22,23,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG25) modification"
<400> 1156
ugaauaguua ucgaggcuca uucuca 26
<210> 1157
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,10,11,12,13,17,18,19,20,21,22,23,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG25) modification"
<400> 1157
aucguaguua ucgaggcuca uucuca 26
<210> 1158
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,8,9,10,11,12,13,17,18,19,20,21,22,23,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,26
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG25) modification"
<400> 1158
uauauaguua ucgaggcuca uucuca 26
<210> 1159
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,6,7,8,9,10,11,12,13,17,18,19,20,21,22,23,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 5,26
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG25) modification"
<400> 1159
uauaaaguua ucgaggcuca uucuca 26
<210> 1160
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,7,8,9,10,11,12,13,17,18,19,20,21,22,23,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG25) modification"
<400> 1160
uauauaguua ucgaggcuca uucuca 26
<210> 1161
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 2,4,6,8,9,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,11,13,15,17,19,20
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 20
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG30) modification"
<400> 1161
agccccuuau uguuauacga 20
<210> 1162
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 3,5,7,9,10,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,4,6,8,12,14,16,18,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG30) modification"
<400> 1162
aagccccuua uuguuauacg a 21
<210> 1163
<211> 20
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 2,4,6,8,9,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,11,13,15,17,19,20
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 1,2
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG30) modification"
<400> 1163
agccccuuau uguuauacga 20
<210> 1164
<211> 22
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 4,6,8,10,11,12,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,5,7,9,13,15,17,19,21,22
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,22
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG30) modification"
<400> 1164
gcagccccuu auuguuauac ga 22
<210> 1165
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,10,11,12,13,14,17,18,19,20,21,22,23,24,
25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 8,26
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG25) modification"
<400> 1165
uauauaguua ucgaggcuca uucuca 26
<210> 1166
<211> 22
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 4,6,8,10,11,12,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,5,7,9,13,15,17,19,21,22
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 1,2,22
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG30) modification"
<400> 1166
gcagccccuu auuguuauac ga 22
<210> 1167
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,10,12,14,16,18,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1167
gccccuuauu guuauacgau u 21
<210> 1168
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,10,12,14,16,18,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1168
gccccuuauu guuauacgau u 21
<210> 1169
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,10,12,14,16,18,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1169
gccccuuauu guuauacgau u 21
<210> 1170
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 3,5,7,9,10,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,4,6,8,12,14,16,18,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG30) modification"
<400> 1170
acgccccuua uuguuauacg a 21
<210> 1171
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 3,5,7,9,10,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,4,6,8,12,14,16,18,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 1,2
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG30) modification"
<400> 1171
aagccccuua uuguuauacg a 21
<210> 1172
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 3,5,7,9,10,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,4,6,8,12,14,16,18,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 1,2
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG30) modification"
<400> 1172
acgccccuua uuguuauacg a 21
<210> 1173
<211> 22
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 4,6,8,10,11,12,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,5,7,9,13,15,17,19,21,22
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 1,2
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG30) modification"
<400> 1173
gcagccccuu auuguuauac ga 22
<210> 1174
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,10,12,14,16,18,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 1,21
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG31)s modification"
<400> 1174
gccccuuauu guuauacgau u 21
<210> 1175
<211> 22
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 2,4,6,8,9,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,11,13,15,17,19,20,21,22
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 1,22
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG31)s modification"
<400> 1175
agccccuuau uguuauacga uu 22
<210> 1176
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 3,5,7,9,10,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,4,6,8,12,14,16,18,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 1,2
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG31)s modification"
<400> 1176
aagccccuua uuguuauacg a 21
<210> 1177
<211> 23
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 3,5,7,9,10,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,4,6,8,12,14,16,18,20,21,22,23
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 1,2,23
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG31)s modification"
<400> 1177
aagccccuua uuguuauacg auu 23
<210> 1178
<211> 23
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 3,5,7,9,10,11,13,15,17,19
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,4,6,8,12,14,16,18,20,22,23
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 1,2,23
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG31)s modification"
<400> 1178
aagccccuua uuguuauacg auu 23
<210> 1179
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,10,11,12,13,17,18,19,20,21,22,23,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG31) modification"
<400> 1179
uauauaguua ucgaggcuca uucuca 26
<210> 1180
<211> 24
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 12,13,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,10,11,15,16,17,18,19,20,21,22,23
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 4,5,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG31) modification"
<400> 1180
uaucagcccc uuauuguuau acga 24
<210> 1181
<211> 24
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 12,13,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,10,11,15,16,17,18,19,20,21,22,23
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 4,5,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG31) modification"
<400> 1181
uagcagcccc uuauuguuau acga 24
<210> 1182
<211> 24
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 12,13,14
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,10,11,15,16,17,18,19,20,21,22,23
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 24
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG31) modification"
<400> 1182
uaucagcccc uuauuguuau acga 24
<210> 1183
<211> 22
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 10,11,12
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,13,14,15,16,17,18,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 1,2,22
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG31)s modification"
<400> 1183
gcagccccuu auuguuauac ga 22
<210> 1184
<211> 22
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 10,11,12
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,13,14,15,16,17,18,19,20,21,22
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 1,2,22
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG31)s modification"
<400> 1184
gcagccccuu auuguuauac ga 22
<210> 1185
