CA2897941A1 - Signal-sensor polynucleotides for the alteration of cellular phenotypes - Google Patents
Signal-sensor polynucleotides for the alteration of cellular phenotypes Download PDFInfo
- Publication number
- CA2897941A1 CA2897941A1 CA2897941A CA2897941A CA2897941A1 CA 2897941 A1 CA2897941 A1 CA 2897941A1 CA 2897941 A CA2897941 A CA 2897941A CA 2897941 A CA2897941 A CA 2897941A CA 2897941 A1 CA2897941 A1 CA 2897941A1
- Authority
- CA
- Canada
- Prior art keywords
- cancer
- sensor
- signal
- sensor polynucleotide
- synthetic signal
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 102000040430 polynucleotide Human genes 0.000 title claims abstract description 382
- 108091033319 polynucleotide Proteins 0.000 title claims abstract description 382
- 239000002157 polynucleotide Substances 0.000 title claims abstract description 380
- 230000001413 cellular effect Effects 0.000 title description 19
- 230000004075 alteration Effects 0.000 title description 7
- 238000000034 method Methods 0.000 claims abstract description 71
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 223
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 207
- 229920001184 polypeptide Polymers 0.000 claims description 183
- 150000007523 nucleic acids Chemical group 0.000 claims description 132
- 102000039446 nucleic acids Human genes 0.000 claims description 122
- 108020004707 nucleic acids Proteins 0.000 claims description 122
- 108020004999 messenger RNA Proteins 0.000 claims description 113
- 125000003729 nucleotide group Chemical group 0.000 claims description 107
- 239000002773 nucleotide Substances 0.000 claims description 106
- 230000006907 apoptotic process Effects 0.000 claims description 93
- 210000004027 cell Anatomy 0.000 claims description 91
- 230000027455 binding Effects 0.000 claims description 83
- 239000002679 microRNA Substances 0.000 claims description 77
- 108700011259 MicroRNAs Proteins 0.000 claims description 76
- 206010028980 Neoplasm Diseases 0.000 claims description 69
- 201000011510 cancer Diseases 0.000 claims description 69
- 108020005345 3' Untranslated Regions Proteins 0.000 claims description 57
- 108020004705 Codon Proteins 0.000 claims description 49
- 230000014509 gene expression Effects 0.000 claims description 49
- 108091023045 Untranslated Region Proteins 0.000 claims description 43
- 239000002777 nucleoside Substances 0.000 claims description 38
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 37
- 230000004048 modification Effects 0.000 claims description 30
- 238000012986 modification Methods 0.000 claims description 30
- 210000001519 tissue Anatomy 0.000 claims description 30
- 201000010099 disease Diseases 0.000 claims description 29
- 238000013519 translation Methods 0.000 claims description 26
- 125000003835 nucleoside group Chemical group 0.000 claims description 25
- 108700026244 Open Reading Frames Proteins 0.000 claims description 22
- 238000007385 chemical modification Methods 0.000 claims description 17
- 230000001965 increasing effect Effects 0.000 claims description 17
- 150000003833 nucleoside derivatives Chemical class 0.000 claims description 15
- 230000008859 change Effects 0.000 claims description 13
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 12
- UVBYMVOUBXYSFV-XUTVFYLZSA-N 1-methylpseudouridine Chemical compound O=C1NC(=O)N(C)C=C1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 UVBYMVOUBXYSFV-XUTVFYLZSA-N 0.000 claims description 10
- UVBYMVOUBXYSFV-UHFFFAOYSA-N 1-methylpseudouridine Natural products O=C1NC(=O)N(C)C=C1C1C(O)C(O)C(CO)O1 UVBYMVOUBXYSFV-UHFFFAOYSA-N 0.000 claims description 10
- 229940029575 guanosine Drugs 0.000 claims description 10
- 210000000056 organ Anatomy 0.000 claims description 10
- 108700028146 Genetic Enhancer Elements Proteins 0.000 claims description 9
- 230000030833 cell death Effects 0.000 claims description 9
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 8
- 208000035475 disorder Diseases 0.000 claims description 8
- 238000011282 treatment Methods 0.000 claims description 8
- ZAYHVCMSTBRABG-UHFFFAOYSA-N 5-Methylcytidine Natural products O=C1N=C(N)C(C)=CN1C1C(O)C(O)C(CO)O1 ZAYHVCMSTBRABG-UHFFFAOYSA-N 0.000 claims description 7
- ZAYHVCMSTBRABG-JXOAFFINSA-N 5-methylcytidine Chemical compound O=C1N=C(N)C(C)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 ZAYHVCMSTBRABG-JXOAFFINSA-N 0.000 claims description 7
- 208000002193 Pain Diseases 0.000 claims description 7
- 210000000214 mouth Anatomy 0.000 claims description 7
- 208000024891 symptom Diseases 0.000 claims description 7
- 206010027476 Metastases Diseases 0.000 claims description 6
- 210000001072 colon Anatomy 0.000 claims description 6
- 230000001419 dependent effect Effects 0.000 claims description 6
- 239000000499 gel Substances 0.000 claims description 6
- 230000009401 metastasis Effects 0.000 claims description 6
- 206010006187 Breast cancer Diseases 0.000 claims description 5
- 208000026310 Breast neoplasm Diseases 0.000 claims description 5
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 5
- 206010009944 Colon cancer Diseases 0.000 claims description 5
- 206010060862 Prostate cancer Diseases 0.000 claims description 5
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 5
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 5
- 201000010881 cervical cancer Diseases 0.000 claims description 5
- 208000006990 cholangiocarcinoma Diseases 0.000 claims description 5
- 208000029742 colonic neoplasm Diseases 0.000 claims description 5
- 238000002347 injection Methods 0.000 claims description 5
- 239000007924 injection Substances 0.000 claims description 5
- 230000004614 tumor growth Effects 0.000 claims description 5
- JRYMOPZHXMVHTA-DAGMQNCNSA-N 2-amino-7-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1h-pyrrolo[2,3-d]pyrimidin-4-one Chemical compound C1=CC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O JRYMOPZHXMVHTA-DAGMQNCNSA-N 0.000 claims description 4
- BGTXMQUSDNMLDW-AEHJODJJSA-N 2-amino-9-[(2r,3s,4r,5r)-3-fluoro-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-3h-purin-6-one Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](CO)[C@@H](O)[C@]1(O)F BGTXMQUSDNMLDW-AEHJODJJSA-N 0.000 claims description 4
- HCAJQHYUCKICQH-VPENINKCSA-N 8-Oxo-7,8-dihydro-2'-deoxyguanosine Chemical compound C1=2NC(N)=NC(=O)C=2NC(=O)N1[C@H]1C[C@H](O)[C@@H](CO)O1 HCAJQHYUCKICQH-VPENINKCSA-N 0.000 claims description 4
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims description 4
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 claims description 4
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 4
- 206010061424 Anal cancer Diseases 0.000 claims description 4
- 208000007860 Anus Neoplasms Diseases 0.000 claims description 4
- 208000032467 Aplastic anaemia Diseases 0.000 claims description 4
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 4
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims description 4
- 206010004593 Bile duct cancer Diseases 0.000 claims description 4
- 206010005003 Bladder cancer Diseases 0.000 claims description 4
- 206010005949 Bone cancer Diseases 0.000 claims description 4