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,10,11,12,13,17,18,19,20,21,22,23,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG25) modification"
<400> 1185
auaagaguua ucgaggcuca uucuca 26
<210> 1186
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,10,11,12,13,17,18,19,20,21,22,23,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG25) modification"
<400> 1186
auaagaguua ucgaggcuca uucuca 26
<210> 1187
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,10,11,12,13,17,18,19,20,21,22,23,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG25) modification"
<400> 1187
auaggcagcc ccuuauuguu auacga 26
<210> 1188
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,10,11,12,13,17,18,19,20,21,22,23,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG25) modification"
<400> 1188
auaggcagcc ccuuauuguu auacga 26
<210> 1189
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 9,10,11
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,12,13,14,15,16,17,18,19,20
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 1,2,21
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG25)s modification"
<400> 1189
cagccccuua uuguuauacg a 21
<210> 1190
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 9,10,11
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,12,13,14,15,16,17,18,19,20
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 1,2,21
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG31)s modification"
<400> 1190
cagccccuua uuguuauacg a 21
<210> 1191
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 7,8,9
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,10,11,12,13,14,15,16,17,18,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 1,2
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG25) modification"
<400> 1191
gccccuuauu guuauacgau u 21
<210> 1192
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 7,8,9
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,10,11,12,13,14,15,16,17,18,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 1,2
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG31)s modification"
<400> 1192
gccccuuauu guuauacgau u 21
<210> 1193
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,7,8,9
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,3,4,5,6,10,11,12,13,14,15,16,17,18,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 1,2
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG25)s modification"
<400> 1193
gccccuuauu guuauacgau u 21
<210> 1194
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,10,12,14,16,18,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 1,2
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG31)s modification"
<400> 1194
gccccuuauu guuauacgau u 21
<210> 1195
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,9,10,11,12,17,18,19,20,21,22,23,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 26
<223> /mod_base = "inverted nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 13
<223> /mod_base = "NOTA nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG25) modification"
<400> 1195
uauaucagcc cctuauuguu auacga 26
<210> 1196
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,15,17
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,10,12,14,16,18,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 6
<223> /mod_base = "NOTA nucleoside"
<400> 1196
gcccctuauu guuauacgau u 21
<210> 1197
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,15,16,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,17,18,19,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1197
uauauaguua ucgaggcuca uucuca 26
<210> 1198
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,15,16,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,17,18,19,20,21,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1198
uauauaguua ucgaggcuca uucuca 26
<210> 1199
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,15,16,24
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,17,18,19,20,21,22,23,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1199
uauauaguua ucgaggcuca uucuca 26
<210> 1200
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,15,16,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,17,18,19,20,21,22,23,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1200
uauauaguua ucgaggcuca uucuca 26
<210> 1201
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,16,18,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19,20,21,22,23,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1201
uauauaguua ucgaggcuca uucuca 26
<210> 1202
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,16,20,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,18,19,21,22,23,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1202
uauauaguua ucgaggcuca uucuca 26
<210> 1203
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,16,22,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,18,19,20,21,23,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1203
uauauaguua ucgaggcuca uucuca 26
<210> 1204
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,16,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,18,19,20,21,22,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1204
uauauaguua ucgaggcuca uucuca 26
<210> 1205
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,16,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,18,19,20,21,22,23,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1205
uauauaguua ucgaggcuca uucuca 26
<210> 1206
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,15,16,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,14,17,18,19,20,21,22,23,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1206
uauauaguua ucgaggcuca uucuca 26
<210> 1207
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,16,18,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,14,15,17,19,20,21,22,23,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1207
uauauaguua ucgaggcuca uucuca 26
<210> 1208
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,16,20,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,14,15,17,18,19,21,22,23,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1208
uauauaguua ucgaggcuca uucuca 26
<210> 1209
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,16,22,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,14,15,17,18,19,20,21,23,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1209
uauauaguua ucgaggcuca uucuca 26
<210> 1210
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,16,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,14,15,17,18,19,20,21,22,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1210
uauauaguua ucgaggcuca uucuca 26
<210> 1211
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,16,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,14,15,17,18,19,20,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1211
uauauaguua ucgaggcuca uucuca 26
<210> 1212
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,12,14,16,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,10,11,13,15,17,18,19,20,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1212
uauauaguua ucgaggcuca uucuca 26
<210> 1213
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,12,15,16,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,10,11,13,14,17,18,19,20,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1213
uauauaguua ucgaggcuca uucuca 26
<210> 1214
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,12,16,18,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,10,11,13,14,15,17,19,20,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1214
uauauaguua ucgaggcuca uucuca 26
<210> 1215
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,12,16,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,10,11,13,14,15,17,18,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1215
uauauaguua ucgaggcuca uucuca 26
<210> 1216
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,12,16,18,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,10,11,13,14,15,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1216
uauauaguua ucgaggcuca uucuca 26
<210> 1217
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,10,12,16,18,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,14,15,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1217