- 208000018084 Bone neoplasm Diseases 0.000 claims description 4
- 206010007279 Carcinoid tumour of the gastrointestinal tract Diseases 0.000 claims description 4
- 208000005024 Castleman disease Diseases 0.000 claims description 4
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims description 4
- 206010014733 Endometrial cancer Diseases 0.000 claims description 4
- 206010014759 Endometrial neoplasm Diseases 0.000 claims description 4
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 4
- 208000012468 Ewing sarcoma/peripheral primitive neuroectodermal tumor Diseases 0.000 claims description 4
- 208000022072 Gallbladder Neoplasms Diseases 0.000 claims description 4
- 206010051066 Gastrointestinal stromal tumour Diseases 0.000 claims description 4
- 208000017604 Hodgkin disease Diseases 0.000 claims description 4
- 208000021519 Hodgkin lymphoma Diseases 0.000 claims description 4
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims description 4
- 206010021042 Hypopharyngeal cancer Diseases 0.000 claims description 4
- 206010056305 Hypopharyngeal neoplasm Diseases 0.000 claims description 4
- 229930010555 Inosine Natural products 0.000 claims description 4
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 claims description 4
- 208000007766 Kaposi sarcoma Diseases 0.000 claims description 4
- 206010023825 Laryngeal cancer Diseases 0.000 claims description 4
- 108091026898 Leader sequence (mRNA) Proteins 0.000 claims description 4
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims description 4
- 206010025323 Lymphomas Diseases 0.000 claims description 4
- 208000032271 Malignant tumor of penis Diseases 0.000 claims description 4
- 208000034578 Multiple myelomas Diseases 0.000 claims description 4
- 201000003793 Myelodysplastic syndrome Diseases 0.000 claims description 4
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims description 4
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 4
- 208000033833 Myelomonocytic Chronic Leukemia Diseases 0.000 claims description 4
- 208000001894 Nasopharyngeal Neoplasms Diseases 0.000 claims description 4
- 206010061306 Nasopharyngeal cancer Diseases 0.000 claims description 4
- 206010029260 Neuroblastoma Diseases 0.000 claims description 4
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 4
- 206010031096 Oropharyngeal cancer Diseases 0.000 claims description 4
- 206010057444 Oropharyngeal neoplasm Diseases 0.000 claims description 4
- 206010033128 Ovarian cancer Diseases 0.000 claims description 4
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 4
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 4
- 208000002471 Penile Neoplasms Diseases 0.000 claims description 4
- 206010034299 Penile cancer Diseases 0.000 claims description 4
- 208000007913 Pituitary Neoplasms Diseases 0.000 claims description 4
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 4
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims description 4
- 208000015634 Rectal Neoplasms Diseases 0.000 claims description 4
- 208000006265 Renal cell carcinoma Diseases 0.000 claims description 4
- 201000000582 Retinoblastoma Diseases 0.000 claims description 4
- 208000004337 Salivary Gland Neoplasms Diseases 0.000 claims description 4
- 206010061934 Salivary gland cancer Diseases 0.000 claims description 4
- 206010039491 Sarcoma Diseases 0.000 claims description 4
- 208000000453 Skin Neoplasms Diseases 0.000 claims description 4
- 206010041067 Small cell lung cancer Diseases 0.000 claims description 4
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 4
- 208000024313 Testicular Neoplasms Diseases 0.000 claims description 4
- 206010057644 Testis cancer Diseases 0.000 claims description 4
- 206010043515 Throat cancer Diseases 0.000 claims description 4
- 208000000728 Thymus Neoplasms Diseases 0.000 claims description 4
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 4
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 4
- 206010047741 Vulval cancer Diseases 0.000 claims description 4
- 208000004354 Vulvar Neoplasms Diseases 0.000 claims description 4
- 208000016025 Waldenstroem macroglobulinemia Diseases 0.000 claims description 4
- 208000033559 Waldenström macroglobulinemia Diseases 0.000 claims description 4
- 208000008383 Wilms tumor Diseases 0.000 claims description 4
- 230000001919 adrenal effect Effects 0.000 claims description 4
- 201000011165 anus cancer Diseases 0.000 claims description 4
- 208000026900 bile duct neoplasm Diseases 0.000 claims description 4
- 210000000988 bone and bone Anatomy 0.000 claims description 4
- 208000011654 childhood malignant neoplasm Diseases 0.000 claims description 4
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims description 4
- 201000010902 chronic myelomonocytic leukemia Diseases 0.000 claims description 4
- 230000001054 cortical effect Effects 0.000 claims description 4
- 201000004101 esophageal cancer Diseases 0.000 claims description 4
- 208000024519 eye neoplasm Diseases 0.000 claims description 4
- 206010016256 fatigue Diseases 0.000 claims description 4
- 201000010175 gallbladder cancer Diseases 0.000 claims description 4
- 206010017758 gastric cancer Diseases 0.000 claims description 4
- 201000011243 gastrointestinal stromal tumor Diseases 0.000 claims description 4
- 208000003884 gestational trophoblastic disease Diseases 0.000 claims description 4
- 201000006866 hypopharynx cancer Diseases 0.000 claims description 4
- 230000001939 inductive effect Effects 0.000 claims description 4
- 229960003786 inosine Drugs 0.000 claims description 4
- 206010023841 laryngeal neoplasm Diseases 0.000 claims description 4
- 210000000265 leukocyte Anatomy 0.000 claims description 4
- 201000007270 liver cancer Diseases 0.000 claims description 4
- 208000014018 liver neoplasm Diseases 0.000 claims description 4
- 208000026807 lung carcinoid tumor Diseases 0.000 claims description 4
- 208000006178 malignant mesothelioma Diseases 0.000 claims description 4
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 4
- 201000001441 melanoma Diseases 0.000 claims description 4
- 208000018795 nasal cavity and paranasal sinus carcinoma Diseases 0.000 claims description 4
- 201000008026 nephroblastoma Diseases 0.000 claims description 4
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 4
- 201000008106 ocular cancer Diseases 0.000 claims description 4
- 201000005443 oral cavity cancer Diseases 0.000 claims description 4
- 201000006958 oropharynx cancer Diseases 0.000 claims description 4
- 201000008968 osteosarcoma Diseases 0.000 claims description 4
- 230000036407 pain Effects 0.000 claims description 4
- 201000002528 pancreatic cancer Diseases 0.000 claims description 4
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 4
- 206010038038 rectal cancer Diseases 0.000 claims description 4
- 201000001275 rectum cancer Diseases 0.000 claims description 4
- 201000009410 rhabdomyosarcoma Diseases 0.000 claims description 4
- 208000011571 secondary malignant neoplasm Diseases 0.000 claims description 4
- 201000000849 skin cancer Diseases 0.000 claims description 4