uauauaguua ucgaggcuca uucuca 26
<210> 1218
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,12,14,16,18,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,10,11,13,15,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1218
uauauaguua ucgaggcuca uucuca 26
<210> 1219
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,12,15,16,18,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,10,11,13,14,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1219
uauauaguua ucgaggcuca uucuca 26
<210> 1220
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 8,10,14,15,16,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,6,7,9,11,12,13,17,18,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1220
uauaucagaa acagaaucag guguca 26
<210> 1221
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,15,16,18,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1221
uauaucagaa acagaaucag guguca 26
<210> 1222
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,15,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,17,19,21,22,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1222
uauaucagaa acagaaucag guguca 26
<210> 1223
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,15,16,18,24
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,17,19,20,21,22,23,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1223
uauaucagaa acagaaucag guguca 26
<210> 1224
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,15,16,18,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,17,19,20,21,22,23,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1224
uauaucagaa acagaaucag guguca 26
<210> 1225
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,15,16,18,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,17,19,20,21,23,24,25,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1225
uauaucagaa acagaaucag guguca 26
<210> 1226
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,16,18,20,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19,21,22,23,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1226
uauaucagaa acagaaucag guguca 26
<210> 1227
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,16,18,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19,20,21,22,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1227
uauaucagaa acagaaucag guguca 26
<210> 1228
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,14,16,18,22,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19,20,21,23,24,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1228
uauaucagaa acagaaucag guguca 26
<210> 1229
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,15,16,18,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,14,17,19,20,21,22,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1229
uauaucagaa acagaaucag guguca 26
<210> 1230
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,16,18,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,14,15,17,19,20,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1230
uauaucagaa acagaaucag guguca 26
<210> 1231
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,16,18,20,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,14,15,17,19,21,22,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1231
uauaucagaa acagaaucag guguca 26
<210> 1232
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,12,15,16,18,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,10,11,13,14,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1232
uauaucagaa acagaaucag guguca 26
<210> 1233
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,12,14,16,18,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,10,11,13,15,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1233
uauaucagaa acagaaucag guguca 26
<210> 1234
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,10,12,16,18,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,14,15,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1234
uauaucagaa acagaaucag guguca 26
<210> 1235
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,8,12,16,18,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,10,11,13,14,15,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1235
uauaucagaa acagaaucag guguca 26
<210> 1236
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,10,12,16,18,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,14,15,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1236
uauaucagaa acagaaucag guguca 26
<210> 1237
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,12,15,16,18,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,10,11,13,14,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1237
uauaucagaa acagaaucag guguca 26
<210> 1238
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,12,14,16,18,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,10,11,13,15,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1238
uauaucagaa acagaaucag guguca 26
<210> 1239
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,12,14,15,16,18,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,10,11,13,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1239
uauaucagaa acagaaucag guguca 26
<210> 1240
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 6,10,12,15,16,18,20,22,24,26
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,11,13,14,17,19,21,23,25
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,4
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1240
uauaucagaa acagaaucag guguca 26
<210> 1241
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<222> 1,2,3,4,5,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 1241
gcccctuauu guuauacgau u 21
<210> 1242
<211> 19
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 1242
tcguauaaca auaaggggc 19
<210> 1243
<211> 19
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 1243
gccccuuauu guuauacga 19
<210> 1244
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 1244
ucguauaaca auaagggg 18
<210> 1245
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 1245
ccccuuauug uuauacga 18
<210> 1246
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 1246
ucguauaaca auaaggg 17
<210> 1247
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 1247
cccuuauugu uauacga 17
<210> 1248
<211> 19
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<222> 2-19
<223> /mod_base = "2'-hydroxy nucleoside"
<400> 1248
tgagaaugag ccucgauaa 19
<210> 1249
<211> 19
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 1249
uuaucgaggc ucauucuca 19
<210> 1250
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 1250
ugagaaugag ccucgaua 18
<210> 1251
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 1251
uaucgaggcu cauucuca 18
<210> 1252
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 1252
ugagaaugag ccucgau 17
<210> 1253
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 1253
aucgaggcuc auucuca 17
<210> 1254
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 1254
uguauaacaa uaagggg 17
<210> 1255
<211> 17
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 1255
ccccuuauug uuauaca 17
<210> 1256
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<223> 1,3,5,7,8,9,11,13,15,17
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,9,10,12,14,16,18,19,21,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1256
gccccuuauu guuauacgau u 21
<210> 1257
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<223> 9,10,11
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,12,13,14,15,16,17,18,19,20
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 1,2,21
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG37) modification"
<400> 1257
cagccccuua uuguuauacg a 21
<210> 1258
<211> 19
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 1258
uuaucgaggc ucauucuca 19
<210> 1259
<211> 19
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 1259
gccccuuauu guuauacga 19
<210> 1260
<211> 22
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 1260
acagccccuu auuguuauac ga 22
<210> 1261
<211> 22
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<400> 1261
aaagccccuu auuguuauac ga 22
<210> 1262
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<223> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,9,11,13,15,17,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3,4,21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1262
ugagaaugag ccucgauaau u 21
<210> 1263
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<223> 2,4,6,8,9,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,11,13,15,17,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 2,3,4,21
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end cyclopropyl phosphonate modification"
<400> 1263
tcguauaaca auaaggggcu u 21
<210> 1264
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<223> 2,4,6,8,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 3,5,7,9,11,13,15,17,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "2'-MOE nucleoside"
<220>
<221> modified_base
<222> 2,3,4,21
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end cyclopropyl phosphonate modification"
<400> 1264
tcguauaaca auaaggggcu u 21
<210> 1265
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<223> 2,9,12,14,18,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,6,7,8,10,11,13,15,16,17,19,20,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1265
ucguauaaca auaaggggcu gccuau 26
<210> 1266
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<223> 2,6,9,12,14,18,22
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,4,5,7,8,10,11,13,15,16,17,19,20,21,23,24,26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 25
<223> /mod_base = "2'-hydroxy nucleoside"
<220>
<221> modified_base
<222> 2,3,23,24
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1266
ucguauaaca auaaggggcu gccuau 26
<210> 1267
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<223> 2,4,6,12,14,16,18,20
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,8,9,10,11,13,15,17,19,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3,20,21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1267
ucguauaaca auaaggggcu u 21
<210> 1268
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<220>
<221> modified_base
<223> 2,4,6,8,9,10,12,14,16,18
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,3,5,7,11,13,15,17,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 2,3,4,21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1268
ucguauaaca auaaggggcu u 21
<210> 1269
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<223> 14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1-13,17-26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG25) modification"
<400> 1269
uauauaguua ucgaggcuca uucuca 26
<210> 1270
<211> 19
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<223> 7,8,9
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,10,11,12,13,14,15,16,17,18,19
<223> /mod_base = "2'-O-methyl nucleoside"
<400> 1270
uuaucgaggc ucauucuca 19
<210> 1271
<211> 19
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<223> 1,2,5,7,8,9,11,13,15,17
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 2,4,6,10,12,14,16,18,19
<223> /mod_base = "2'-O-methyl nucleoside"
<400> 1271
gccccuuauu guuauacga 19
<210> 1272
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<223> 7,8,9
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,10,11,12,13,14,15,16,17,18,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 21
<223> /mod_base = "phosphorothioate linked nucleoside"
<400> 1272
gccccuuauu guuauacgau u 21
<210> 1273
<211> 26
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<223> 14,15,16
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1-13,17-26
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 6,7
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG25) modification"
<400> 1273
uauaucagcc ccuuauuguu auacga 26
<210> 1274
<211> 19
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<223> 7,8,9
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,10,11,12,13,14,15,16,17,18,19
<223> /mod_base = "2'-O-methyl nucleoside"
<400> 1274
gccccuuauu guuauacga 19
<210> 1275
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<223> 9,10,11
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,12,13,14,15,16,17,18,19,20
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 1,2,21
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG25)s modification"
<400> 1275
aagccccuua uuguuauacg a 21
<210> 1276
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<223> 9,10,11
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,12,13,14,15,16,17,18,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 1,2
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG25)s modification"
<400> 1276
cagccccuua uuguuauacg a 21
<210> 1277
<211> 19
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<223> 7,8,9
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,10,11,12,13,14,15,16,17,18,19
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 1,2
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG25)s modification"
<400> 1277
gccccuuauu guuauacga 19
<210> 1278
<211> 19
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<223> 7,8,9
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,10,11,12,13,14,15,16,17,18
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 1,2,19
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG25)s modification"
<400> 1278
gccccuuauu guuauacga 19
<210> 1279
<211> 21
<212> DNA
<213> artificial sequence
<220>
<223> LPA RNAi agent sense strand
<220>
<221> modified_base
<223> 9,10,11
<223> /mod_base = "2'-deoxy-2'-fluoro nucleoside"
<220>
<221> modified_base
<222> 1,2,3,4,5,6,7,8,12,13,14,15,16,17,18,19,20,21
<223> /mod_base = "2'-O-methyl nucleoside"
<220>
<221> modified_base
<222> 1,2
<223> /mod_base = "phosphorothioate linked nucleoside"
<220>
<221> modified_base
<222> 1
<223> /mod_base = "5' end (NAG25)s modification"
<400> 1279
aagccccuua uuguuauacg a 21
<210> 1280
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 1280
cguauaacaa uaaggggc 18
<210> 1281
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 1281
gagaaugagc cucgauaa 18
<210> 1282
<211> 19
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 1282
ucguauaaca auaaggggc 19
<210> 1283
<211> 19
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent antisense strand
<400> 1283
ugagaaugag ccucgauaa 19
<210> 1284
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent ense strand
<400> 1284
gccccuuauu guuauacg 18
<210> 1285
<211> 18
<212> RNA
<213> artificial sequence
<220>
<223> LPA RNAi agent ense strand
<400> 1285
uuaucgaggc ucauucuc 18
Claims (31)
- 센스 가닥 및 안티센스 가닥을 포함하는 LPA RNA 간섭(RNAi) 물질이며,
상기 안티센스 가닥이
a) 서열 번호 1-108 중 임의의 것의 2-19번 뉴클레오타이드, 또는
b) 표 1 또는 표 2A의 임의의 안티센스 가닥
의 뉴클레오타이드 서열을 포함하는 것인 LPA RNAi 물질. - 제1항에 있어서, 상기 센스 가닥이
a) 서열 번호 190-268 중 임의의 것의 1-19번 뉴클레오타이드, 또는
b) 표 1 또는 표 2B의 임의의 센스 가닥
의 뉴클레오타이드 서열을 포함하는 것인 LPA RNAi 물질. - 제1항에 있어서, 상기 안티센스 가닥이 서열 번호 1246, 서열 번호 1242, 서열 번호 1244, 서열 번호 1248, 서열 번호 1250, 서열 번호 1252, 또는 서열 번호 1254, 서열 번호 1280, 서열 번호 1281, 서열 번호 1282 또는 서열 번호 1283 중 임의의 것의 뉴클레오타이드 서열을 포함하는 것인 LPA RNAi 물질.
- 제3항에 있어서,
a) 상기 안티센스 가닥이 서열 번호 1246의 뉴클레오타이드 서열을 포함하고, 상기 센스 가닥이 서열 번호 1247의 뉴클레오타이드 서열을 포함하거나,
b) 상기 안티센스 가닥이 서열 번호 1242의 뉴클레오타이드 서열을 포함하고, 상기 센스 가닥이 서열 번호 1243의 뉴클레오타이드 서열을 포함하거나,
c) 상기 안티센스 가닥이 서열 번호 1244의 뉴클레오타이드 서열을 포함하고, 상기 센스 가닥이 서열 번호 1245의 뉴클레오타이드 서열을 포함하거나,
d) 상기 안티센스 가닥이 서열 번호 1248의 뉴클레오타이드 서열을 포함하고, 상기 센스 가닥이 서열 번호 1249의 뉴클레오타이드 서열을 포함하거나,
e) 상기 안티센스 가닥이 서열 번호 1250의 뉴클레오타이드 서열을 포함하고, 상기 센스 가닥이 서열 번호 1251의 뉴클레오타이드 서열을 포함하거나,
f) 상기 안티센스 가닥이 서열 번호 1252의 뉴클레오타이드 서열을 포함하고, 상기 센스 가닥이 서열 번호 1253의 뉴클레오타이드 서열을 포함하거나,
g) 상기 안티센스 가닥이 서열 번호 1254의 뉴클레오타이드 서열을 포함하고, 상기 센스 가닥이 서열 번호 1255의 뉴클레오타이드 서열을 포함하거나,
h) 상기 안티센스 가닥이 서열 번호 1280의 뉴클레오타이드 서열을 포함하고, 상기 센스 가닥이 서열 번호 1260의 뉴클레오타이드 서열을 포함하거나,
i) 상기 안티센스 가닥이 서열 번호 1281의 뉴클레오타이드 서열을 포함하고, 상기 센스 가닥이 서열 번호 1258의 뉴클레오타이드 서열을 포함하거나,
j) 상기 안티센스 가닥이 서열 번호 1280의 뉴클레오타이드 서열을 포함하고, 상기 센스 가닥이 서열 번호 1284의 뉴클레오타이드 서열을 포함하거나,
k) 상기 안티센스 가닥이 서열 번호 1281의 뉴클레오타이드 서열을 포함하고, 상기 센스 가닥이 서열 번호 1285의 뉴클레오타이드 서열을 포함하거나,
l) 상기 안티센스 가닥이 서열 번호 1282의 뉴클레오타이드 서열을 포함하고, 상기 센스 가닥이 서열 번호 1259의 뉴클레오타이드 서열을 포함하거나,
m) 상기 안티센스 가닥이 서열 번호 1283의 뉴클레오타이드 서열을 포함하고, 상기 센스 가닥이 서열 번호 1249의 뉴클레오타이드 서열을 포함
하는 것인 LPA RNAi 물질. - 제1항 내지 제4항 중 어느 한 항에 있어서, 상기 센스 가닥 및/또는 상기 안티센스 가닥이 1개 내지 6개 뉴클레오타이드 길이의 3' 및/또는 5' 연장을 추가로 포함하는 것인 LPA RNAi 물질.
- 제1항 내지 제5항 중 어느 한 항에 있어서, 상기 안티센스 가닥이 서열 번호 156, 서열 번호 164 또는 서열 번호 188 중 임의의 것의 뉴클레오타이드 서열을 포함하는 것인 LPA RNAi 물질.