- 208000000587 small cell lung carcinoma Diseases 0.000 claims description 4
- 201000002314 small intestine cancer Diseases 0.000 claims description 4
- 210000004872 soft tissue Anatomy 0.000 claims description 4
- 201000011549 stomach cancer Diseases 0.000 claims description 4
- 201000003120 testicular cancer Diseases 0.000 claims description 4
- 201000009377 thymus cancer Diseases 0.000 claims description 4
- 201000002510 thyroid cancer Diseases 0.000 claims description 4
- 238000011200 topical administration Methods 0.000 claims description 4
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 4
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 4
- 208000037965 uterine sarcoma Diseases 0.000 claims description 4
- 206010046885 vaginal cancer Diseases 0.000 claims description 4
- 208000013139 vaginal neoplasm Diseases 0.000 claims description 4
- 201000005102 vulva cancer Diseases 0.000 claims description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 3
- 206010008399 Change of bowel habit Diseases 0.000 claims description 3
- 206010011224 Cough Diseases 0.000 claims description 3
- 206010013952 Dysphonia Diseases 0.000 claims description 3
- 206010013975 Dyspnoeas Diseases 0.000 claims description 3
- 206010019233 Headaches Diseases 0.000 claims description 3
- 208000032843 Hemorrhage Diseases 0.000 claims description 3
- 208000010473 Hoarseness Diseases 0.000 claims description 3
- 206010023126 Jaundice Diseases 0.000 claims description 3
- 208000003251 Pruritus Diseases 0.000 claims description 3
- 206010037660 Pyrexia Diseases 0.000 claims description 3
- 241000519995 Stachys sylvatica Species 0.000 claims description 3
- 208000007536 Thrombosis Diseases 0.000 claims description 3
- 230000000740 bleeding effect Effects 0.000 claims description 3
- 210000004369 blood Anatomy 0.000 claims description 3
- 239000008280 blood Substances 0.000 claims description 3
- 238000004820 blood count Methods 0.000 claims description 3
- 239000011575 calcium Substances 0.000 claims description 3
- 229910052791 calcium Inorganic materials 0.000 claims description 3
- 208000002173 dizziness Diseases 0.000 claims description 3
- 201000006549 dyspepsia Diseases 0.000 claims description 3
- 230000003779 hair growth Effects 0.000 claims description 3
- 231100000869 headache Toxicity 0.000 claims description 3
- 208000000069 hyperpigmentation Diseases 0.000 claims description 3
- 230000003810 hyperpigmentation Effects 0.000 claims description 3
- 230000005923 long-lasting effect Effects 0.000 claims description 3
- 230000009747 swallowing Effects 0.000 claims description 3
- 230000008719 thickening Effects 0.000 claims description 3
- 208000016261 weight loss Diseases 0.000 claims description 3
- 230000004580 weight loss Effects 0.000 claims description 3
- 239000006071 cream Substances 0.000 claims description 2
- 238000007918 intramuscular administration Methods 0.000 claims description 2
- 239000006210 lotion Substances 0.000 claims description 2
- 239000002674 ointment Substances 0.000 claims description 2
- 239000000243 solution Substances 0.000 claims description 2
- 239000007921 spray Substances 0.000 claims description 2
- 238000007920 subcutaneous administration Methods 0.000 claims description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims 4
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims 4
- UTAIYTHAJQNQDW-KQYNXXCUSA-N 1-methylguanosine Chemical compound C1=NC=2C(=O)N(C)C(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O UTAIYTHAJQNQDW-KQYNXXCUSA-N 0.000 claims 2
- 241000180579 Arca Species 0.000 claims 2
- 101150077194 CAP1 gene Proteins 0.000 claims 2
- 101100245221 Mus musculus Prss8 gene Proteins 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 abstract description 70
- 239000000203 mixture Substances 0.000 abstract description 13
- 230000001225 therapeutic effect Effects 0.000 abstract description 10
- 238000002360 preparation method Methods 0.000 abstract description 5
- 108090000623 proteins and genes Proteins 0.000 description 187
- 102000004169 proteins and genes Human genes 0.000 description 162
- 235000018102 proteins Nutrition 0.000 description 156
- 102000035195 Peptidases Human genes 0.000 description 75
- 108091005804 Peptidases Proteins 0.000 description 75
- 230000000670 limiting effect Effects 0.000 description 75
- 235000019833 protease Nutrition 0.000 description 75
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 68
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 68
- 235000018417 cysteine Nutrition 0.000 description 68
- 108020003589 5' Untranslated Regions Proteins 0.000 description 60
- 235000001014 amino acid Nutrition 0.000 description 55
- 150000001413 amino acids Chemical class 0.000 description 54
- 229940024606 amino acid Drugs 0.000 description 53
- 102100033810 RAC-alpha serine/threonine-protein kinase Human genes 0.000 description 52
- 108091007780 MiR-122 Proteins 0.000 description 41
- 108091051828 miR-122 stem-loop Proteins 0.000 description 41
- 102100027831 14-3-3 protein theta Human genes 0.000 description 37
- 229920002477 rna polymer Polymers 0.000 description 37
- 230000014616 translation Effects 0.000 description 37
- 230000003612 virological effect Effects 0.000 description 37
- 230000004913 activation Effects 0.000 description 34
- 102000008109 Mixed Function Oxygenases Human genes 0.000 description 33
- 108010074633 Mixed Function Oxygenases Proteins 0.000 description 33
- 102000004271 Tryptophan 5-monooxygenases Human genes 0.000 description 33
- 108090000885 Tryptophan 5-monooxygenases Proteins 0.000 description 33
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 32
- 108091070501 miRNA Proteins 0.000 description 32
- 241001529936 Murinae Species 0.000 description 30
- 108700020796 Oncogene Proteins 0.000 description 30
- 239000012634 fragment Substances 0.000 description 28
- 230000028327 secretion Effects 0.000 description 28
- 108091008611 Protein Kinase B Proteins 0.000 description 27
- 238000006467 substitution reaction Methods 0.000 description 27
- 108010053291 Oncogene Protein v-akt Proteins 0.000 description 26
- 208000008732 thymoma Diseases 0.000 description 26
- 101150077031 DAXX gene Proteins 0.000 description 25
- 102100028559 Death domain-associated protein 6 Human genes 0.000 description 25
- 102000010170 Death domains Human genes 0.000 description 25
- 108050001718 Death domains Proteins 0.000 description 25
- -1 Nl-methyl-guanosine Chemical compound 0.000 description 25
- 102100035904 Caspase-1 Human genes 0.000 description 24
- 230000006870 function Effects 0.000 description 22
- 241000282414 Homo sapiens Species 0.000 description 21
- 108091081024 Start codon Proteins 0.000 description 20
- 238000013518 transcription Methods 0.000 description 20
- 230000035897 transcription Effects 0.000 description 19
- 102100026548 Caspase-8 Human genes 0.000 description 17
- 108010076504 Protein Sorting Signals Proteins 0.000 description 17
- 238000006243 chemical reaction Methods 0.000 description 17
- 210000003470 mitochondria Anatomy 0.000 description 17
- 230000014621 translational initiation Effects 0.000 description 17
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 15
- 125000000539 amino acid group Chemical group 0.000 description 15
- 239000000126 substance Substances 0.000 description 15
- 108090000538 Caspase-8 Proteins 0.000 description 14
- 238000007792 addition Methods 0.000 description 14
- 125000003275 alpha amino acid group Chemical group 0.000 description 14
- 230000015556 catabolic process Effects 0.000 description 14
- 239000002299 complementary DNA Substances 0.000 description 14
- 238000006731 degradation reaction Methods 0.000 description 14
- 238000000746 purification Methods 0.000 description 14
- 108020005176 AU Rich Elements Proteins 0.000 description 13
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 13
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 13
- 238000000338 in vitro Methods 0.000 description 13
- 238000003780 insertion Methods 0.000 description 13
- 230000037431 insertion Effects 0.000 description 13
- 239000003446 ligand Substances 0.000 description 13
- 108090000426 Caspase-1 Proteins 0.000 description 12
- 101000715398 Homo sapiens Caspase-1 Proteins 0.000 description 12
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 12
- 230000034994 death Effects 0.000 description 12
- 238000013461 design Methods 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 230000001105 regulatory effect Effects 0.000 description 12
- 238000011144 upstream manufacturing Methods 0.000 description 12
- 108090000397 Caspase 3 Proteins 0.000 description 11
- 102100029855 Caspase-3 Human genes 0.000 description 11
- 108091079658 miR-142-1 stem-loop Proteins 0.000 description 11
- 108091071830 miR-142-2 stem-loop Proteins 0.000 description 11
- 230000008569 process Effects 0.000 description 11
- 241000894007 species Species 0.000 description 11
- 230000004083 survival effect Effects 0.000 description 11
- 238000001890 transfection Methods 0.000 description 11
- 239000013598 vector Substances 0.000 description 11
- 108090000567 Caspase 7 Proteins 0.000 description 10
- 102100038902 Caspase-7 Human genes 0.000 description 10
- 108091007767 MALAT1 Proteins 0.000 description 10
- 102000044126 RNA-Binding Proteins Human genes 0.000 description 10
- 108700009124 Transcription Initiation Site Proteins 0.000 description 10
- 230000003213 activating effect Effects 0.000 description 10
- 230000001640 apoptogenic effect Effects 0.000 description 10
- 235000018977 lysine Nutrition 0.000 description 10
- 125000006850 spacer group Chemical group 0.000 description 10
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 9
- 108091007065 BIRCs Proteins 0.000 description 9
- 108091026890 Coding region Proteins 0.000 description 9
- 108010033040 Histones Proteins 0.000 description 9
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 9
- 102100040247 Tumor necrosis factor Human genes 0.000 description 9
- 239000000556 agonist Substances 0.000 description 9
- 238000004128 high performance liquid chromatography Methods 0.000 description 9
- 102000028499 poly(A) binding Human genes 0.000 description 9
- 108091023021 poly(A) binding Proteins 0.000 description 9
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 8
- 102000004631 Calcineurin Human genes 0.000 description 8
- 108010042955 Calcineurin Proteins 0.000 description 8
- 108020004414 DNA Proteins 0.000 description 8
- 108010044467 Isoenzymes Proteins 0.000 description 8
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 8
- 239000004472 Lysine Substances 0.000 description 8
- 229940124160 Myc inhibitor Drugs 0.000 description 8
- 238000005571 anion exchange chromatography Methods 0.000 description 8
- 230000008901 benefit Effects 0.000 description 8
- 230000001588 bifunctional effect Effects 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 210000004556 brain Anatomy 0.000 description 8
- 230000003197 catalytic effect Effects 0.000 description 8
- 230000007423 decrease Effects 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 239000013612 plasmid Substances 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 238000004007 reversed phase HPLC Methods 0.000 description 8
- 239000000523 sample Substances 0.000 description 8
- 230000008685 targeting Effects 0.000 description 8
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 8
- 102100038916 Caspase-5 Human genes 0.000 description 7
- 101710090333 Caspase-5 Proteins 0.000 description 7
- 102000004039 Caspase-9 Human genes 0.000 description 7
- 108090000566 Caspase-9 Proteins 0.000 description 7
- 101000801228 Homo sapiens Tumor necrosis factor receptor superfamily member 1A Proteins 0.000 description 7
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 7
- 102100033732 Tumor necrosis factor receptor superfamily member 1A Human genes 0.000 description 7
- 230000002209 hydrophobic effect Effects 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- 238000010348 incorporation Methods 0.000 description 7
- 230000003993 interaction Effects 0.000 description 7
- 238000005457 optimization Methods 0.000 description 7
- 230000001850 reproductive effect Effects 0.000 description 7
- 229930024421 Adenine Natural products 0.000 description 6
- 102100027308 Apoptosis regulator BAX Human genes 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- 102100024319 Intestinal-type alkaline phosphatase Human genes 0.000 description 6
- 108010077850 Nuclear Localization Signals Proteins 0.000 description 6
- 108091034117 Oligonucleotide Proteins 0.000 description 6
- 229960000643 adenine Drugs 0.000 description 6
- 229940104302 cytosine Drugs 0.000 description 6
- 239000003623 enhancer Substances 0.000 description 6
- 230000002255 enzymatic effect Effects 0.000 description 6
- 229940088598 enzyme Drugs 0.000 description 6
- 210000003494 hepatocyte Anatomy 0.000 description 6
- 210000004185 liver Anatomy 0.000 description 6
- 230000011664 signaling Effects 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- PQGCEDQWHSBAJP-TXICZTDVSA-N 5-O-phosphono-alpha-D-ribofuranosyl diphosphate Chemical compound O[C@H]1[C@@H](O)[C@@H](O[P@](O)(=O)OP(O)(O)=O)O[C@@H]1COP(O)(O)=O PQGCEDQWHSBAJP-TXICZTDVSA-N 0.000 description 5
- 101710159080 Aconitate hydratase A Proteins 0.000 description 5
- 101710159078 Aconitate hydratase B Proteins 0.000 description 5
- 108091012583 BCL2 Proteins 0.000 description 5
- 102100021662 Baculoviral IAP repeat-containing protein 3 Human genes 0.000 description 5
- 102100032857 Cyclin-dependent kinase 1 Human genes 0.000 description 5
- 102100038023 DNA fragmentation factor subunit beta Human genes 0.000 description 5
- 102100021838 E3 ubiquitin-protein ligase SIAH1 Human genes 0.000 description 5
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical group C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 5
- 101000616722 Homo sapiens E3 ubiquitin-protein ligase SIAH1 Proteins 0.000 description 5
- 101000798007 Homo sapiens RAC-gamma serine/threonine-protein kinase Proteins 0.000 description 5
- 102000003960 Ligases Human genes 0.000 description 5
- 108090000364 Ligases Proteins 0.000 description 5
- 108091093082 MiR-146 Proteins 0.000 description 5