- 제6항에 있어서,
a) 상기 안티센스 가닥이 서열 번호 156의 뉴클레오타이드 서열을 포함하고, 상기 센스 가닥이 서열 번호 310의 뉴클레오타이드 서열을 포함하거나,
b) 상기 안티센스 가닥이 서열 번호 164의 뉴클레오타이드 서열을 포함하고, 상기 센스 가닥이 서열 번호 357의 뉴클레오타이드 서열을 포함하거나,
c) 상기 안티센스 가닥이 서열 번호 188의 뉴클레오타이드 서열을 포함하고, 상기 센스 가닥이 서열 번호 384의 뉴클레오타이드 서열을 포함하거나,
d) 상기 안티센스 가닥이 서열 번호 164의 뉴클레오타이드 서열을 포함하고, 상기 센스 가닥이 서열 번호 376의 뉴클레오타이드 서열을 포함하거나,
e) 상기 안티센스 가닥이 서열 번호 164의 뉴클레오타이드 서열을 포함하고, 상기 센스 가닥이 서열 번호 384의 뉴클레오타이드 서열을 포함
하는 것인 LPA RNAi 물질. - 제1항 내지 제7항 중 어느 한 항에 있어서, 상기 센스 가닥 및/또는 상기 안티센스 가닥이 독립적으로 하나 이상의 변형된 뉴클레오타이드를 포함하는 것인 LPA RNAi 물질.
- 제8항에 있어서, 상기 하나 이상의 변형된 뉴클레오타이드가 독립적으로 2'-O-메틸 변형된 뉴클레오타이드, 5'-포스포로티오에이트기를 포함하는 뉴클레오타이드, 2'-데옥시-2'-플루오로 변형된 뉴클레오타이드, 2'-데옥시 변형된 뉴클레오타이드, 잠긴(locked) 뉴클레오타이드, 비염기성 뉴클레오타이드, 데옥시타이미딘, 인버티드(inverted) 데옥시타이미딘, 2'-아미노 변형된 뉴클레오타이드, 2'-알킬 변형된 뉴클레오타이드, 모르폴리노 뉴클레오타이드 및 뉴클레오타이드를 포함하는 비천연 염기로 이루어진 군으로부터 선택된 것인 LPA RNAi 물질.
- 제1항 내지 제9항 중 어느 한 항에 있어서, 하나 이상의 포스포로티오에이트 뉴클레오사이드간 연결을 포함하는 LPA RNAi 물질.
- 제1항 내지 제10항 중 어느 한 항에 있어서, 표적화기를 추가로 포함하는 LPA RNAi 물질.
- 제11항에 있어서, 상기 표적화기가 아시알로당단백질 수용체 리간드를 포함하는 것인 LPA RNAi 물질.
- 제12항에 있어서, 상기 아시알로당단백질 수용체 리간드가 갈락토스 클러스터를 포함하는 것인 LPA RNAi 물질.
- 제13항에 있어서, 상기 갈락토스 클러스터가 (C11-PEG3-NAG3), (C11-PEG3-NAG3), (C6-PEG4-NAG3), (NAG3), (NAG4), (NAG3-AA2), (NAG3-Palm), (NAG13), (NAG18), (NAG24), (NAG25), (NAG25)s, (NAG26), (NAG27), (NAG28), (NAG29), (NAG30), (NAG30)s, (NAG31), (NAG13), (NAG31s), (NAG32), (NAG33), (NAG34), (NAG35), (NAG36) 및 (NAG37)로 이루어진 군으로부터 선택된 것인 LPA RNAi 물질.
- 제11항 내지 제14항 중 어느 한 항에 있어서, 상기 표적화기가 상기 센스 가닥에 접합된 것인 LPA RNAi 물질.
- 제15항에 있어서, 상기 표적화기가 상기 센스 가닥의 5' 말단에 접합된 것인 LPA RNAi 물질.
- 제15항에 있어서, 상기 표적화기가 상기 센스 가닥의 3' 말단에 접합된 것인 LPA RNAi 물질.
- 제1항 내지 제17항 중 어느 한 항에 있어서, 연결기를 추가로 포함하는 LPA RNAi 물질.
- 제1항 내지 제18항 중 어느 한 항에 있어서, 1개 또는 2개의 오버행(overhang)을 포함하는 LPA RNAi 물질.
- 제1항 내지 제18항 중 어느 한 항에 있어서, 1개 또는 2개의 날카로운 말단(frayed end)을 포함하는 LPA RNAi 물질.
- 제1항 내지 제18항 중 어느 한 항에 있어서, 1개 또는 2개의 무딘 말단(blunt end)을 포함하는 LPA RNAi 물질.
- 제1항 내지 제18항 중 어느 한 항에 있어서, 표 3A 또는 표 3B에서의 임의의 듀플렉스 서열을 포함하는 LPA RNAi 물질.
- 제1항 내지 제18항 중 어느 한 항에 있어서, AD03460, AD03536, AD03581, AD03583, AD3847 또는 AD04110을 포함하는 LPA RNAi 물질.
- 약제의 제조를 위한, 제1항 내지 제22항 중 어느 한 항의 LPA RNAi 물질의 용도.
- 제1항 내지 제23항 중 어느 한 항에 있어서, 하나 이상의 추가 치유제 또는 치료제를 추가로 포함하는 LPA RNAi 물질.
- 제1항 내지 제23항 중 어느 한 항에 있어서, 약제학적으로 허용가능한 부형제를 추가로 포함하는 LPA RNAi 물질.
- 제1항 내지 제23항 중 어느 한 항에 있어서, 키트, 용기, 팩, 분배기, 프리필드(pre-filled) 주사기 또는 바이알에 포장된 LPA RNAi 물질.
- 세포, 조직 또는 대상체에서 LPA 발현을 저해하는 방법이며, 제1항 내지 제26항 중 어느 한 항의 LPA RNAi 물질의 치료학적 유효량을 상기 대상체에게 투여하는 것을 포함하는, 세포, 조직 또는 대상체에서 LPA 발현을 저해하는 방법.
- 제27항에 있어서, 상기 조성물이 비경구로 투여되는 것인 방법.
- 제27항 또는 제28항에 있어서, 상기 세포가 간세포인 방법.