- 102100032314 RAC-gamma serine/threonine-protein kinase Human genes 0.000 description 5
- 108700020471 RNA-Binding Proteins Proteins 0.000 description 5
- 230000004570 RNA-binding Effects 0.000 description 5
- 101710105008 RNA-binding protein Proteins 0.000 description 5
- 102000040945 Transcription factor Human genes 0.000 description 5
- 108091023040 Transcription factor Proteins 0.000 description 5
- 229960000074 biopharmaceutical Drugs 0.000 description 5
- 230000022131 cell cycle Effects 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 238000003776 cleavage reaction Methods 0.000 description 5
- 238000012217 deletion Methods 0.000 description 5
- 230000037430 deletion Effects 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 230000018109 developmental process Effects 0.000 description 5
- 210000001808 exosome Anatomy 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- 238000003752 polymerase chain reaction Methods 0.000 description 5
- 230000004481 post-translational protein modification Effects 0.000 description 5
- 230000007017 scission Effects 0.000 description 5
- 210000003491 skin Anatomy 0.000 description 5
- 230000032258 transport Effects 0.000 description 5
- 239000001226 triphosphate Substances 0.000 description 5
- 239000004475 Arginine Substances 0.000 description 4
- 101710177962 Baculoviral IAP repeat-containing protein 3 Proteins 0.000 description 4
- 102100025221 CD70 antigen Human genes 0.000 description 4
- 102000014914 Carrier Proteins Human genes 0.000 description 4
- 102000004018 Caspase 6 Human genes 0.000 description 4
- 108090000425 Caspase 6 Proteins 0.000 description 4
- 102000004068 Caspase-10 Human genes 0.000 description 4
- 108090000572 Caspase-10 Proteins 0.000 description 4
- 108010076667 Caspases Proteins 0.000 description 4
- 102000011727 Caspases Human genes 0.000 description 4
- 108090000994 Catalytic RNA Proteins 0.000 description 4
- 102000053642 Catalytic RNA Human genes 0.000 description 4
- 102100030497 Cytochrome c Human genes 0.000 description 4
- 101710103962 Cytochrome c, somatic Proteins 0.000 description 4
- 102000010831 Cytoskeletal Proteins Human genes 0.000 description 4
- 108010037414 Cytoskeletal Proteins Proteins 0.000 description 4
- 102100034235 ELAV-like protein 1 Human genes 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 102100021186 Granulysin Human genes 0.000 description 4
- 101710168479 Granulysin Proteins 0.000 description 4
- 101000934356 Homo sapiens CD70 antigen Proteins 0.000 description 4
- 101000764535 Homo sapiens Lymphotoxin-alpha Proteins 0.000 description 4
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 4
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 4
- 102100026238 Lymphotoxin-alpha Human genes 0.000 description 4
- 108091027543 MALAT1-associated small cytoplasmic RNA Proteins 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 108010052285 Membrane Proteins Proteins 0.000 description 4
- 108091092724 Noncoding DNA Proteins 0.000 description 4
- 102000007999 Nuclear Proteins Human genes 0.000 description 4
- 108010089610 Nuclear Proteins Proteins 0.000 description 4
- 102000002508 Peptide Elongation Factors Human genes 0.000 description 4
- 108010068204 Peptide Elongation Factors Proteins 0.000 description 4
- 101710137500 T7 RNA polymerase Proteins 0.000 description 4
- 241000700605 Viruses Species 0.000 description 4
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 4
- 108091008324 binding proteins Proteins 0.000 description 4
- 238000004422 calculation algorithm Methods 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 238000010276 construction Methods 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- 230000001086 cytosolic effect Effects 0.000 description 4
- 210000002889 endothelial cell Anatomy 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 230000002779 inactivation Effects 0.000 description 4
- 210000004020 intracellular membrane Anatomy 0.000 description 4
- 208000032839 leukemia Diseases 0.000 description 4
- 230000004807 localization Effects 0.000 description 4
- 230000003278 mimic effect Effects 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- PTJWIQPHWPFNBW-GBNDHIKLSA-N pseudouridine Chemical class O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1C1=CNC(=O)NC1=O PTJWIQPHWPFNBW-GBNDHIKLSA-N 0.000 description 4
- 230000003362 replicative effect Effects 0.000 description 4
- 108091092562 ribozyme Proteins 0.000 description 4
- 239000004055 small Interfering RNA Substances 0.000 description 4
- 230000000153 supplemental effect Effects 0.000 description 4
- 229940113082 thymine Drugs 0.000 description 4
- 238000012384 transportation and delivery Methods 0.000 description 4
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 3
- 108010008014 B-Cell Maturation Antigen Proteins 0.000 description 3
- 102000006942 B-Cell Maturation Antigen Human genes 0.000 description 3
- 102100032616 Caspase-2 Human genes 0.000 description 3
- 108090000552 Caspase-2 Proteins 0.000 description 3
- 102100025597 Caspase-4 Human genes 0.000 description 3
- 101710090338 Caspase-4 Proteins 0.000 description 3
- 102000008186 Collagen Human genes 0.000 description 3
- 108010035532 Collagen Proteins 0.000 description 3
- 102100026865 Cyclin-dependent kinase 5 activator 1 Human genes 0.000 description 3
- 102100037362 Fibronectin Human genes 0.000 description 3
- 108010067306 Fibronectins Proteins 0.000 description 3
- 241000710198 Foot-and-mouth disease virus Species 0.000 description 3
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 3
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 description 3
- 101000983528 Homo sapiens Caspase-8 Proteins 0.000 description 3
- 101000597785 Homo sapiens Tumor necrosis factor receptor superfamily member 6B Proteins 0.000 description 3
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 description 3
- 206010021143 Hypoxia Diseases 0.000 description 3
- 102000055031 Inhibitor of Apoptosis Proteins Human genes 0.000 description 3
- 108091092195 Intron Proteins 0.000 description 3
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 3
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 3
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 3
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 3
- 108060001084 Luciferase Proteins 0.000 description 3
- 239000005089 Luciferase Substances 0.000 description 3
- 102000001291 MAP Kinase Kinase Kinase Human genes 0.000 description 3
- 108060006687 MAP kinase kinase kinase Proteins 0.000 description 3
- 108010066154 Nuclear Export Signals Proteins 0.000 description 3
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 3
- 102000028391 RNA cap binding Human genes 0.000 description 3
- 108091000106 RNA cap binding Proteins 0.000 description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 3
- 108020004459 Small interfering RNA Proteins 0.000 description 3
- 108091036066 Three prime untranslated region Proteins 0.000 description 3
- 239000004473 Threonine Substances 0.000 description 3
- 108020004566 Transfer RNA Proteins 0.000 description 3
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 3
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 3
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 235000004279 alanine Nutrition 0.000 description 3
- 230000003321 amplification Effects 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000033115 angiogenesis Effects 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 230000033228 biological regulation Effects 0.000 description 3
- 150000001720 carbohydrates Chemical class 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 229920001436 collagen Polymers 0.000 description 3
- 230000021615 conjugation Effects 0.000 description 3
- 239000002537 cosmetic Substances 0.000 description 3
- 230000003828 downregulation Effects 0.000 description 3
- 235000013922 glutamic acid Nutrition 0.000 description 3
- 229960002989 glutamic acid Drugs 0.000 description 3
- 239000004220 glutamic acid Substances 0.000 description 3
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 3
- 235000004554 glutamine Nutrition 0.000 description 3
- 230000028993 immune response Effects 0.000 description 3
- 229960000310 isoleucine Drugs 0.000 description 3
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 230000002503 metabolic effect Effects 0.000 description 3
- 238000007069 methylation reaction Methods 0.000 description 3
- 239000003226 mitogen Substances 0.000 description 3
- 238000003199 nucleic acid amplification method Methods 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 230000009758 senescence Effects 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 238000013517 stratification Methods 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 238000011191 terminal modification Methods 0.000 description 3
- 230000001960 triggered effect Effects 0.000 description 3
- 235000011178 triphosphate Nutrition 0.000 description 3
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 3
- 229960005486 vaccine Drugs 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- QOXJRLADYHZRGC-SHYZEUOFSA-N 1-[(2r,3r,5s)-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione Chemical compound O1[C@H](CO)C[C@@H](O)[C@@H]1N1C(=O)NC(=O)C=C1 QOXJRLADYHZRGC-SHYZEUOFSA-N 0.000 description 2
- WVXRAFOPTSTNLL-NKWVEPMBSA-N 2',3'-dideoxyadenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1CC[C@@H](CO)O1 WVXRAFOPTSTNLL-NKWVEPMBSA-N 0.000 description 2
- BTOTXLJHDSNXMW-POYBYMJQSA-N 2,3-dideoxyuridine Chemical compound O1[C@H](CO)CC[C@@H]1N1C(=O)NC(=O)C=C1 BTOTXLJHDSNXMW-POYBYMJQSA-N 0.000 description 2
- OFEZSBMBBKLLBJ-UHFFFAOYSA-N 2-(6-aminopurin-9-yl)-5-(hydroxymethyl)oxolan-3-ol Chemical compound C1=NC=2C(N)=NC=NC=2N1C1OC(CO)CC1O OFEZSBMBBKLLBJ-UHFFFAOYSA-N 0.000 description 2
- OCLZPNCLRLDXJC-NTSWFWBYSA-N 2-amino-9-[(2r,5s)-5-(hydroxymethyl)oxolan-2-yl]-3h-purin-6-one Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@H]1CC[C@@H](CO)O1 OCLZPNCLRLDXJC-NTSWFWBYSA-N 0.000 description 2
- OROIAVZITJBGSM-OBXARNEKSA-N 3'-deoxyguanosine Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](CO)C[C@H]1O OROIAVZITJBGSM-OBXARNEKSA-N 0.000 description 2
- 101710103970 ADP,ATP carrier protein Proteins 0.000 description 2
- 101710133192 ADP,ATP carrier protein, mitochondrial Proteins 0.000 description 2
- 102000011690 Adiponectin Human genes 0.000 description 2
- 108010076365 Adiponectin Proteins 0.000 description 2
- 108091023037 Aptamer Proteins 0.000 description 2
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
- 241000193830 Bacillus <bacterium> Species 0.000 description 2
- 102100021334 Bcl-2-related protein A1 Human genes 0.000 description 2
- 108010045374 CD36 Antigens Proteins 0.000 description 2
- 102000053028 CD36 Antigens Human genes 0.000 description 2
- 108010029697 CD40 Ligand Proteins 0.000 description 2
- 102100032937 CD40 ligand Human genes 0.000 description 2
- 208000005623 Carcinogenesis Diseases 0.000 description 2
- 241000710777 Classical swine fever virus Species 0.000 description 2
- 241000710127 Cricket paralysis virus Species 0.000 description 2
- MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 2
- 108010025454 Cyclin-Dependent Kinase 5 Proteins 0.000 description 2
- 102100026805 Cyclin-dependent-like kinase 5 Human genes 0.000 description 2
- 108010052832 Cytochromes Proteins 0.000 description 2
- 102000018832 Cytochromes Human genes 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 2
- 102000053602 DNA Human genes 0.000 description 2
- 230000005971 DNA damage repair Effects 0.000 description 2
- 101710147299 DNA fragmentation factor subunit beta Proteins 0.000 description 2
- 108010008532 Deoxyribonuclease I Proteins 0.000 description 2
- 102000007260 Deoxyribonuclease I Human genes 0.000 description 2
- 108010016626 Dipeptides Proteins 0.000 description 2
- 238000008157 ELISA kit Methods 0.000 description 2
- 241000710188 Encephalomyocarditis virus Species 0.000 description 2
- 108010042407 Endonucleases Proteins 0.000 description 2
- 102000004533 Endonucleases Human genes 0.000 description 2
- 241000991587 Enterovirus C Species 0.000 description 2
- 102100022462 Eukaryotic initiation factor 4A-II Human genes 0.000 description 2
- 102000004547 Glucosylceramidase Human genes 0.000 description 2
- 108010017544 Glucosylceramidase Proteins 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 102000003886 Glycoproteins Human genes 0.000 description 2
- 108090000288 Glycoproteins Proteins 0.000 description 2
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 2
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 2
- 108091027874 Group I catalytic intron Proteins 0.000 description 2
- 241000711557 Hepacivirus Species 0.000 description 2
- 101000894929 Homo sapiens Bcl-2-related protein A1 Proteins 0.000 description 2
- 101000950965 Homo sapiens DNA fragmentation factor subunit beta Proteins 0.000 description 2
- 101001044475 Homo sapiens Eukaryotic initiation factor 4A-II Proteins 0.000 description 2
- 101001008919 Homo sapiens Kallikrein-10 Proteins 0.000 description 2
- 101001050288 Homo sapiens Transcription factor Jun Proteins 0.000 description 2
- 101000611185 Homo sapiens Tumor necrosis factor receptor superfamily member 5 Proteins 0.000 description 2
- 102100027613 Kallikrein-10 Human genes 0.000 description 2
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- 108091064450 Ligase ribozyme Proteins 0.000 description 2
- 108091062170 Mir-22 Proteins 0.000 description 2
- 108091028049 Mir-221 microRNA Proteins 0.000 description 2
- 241000714177 Murine leukemia virus Species 0.000 description 2
- 102100032970 Myogenin Human genes 0.000 description 2
- 108010056785 Myogenin Proteins 0.000 description 2
- 102100030856 Myoglobin Human genes 0.000 description 2
- 108010062374 Myoglobin Proteins 0.000 description 2
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
- 102000004316 Oxidoreductases Human genes 0.000 description 2
- 108090000854 Oxidoreductases Proteins 0.000 description 2
- 108091093037 Peptide nucleic acid Proteins 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- 241000709664 Picornaviridae Species 0.000 description 2
- 108091007412 Piwi-interacting RNA Proteins 0.000 description 2