- 센스 서열 및 안티센스 서열을 포함하는 LPA RNA 간섭(RNAi) 물질이며,
상기 안티센스 서열이 표 1 또는 표 2A의 임의의 안티센스 서열의 1-17번, 2-18번, 1-19번, 2-19번, 1-21번, 1-23번 또는 1-26번 뉴클레오타이드의 뉴클레오타이드 서열을 포함하는 것인 LPA RNAi 물질.
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562235816P | 2015-10-01 | 2015-10-01 | |
| US62/235,816 | 2015-10-01 | ||
| US201662346304P | 2016-06-06 | 2016-06-06 | |
| US62/346,304 | 2016-06-06 | ||
| US201662383221P | 2016-09-02 | 2016-09-02 | |
| US62/383,221 | 2016-09-02 | ||
| PCT/US2016/054729 WO2017059223A2 (en) | 2015-10-01 | 2016-09-30 | Compositions and methods for inhibiting gene expression of lpa |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20180052703A true KR20180052703A (ko) | 2018-05-18 |
Family
ID=58424351
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020187010095A KR20180052703A (ko) | 2015-10-01 | 2016-09-30 | Lpa의 유전자 발현을 저해하기 위한 조성물 및 방법 |
Country Status (37)
| Country | Link |
|---|---|
| US (3) | US9932586B2 (ko) |
| EP (2) | EP3356529B1 (ko) |
| JP (4) | JP6991966B2 (ko) |
| KR (1) | KR20180052703A (ko) |
| CN (1) | CN108368506A (ko) |
| AU (2) | AU2016331084B2 (ko) |
| BR (1) | BR112018006489A2 (ko) |
| CA (1) | CA3000397A1 (ko) |
| CL (1) | CL2018000803A1 (ko) |
| CO (1) | CO2018003678A2 (ko) |
| CR (1) | CR20180231A (ko) |
| CY (1) | CY1125263T1 (ko) |
| DK (1) | DK3356529T3 (ko) |
| EA (1) | EA038478B1 (ko) |
| ES (1) | ES2896298T3 (ko) |
| HK (1) | HK1259063A1 (ko) |
| HR (1) | HRP20211410T1 (ko) |
| HU (1) | HUE055942T2 (ko) |
| IL (3) | IL300438A (ko) |
| JO (2) | JOP20210043A1 (ko) |
| LT (1) | LT3356529T (ko) |
| MA (1) | MA43347B1 (ko) |
| MX (2) | MX2018003833A (ko) |
| MY (1) | MY195796A (ko) |
| PE (1) | PE20181139A1 (ko) |
| PH (1) | PH12018500713A1 (ko) |
| PL (1) | PL3356529T3 (ko) |
| PT (1) | PT3356529T (ko) |
| RS (1) | RS62523B1 (ko) |
| SG (1) | SG10202008530TA (ko) |
| SI (1) | SI3356529T1 (ko) |
| TN (1) | TN2018000094A1 (ko) |
| TW (1) | TWI784934B (ko) |
| UA (1) | UA121998C2 (ko) |
| UY (1) | UY36926A (ko) |
| WO (1) | WO2017059223A2 (ko) |
| ZA (1) | ZA202106265B (ko) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7718133B2 (en) | 2003-10-09 | 2010-05-18 | 3M Innovative Properties Company | Multilayer processing devices and methods |
| UY37146A (es) * | 2016-03-07 | 2017-09-29 | Arrowhead Pharmaceuticals Inc | Ligandos de direccionamiento para compuestos terapéuticos |
| KR102557906B1 (ko) * | 2016-09-02 | 2023-07-20 | 애로우헤드 파마슈티컬스 인코포레이티드 | 표적화 리간드 |
| WO2018185241A1 (en) | 2017-04-05 | 2018-10-11 | Silence Therapeutics Gmbh | Products and compositions |
| KR20200024793A (ko) * | 2017-07-06 | 2020-03-09 | 애로우헤드 파마슈티컬스 인코포레이티드 | 알파-ENaC의 발현을 억제하기 위한 RNAi 작용제 및 사용 방법 |
| CN111107853A (zh) * | 2017-09-11 | 2020-05-05 | 箭头药业股份有限公司 | 用于抑制载脂蛋白C-III (APOC3)的表达的RNAi试剂和组合物 |
| TN2020000038A1 (en) * | 2017-09-14 | 2021-10-04 | Arrowhead Pharmaceuticals Inc | Rnai agents and compositions for inhibiting expression of angiopoietin-like 3 (angptl3), and methods of use |
| EP3697909A4 (en) * | 2017-10-17 | 2021-10-13 | Arrowhead Pharmaceuticals, Inc. | RNAI-BASED AGENTS AND COMPOSITIONS INTENDED TO INHIBIT ASIALOGLYCOPROTEIN RECEPTOR 1 EXPRESSION |
| EP3483270A1 (en) * | 2017-11-13 | 2019-05-15 | Silence Therapeutics GmbH | Products and compositions |
| RS63955B1 (sr) * | 2017-11-13 | 2023-02-28 | Silence Therapeutics Gmbh | Nukleinske kiseline za inhibiciju ekspresije lpa u ćeliji |
| AU2019342117A1 (en) * | 2018-09-19 | 2021-03-04 | Arrowhead Pharmaceuticals, Inc. | RNAi agents for inhibiting expression of 17beta-HSD type 13- (HSD17B13), compositions thereof, and methods of use |
| PL3880818T3 (pl) * | 2018-11-13 | 2023-01-23 | Silence Therapeutics Gmbh | Kwasy nukleinowe do hamowania ekspresji LPA w komórce |
| AU2020399636A1 (en) | 2019-12-09 | 2022-06-02 | Amgen Inc. | RNAi constructs and methods for inhibiting LPA expression |
| JP7476422B2 (ja) | 2020-08-05 | 2024-04-30 | ディセルナ ファーマシューティカルズ インコーポレイテッド | Ｌｐａ発現を阻害するための組成物及び方法 |
| JP2023545502A (ja) * | 2020-10-16 | 2023-10-30 | サノフイ | リポタンパク質（ａ）を阻害するためのｒｎａ組成物および方法 |
| MX2023005198A (es) | 2020-11-05 | 2023-05-16 | Amgen Inc | Metodos para tratar la enfermedad cardiovascular aterosclerotica con constructos de iarn dirigidos a lpa. |