- 101710086015 RNA ligase Proteins 0.000 description 2
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 2
- 238000012300 Sequence Analysis Methods 0.000 description 2
- 108020003224 Small Nucleolar RNA Proteins 0.000 description 2
- 102000042773 Small Nucleolar RNA Human genes 0.000 description 2
- 108700026226 TATA Box Proteins 0.000 description 2
- 108091046869 Telomeric non-coding RNA Proteins 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 101001023030 Toxoplasma gondii Myosin-D Proteins 0.000 description 2
- 102100023132 Transcription factor Jun Human genes 0.000 description 2
- 206010046865 Vaccinia virus infection Diseases 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 238000001261 affinity purification Methods 0.000 description 2
- 125000000304 alkynyl group Chemical group 0.000 description 2
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 2
- 230000001028 anti-proliverative effect Effects 0.000 description 2
- 230000000692 anti-sense effect Effects 0.000 description 2
- 230000030741 antigen processing and presentation Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 235000009582 asparagine Nutrition 0.000 description 2
- 229960001230 asparagine Drugs 0.000 description 2
- 229960005261 aspartic acid Drugs 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
- 210000001124 body fluid Anatomy 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 230000036952 cancer formation Effects 0.000 description 2
- 238000005251 capillar electrophoresis Methods 0.000 description 2
- 238000001818 capillary gel electrophoresis Methods 0.000 description 2
- 231100000504 carcinogenesis Toxicity 0.000 description 2
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 2
- 238000004590 computer program Methods 0.000 description 2
- 239000000356 contaminant Substances 0.000 description 2
- CVSVTCORWBXHQV-UHFFFAOYSA-N creatine Chemical compound NC(=[NH2+])N(C)CC([O-])=O CVSVTCORWBXHQV-UHFFFAOYSA-N 0.000 description 2
- 230000001120 cytoprotective effect Effects 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 238000000432 density-gradient centrifugation Methods 0.000 description 2
- 230000001627 detrimental effect Effects 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 238000001085 differential centrifugation Methods 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 210000003608 fece Anatomy 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- 238000013467 fragmentation Methods 0.000 description 2
- 238000006062 fragmentation reaction Methods 0.000 description 2
- 238000007306 functionalization reaction Methods 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 108091008039 hormone receptors Proteins 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 230000007954 hypoxia Effects 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 230000000415 inactivating effect Effects 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 150000002669 lysines Chemical class 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 230000011987 methylation Effects 0.000 description 2
- 108091061917 miR-221 stem-loop Proteins 0.000 description 2
- 108091063489 miR-221-1 stem-loop Proteins 0.000 description 2
- 108091055391 miR-221-2 stem-loop Proteins 0.000 description 2
- 108091031076 miR-221-3 stem-loop Proteins 0.000 description 2
- 230000002438 mitochondrial effect Effects 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 210000000066 myeloid cell Anatomy 0.000 description 2
- 238000002515 oligonucleotide synthesis Methods 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 102000020233 phosphotransferase Human genes 0.000 description 2
- 230000008488 polyadenylation Effects 0.000 description 2
- 210000004909 pre-ejaculatory fluid Anatomy 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 210000002307 prostate Anatomy 0.000 description 2
- 108020001580 protein domains Proteins 0.000 description 2
- ZCCUUQDIBDJBTK-UHFFFAOYSA-N psoralen Chemical compound C1=C2OC(=O)C=CC2=CC2=C1OC=C2 ZCCUUQDIBDJBTK-UHFFFAOYSA-N 0.000 description 2
- 238000000275 quality assurance Methods 0.000 description 2
- 238000003908 quality control method Methods 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000001542 size-exclusion chromatography Methods 0.000 description 2
- 238000005287 template synthesis Methods 0.000 description 2
- 230000002123 temporal effect Effects 0.000 description 2
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 2
- 230000002103 transcriptional effect Effects 0.000 description 2
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 2
- 230000007306 turnover Effects 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 238000000108 ultra-filtration Methods 0.000 description 2
- 208000007089 vaccinia Diseases 0.000 description 2
- 239000004474 valine Substances 0.000 description 2
- 230000008673 vomiting Effects 0.000 description 2
- FDKWRPBBCBCIGA-REOHCLBHSA-N (2r)-2-azaniumyl-3-$l^{1}-selanylpropanoate Chemical compound [Se]C[C@H](N)C(O)=O FDKWRPBBCBCIGA-REOHCLBHSA-N 0.000 description 1
- RPOKRGMOEWYIKB-ZFCLCKFASA-N (2r,3r,4r,5r)-n-[(4-ethenylphenyl)methyl]-2,3,6-trihydroxy-5-methyl-4-[(2r,3r,4s,5r,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyhexanamide Chemical compound O([C@H]([C@@H](CO)C)[C@H](O)[C@@H](O)C(=O)NCC=1C=CC(C=C)=CC=1)[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O RPOKRGMOEWYIKB-ZFCLCKFASA-N 0.000 description 1
- ZIZMDHZLHJBNSQ-UHFFFAOYSA-N 1,2-dihydrophenazine Chemical compound C1=CC=C2N=C(C=CCC3)C3=NC2=C1 ZIZMDHZLHJBNSQ-UHFFFAOYSA-N 0.000 description 1
- 125000003287 1H-imidazol-4-ylmethyl group Chemical group [H]N1C([H])=NC(C([H])([H])[*])=C1[H] 0.000 description 1
- VEPOHXYIFQMVHW-XOZOLZJESA-N 2,3-dihydroxybutanedioic acid (2S,3S)-3,4-dimethyl-2-phenylmorpholine Chemical compound OC(C(O)C(O)=O)C(O)=O.C[C@H]1[C@@H](OCCN1C)c1ccccc1 VEPOHXYIFQMVHW-XOZOLZJESA-N 0.000 description 1
- BVLGKOVALHRKNM-XUTVFYLZSA-N 2-Thio-1-methylpseudouridine Chemical compound CN1C=C(C(=O)NC1=S)[C@H]2[C@@H]([C@@H]([C@H](O2)CO)O)O BVLGKOVALHRKNM-XUTVFYLZSA-N 0.000 description 1
- CWXIOHYALLRNSZ-JWMKEVCDSA-N 2-Thiodihydropseudouridine Chemical compound C1C(C(=O)NC(=S)N1)[C@H]2[C@@H]([C@@H]([C@H](O2)CO)O)O CWXIOHYALLRNSZ-JWMKEVCDSA-N 0.000 description 1
- LRFJOIPOPUJUMI-KWXKLSQISA-N 2-[2,2-bis[(9z,12z)-octadeca-9,12-dienyl]-1,3-dioxolan-4-yl]-n,n-dimethylethanamine Chemical compound CCCCC\C=C/C\C=C/CCCCCCCCC1(CCCCCCCC\C=C/C\C=C/CCCCC)OCC(CCN(C)C)O1 LRFJOIPOPUJUMI-KWXKLSQISA-N 0.000 description 1
- NUBJGTNGKODGGX-YYNOVJQHSA-N 2-[5-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-2,4-dioxopyrimidin-1-yl]acetic acid Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1C1=CN(CC(O)=O)C(=O)NC1=O NUBJGTNGKODGGX-YYNOVJQHSA-N 0.000 description 1
- LCKIHCRZXREOJU-KYXWUPHJSA-N 2-[[5-[(2S,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-2,4-dioxopyrimidin-1-yl]methylamino]ethanesulfonic acid Chemical compound C(NCCS(=O)(=O)O)N1C=C([C@H]2[C@H](O)[C@H](O)[C@@H](CO)O2)C(NC1=O)=O LCKIHCRZXREOJU-KYXWUPHJSA-N 0.000 description 1
- FDKWRPBBCBCIGA-UHFFFAOYSA-N 2-azaniumyl-3-$l^{1}-selanylpropanoate Chemical compound [Se]CC(N)C(O)=O FDKWRPBBCBCIGA-UHFFFAOYSA-N 0.000 description 1