| WO2022121959A1 (zh) * | 2020-12-09 | 2022-06-16 | 纳肽得有限公司 | siRNA分子及其在治疗冠状动脉疾病中的应用 |
| EP4237561A1 (en) | 2020-12-23 | 2023-09-06 | Argonaute Rna Limited | Treatment of cardiovascular disease |
| WO2022266316A1 (en) | 2021-06-18 | 2022-12-22 | Hongene Biotech Corporation | Functionalized n-acetylgalactosamine nucleosides |
| US11692001B2 (en) | 2021-08-30 | 2023-07-04 | Hongene Biotech Corporation | Functionalized n-acetylgalactosamine analogs |
| CA3229020A1 (en) | 2021-09-14 | 2023-03-23 | Stella PELENGARIS | Treatment of cardiovascular disease |
| CN116801886A (zh) * | 2021-09-18 | 2023-09-22 | 上海金中锘美生物医药科技有限公司 | Lpa抑制剂及其用途 |
| WO2023114746A1 (en) | 2021-12-15 | 2023-06-22 | Hongene Biotech Corporation | Functionalized n-acetylgalactosamine analogs |
| CN114703184A (zh) * | 2022-03-11 | 2022-07-05 | 厦门甘宝利生物医药有限公司 | Lpa抑制剂及其用途 |
| WO2024032681A1 (zh) * | 2022-08-11 | 2024-02-15 | 益杰立科(上海)生物科技有限公司 | 一种表观编辑靶点的方法及用途 |
| CN115851723B (zh) * | 2022-10-24 | 2023-10-03 | 厦门甘宝利生物医药有限公司 | 一种抑制lpa基因表达的rna抑制剂及其应用 |
Family Cites Families (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL9201440A (nl) | 1992-08-11 | 1994-03-01 | Univ Leiden | Triantennaire clusterglycosiden, hun bereiding en toepassing. |
| US5599706A (en) | 1994-09-23 | 1997-02-04 | Stinchcomb; Dan T. | Ribozymes targeted to apo(a) mRNA |
| JP2002537828A (ja) | 1999-03-10 | 2002-11-12 | フォゲン リミティド | 細胞への物質のデリバリー |
| ES2215494T5 (es) * | 2000-12-01 | 2017-12-28 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Moléculas de RNA pequeñas que median la interferencia de RNA |
| US7259150B2 (en) | 2001-08-07 | 2007-08-21 | Isis Pharmaceuticals, Inc. | Modulation of apolipoprotein (a) expression |
| US7227014B2 (en) | 2001-08-07 | 2007-06-05 | Isis Pharmaceuticals, Inc. | Antisense modulation of apolipoprotein (a) expression |
| DE602004027798D1 (de) | 2003-03-12 | 2010-08-05 | Univ Arizona State | Verfahren zur regulierung von angiogenese mit apelin-zusammensetzungen |
| EP2514758B2 (en) | 2004-03-15 | 2021-06-23 | City of Hope | Methods and compositions for the specific inhibition of gene expression by double-stranded RNA |
| CN102614528B (zh) * | 2006-08-18 | 2014-02-26 | 箭头研究公司 | 用于体内递送多核苷酸的多缀合物 |
| CN102325534B (zh) | 2008-12-18 | 2016-02-17 | 戴瑟纳制药公司 | 延长的dicer酶底物和特异性抑制基因表达的方法 |
| WO2010093788A2 (en) | 2009-02-11 | 2010-08-19 | Dicerna Pharmaceuticals, Inc. | Multiplex dicer substrate rna interference molecules having joining sequences |
| SI2539451T1 (sl) | 2010-02-24 | 2016-04-29 | Arrowhead Research Corporation | Sestavki za ciljano dostavo sirna |
| US8865675B2 (en) * | 2010-05-12 | 2014-10-21 | Protiva Biotherapeutics, Inc. | Compositions and methods for silencing apolipoprotein B |
| US8501930B2 (en) * | 2010-12-17 | 2013-08-06 | Arrowhead Madison Inc. | Peptide-based in vivo siRNA delivery system |
| RU2013117288A (ru) | 2010-12-17 | 2015-01-27 | Эрроухэд Рисерч Корпорейшн | СОДЕРЖАЩАЯ ГАЛАКТОЗНЫЙ КЛАСТЕР НАЦЕЛИВАЮЩАЯ ГРУППА ДЛЯ миРНК, МОДУЛИРУЮЩАЯ ФОРМАКОКИНЕТИЧЕСКИЕ СВОЙСТВА |
| MX341118B (es) | 2010-12-29 | 2016-08-09 | Arrowhead Res Corp | Cojugados de suministro de polinucleotidos in vivo que tienen acoplamientos sensibles a enzima. |
| BR112014004585A2 (pt) | 2011-08-26 | 2017-06-13 | Arrowhead Res Corp | polímeros de poli(éster vinílico) para liberação de ácido nucleico in vivo |
| PL3301177T3 (pl) * | 2011-11-18 | 2020-08-24 | Alnylam Pharmaceuticals, Inc. | ŚRODKI RNAi, KOMPOZYCJE I SPOSOBY ICH ZASTOSOWANIA DO LECZENIA CHORÓB ZWIĄZANYCH Z TRANSTYRETYNĄ (TTR) |
| WO2013158141A1 (en) | 2012-04-18 | 2013-10-24 | Arrowhead Research Corporation | Poly(acrylate) polymers for in vivo nucleic acid delivery |
| EP2855500B1 (en) | 2012-05-24 | 2020-07-01 | Ionis Pharmaceuticals, Inc. | Methods and compositions for modulating apolipoprotein(a) expression |
| JP6387084B2 (ja) | 2013-05-01 | 2018-09-05 | アイオーニス ファーマシューティカルズ， インコーポレーテッドＩｏｎｉｓ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ，Ｉｎｃ． | アポリポタンパク質ｃ−ｉｉｉの発現を調節するための組成物および方法 |
| WO2016149020A1 (en) * | 2015-03-17 | 2016-09-22 | Arrowhead Research Corporation | Rna interference agents |
| KR20180011198A (ko) | 2015-05-29 | 2018-01-31 | 애로우헤드 파마슈티컬스 인코포레이티드 | ＨＩＦ２α의 유전자 발현을 억제하는 조성물 및 방법 |
| DK3329002T3 (da) * | 2015-07-31 | 2021-01-11 | Alnylam Pharmaceuticals Inc | Transthyretin (ttr)-irna-sammensætninger og fremgangsmåder til anvendelse deraf til behandling eller forebyggelse af ttr-forbundne sygdomme |
| UY37146A (es) | 2016-03-07 | 2017-09-29 | Arrowhead Pharmaceuticals Inc | Ligandos de direccionamiento para compuestos terapéuticos |
-
2015
- 2015-10-01 JO JOP/2021/0043A patent/JOP20210043A1/ar unknown
-
2016
- 2016-09-28 JO JOP/2016/0211A patent/JOP20160211B1/ar active
- 2016-09-30 CA CA3000397A patent/CA3000397A1/en active Pending
- 2016-09-30 WO PCT/US2016/054729 patent/WO2017059223A2/en active Application Filing
- 2016-09-30 UA UAA201804593A patent/UA121998C2/uk unknown
- 2016-09-30 EP EP16852695.2A patent/EP3356529B1/en active Active
- 2016-09-30 JP JP2018516738A patent/JP6991966B2/ja active Active
- 2016-09-30 PE PE2018000487A patent/PE20181139A1/es unknown
- 2016-09-30 DK DK16852695.2T patent/DK3356529T3/da active
- 2016-09-30 AU AU2016331084A patent/AU2016331084B2/en active Active
- 2016-09-30 PT PT168526952T patent/PT3356529T/pt unknown
- 2016-09-30 PL PL16852695T patent/PL3356529T3/pl unknown
- 2016-09-30 TN TNP/2018/000094A patent/TN2018000094A1/en unknown
- 2016-09-30 SG SG10202008530TA patent/SG10202008530TA/en unknown
- 2016-09-30 IL IL300438A patent/IL300438A/en unknown
- 2016-09-30 HR HRP20211410TT patent/HRP20211410T1/hr unknown
- 2016-09-30 SI SI201631374T patent/SI3356529T1/sl unknown
- 2016-09-30 EP EP21191363.7A patent/EP4029941A1/en active Pending
- 2016-09-30 UY UY0001036926A patent/UY36926A/es unknown
- 2016-09-30 RS RS20211351A patent/RS62523B1/sr unknown
- 2016-09-30 BR BR112018006489-0A patent/BR112018006489A2/pt active Search and Examination
- 2016-09-30 US US15/281,309 patent/US9932586B2/en active Active
- 2016-09-30 CR CR20180231A patent/CR20180231A/es unknown
- 2016-09-30 ES ES16852695T patent/ES2896298T3/es active Active
- 2016-09-30 MX MX2018003833A patent/MX2018003833A/es unknown
- 2016-09-30 HU HUE16852695A patent/HUE055942T2/hu unknown
- 2016-09-30 LT LTEPPCT/US2016/054729T patent/LT3356529T/lt unknown
- 2016-09-30 MY MYPI2018000440A patent/MY195796A/en unknown
- 2016-09-30 KR KR1020187010095A patent/KR20180052703A/ko not_active Application Discontinuation
- 2016-09-30 EA EA201890864A patent/EA038478B1/ru unknown
- 2016-09-30 TW TW105131823A patent/TWI784934B/zh active
- 2016-09-30 CN CN201680057095.8A patent/CN108368506A/zh active Pending
-
2017
- 2017-04-06 MA MA43347A patent/MA43347B1/fr unknown
-
2018
- 2018-02-21 US US15/901,810 patent/US10662427B2/en active Active
- 2018-03-25 IL IL258333A patent/IL258333B/en unknown
- 2018-03-27 MX MX2022013010A patent/MX2022013010A/es unknown
- 2018-03-28 CL CL2018000803A patent/CL2018000803A1/es unknown
- 2018-03-28 PH PH12018500713A patent/PH12018500713A1/en unknown
- 2018-04-05 CO CONC2018/0003678A patent/CO2018003678A2/es unknown
-
2019
- 2019-01-29 HK HK19101563.4A patent/HK1259063A1/zh unknown
-
2020
- 2020-05-06 US US16/867,925 patent/US20200263179A1/en active Pending
-
2021
- 2021-03-12 JP JP2021039949A patent/JP7116212B2/ja active Active
- 2021-08-30 ZA ZA2021/06265A patent/ZA202106265B/en unknown
- 2021-11-08 CY CY20211100962T patent/CY1125263T1/el unknown
-
2022
- 2022-02-13 IL IL290566A patent/IL290566B2/en unknown
- 2022-06-15 JP JP2022096415A patent/JP7442574B2/ja active Active
- 2022-12-05 AU AU2022283623A patent/AU2022283623A1/en active Pending
-
2023
- 2023-11-27 JP JP2023199857A patent/JP2024009262A/ja active Pending
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2016331084B2 (en) | Compositions and methods for inhibiting gene expression of LPA | |
| TWI823866B (zh) | 用於抑制類血管生成素蛋白-3(ANGPTL3)表現的RNAi藥劑及組合物及使用方法 | |
| TWI811238B (zh) | 用於抑制脂蛋白元C-III(APOC3)表現之RNAi試劑及組合物 | |
| CN108064313B (zh) | 用于抑制因子xii的基因表达的组合物和方法 | |
| JP2022501040A (ja) | １７β−ＨＳＤ１３型（ＨＳＤ１７Ｂ１３）の発現を阻害するためのＲＮＡｉ剤、その組成物、および使用方法 | |
| JP7473472B2 (ja) | アシアロ糖タンパク質受容体１の発現を阻害するためのＲＮＡｉ剤および組成物 | |
| WO2022271573A1 (en) | Rnai agents for inhibiting expression of xanthine dehydrogenase (xdh), pharmaceutical compositions thereof, and methods of use | |
| TWI836693B (zh) | 抑制ｌｐａ之基因表現之組合物及方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| E902 | Notification of reason for refusal |