- RLZMYTZDQAVNIN-ZOQUXTDFSA-N 2-methoxy-4-thio-uridine Chemical compound COC1=NC(=S)C=CN1[C@H]2[C@@H]([C@@H]([C@H](O2)CO)O)O RLZMYTZDQAVNIN-ZOQUXTDFSA-N 0.000 description 1
- WBVPJIKOWUQTSD-ZOQUXTDFSA-N 2-methoxyuridine Chemical compound COC1=NC(=O)C=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 WBVPJIKOWUQTSD-ZOQUXTDFSA-N 0.000 description 1
- KPGXRSRHYNQIFN-UHFFFAOYSA-N 2-oxoglutaric acid Chemical compound OC(=O)CCC(=O)C(O)=O KPGXRSRHYNQIFN-UHFFFAOYSA-N 0.000 description 1
- 108020005065 3' Flanking Region Proteins 0.000 description 1
- DXEJZRDJXRVUPN-XUTVFYLZSA-N 3-Methylpseudouridine Chemical compound O=C1N(C)C(=O)NC=C1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 DXEJZRDJXRVUPN-XUTVFYLZSA-N 0.000 description 1
- FGFVODMBKZRMMW-XUTVFYLZSA-N 4-Methoxy-2-thiopseudouridine Chemical compound COC1=C(C=NC(=S)N1)[C@H]2[C@@H]([C@@H]([C@H](O2)CO)O)O FGFVODMBKZRMMW-XUTVFYLZSA-N 0.000 description 1
- HOCJTJWYMOSXMU-XUTVFYLZSA-N 4-Methoxypseudouridine Chemical compound COC1=C(C=NC(=O)N1)[C@H]2[C@@H]([C@@H]([C@H](O2)CO)O)O HOCJTJWYMOSXMU-XUTVFYLZSA-N 0.000 description 1
- VTGBLFNEDHVUQA-XUTVFYLZSA-N 4-Thio-1-methyl-pseudouridine Chemical compound S=C1NC(=O)N(C)C=C1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 VTGBLFNEDHVUQA-XUTVFYLZSA-N 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- 108020005029 5' Flanking Region Proteins 0.000 description 1
- ITGWEVGJUSMCEA-KYXWUPHJSA-N 5-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1-prop-1-ynylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)N(C#CC)C=C1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 ITGWEVGJUSMCEA-KYXWUPHJSA-N 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
- 208000010444 Acidosis Diseases 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- 239000004382 Amylase Substances 0.000 description 1
- 102000013142 Amylases Human genes 0.000 description 1
- 108010065511 Amylases Proteins 0.000 description 1
- 108010085443 Anserine Proteins 0.000 description 1
- 108020005544 Antisense RNA Proteins 0.000 description 1
- 101710081722 Antitrypsin Proteins 0.000 description 1
- 102000007592 Apolipoproteins Human genes 0.000 description 1
- 108010071619 Apolipoproteins Proteins 0.000 description 1
- 108010033604 Apoptosis Inducing Factor Proteins 0.000 description 1
- 102000007272 Apoptosis Inducing Factor Human genes 0.000 description 1
- 101000719121 Arabidopsis thaliana Protein MEI2-like 1 Proteins 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 108700028946 BCL2-like 10 Proteins 0.000 description 1
- 108700003785 Baculoviral IAP Repeat-Containing 3 Proteins 0.000 description 1
- 241000709756 Barley yellow dwarf virus Species 0.000 description 1
- 241000709750 Barley yellow dwarf virus-PAV Species 0.000 description 1
- 102100021971 Bcl-2-interacting killer Human genes 0.000 description 1
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
- 102100034476 CCA tRNA nucleotidyltransferase 1, mitochondrial Human genes 0.000 description 1
- 101710186200 CCAAT/enhancer-binding protein Proteins 0.000 description 1
- 102100027207 CD27 antigen Human genes 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 102100029968 Calreticulin Human genes 0.000 description 1
- 108090000549 Calreticulin Proteins 0.000 description 1
- QRYRORQUOLYVBU-VBKZILBWSA-N Carnosic acid Natural products CC([C@@H]1CC2)(C)CCC[C@]1(C(O)=O)C1=C2C=C(C(C)C)C(O)=C1O QRYRORQUOLYVBU-VBKZILBWSA-N 0.000 description 1
- 108010087806 Carnosine Proteins 0.000 description 1
- 102000005600 Cathepsins Human genes 0.000 description 1
- 108010084457 Cathepsins Proteins 0.000 description 1
- 101150058477 Cdk5r1 gene Proteins 0.000 description 1
- 208000027104 Chemotherapy-Related Cognitive Impairment Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 102100034229 Citramalyl-CoA lyase, mitochondrial Human genes 0.000 description 1
- 102100022641 Coagulation factor IX Human genes 0.000 description 1
- 102000002734 Collagen Type VI Human genes 0.000 description 1
- 108010043741 Collagen Type VI Proteins 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 239000004971 Cross linker Substances 0.000 description 1
- FDKWRPBBCBCIGA-UWTATZPHSA-N D-Selenocysteine Natural products [Se]C[C@@H](N)C(O)=O FDKWRPBBCBCIGA-UWTATZPHSA-N 0.000 description 1
- 230000005778 DNA damage Effects 0.000 description 1
- 231100000277 DNA damage Toxicity 0.000 description 1
- 108010008286 DNA nucleotidylexotransferase Proteins 0.000 description 1
- 230000033616 DNA repair Effects 0.000 description 1
- 102100029764 DNA-directed DNA/RNA polymerase mu Human genes 0.000 description 1
- 101100481404 Danio rerio tie1 gene Proteins 0.000 description 1
- 102220577240 Density-regulated protein_K93Y_mutation Human genes 0.000 description 1
- 108091027757 Deoxyribozyme Proteins 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- YKWUPFSEFXSGRT-JWMKEVCDSA-N Dihydropseudouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1C1C(=O)NC(=O)NC1 YKWUPFSEFXSGRT-JWMKEVCDSA-N 0.000 description 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- 101100361074 Drosophila melanogaster RNaseZ gene Proteins 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
- 108010053101 ELAV Proteins Proteins 0.000 description 1
- 102000016662 ELAV Proteins Human genes 0.000 description 1
- 102000003951 Erythropoietin Human genes 0.000 description 1
- 108090000394 Erythropoietin Proteins 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 101710091918 Eukaryotic translation initiation factor 4E Proteins 0.000 description 1
- 102100027304 Eukaryotic translation initiation factor 4E Human genes 0.000 description 1
- 101710126428 Eukaryotic translation initiation factor 4E-2 Proteins 0.000 description 1
- 101710126416 Eukaryotic translation initiation factor 4E-3 Proteins 0.000 description 1
- 101710126432 Eukaryotic translation initiation factor 4E1 Proteins 0.000 description 1
- 101710133325 Eukaryotic translation initiation factor NCBP Proteins 0.000 description 1
- 101710190212 Eukaryotic translation initiation factor isoform 4E Proteins 0.000 description 1
- 101710124729 Eukaryotic translation initiation factor isoform 4E-2 Proteins 0.000 description 1
- 108010076282 Factor IX Proteins 0.000 description 1
- 102000001690 Factor VIII Human genes 0.000 description 1
- 108010054218 Factor VIII Proteins 0.000 description 1
- 101100289797 Fusarium sp LUC1 gene Proteins 0.000 description 1
- 101100289798 Fusarium sp LUC2 gene Proteins 0.000 description 1
- 101100289799 Fusarium sp LUC3 gene Proteins 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 102100040004 Gamma-glutamylcyclotransferase Human genes 0.000 description 1
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
- 102100039619 Granulocyte colony-stimulating factor Human genes 0.000 description 1
- 102000002812 Heat-Shock Proteins Human genes 0.000 description 1
- 108010004889 Heat-Shock Proteins Proteins 0.000 description 1
- 102100021519 Hemoglobin subunit beta Human genes 0.000 description 1
- 108091005904 Hemoglobin subunit beta Proteins 0.000 description 1
- 241000724709 Hepatitis delta virus Species 0.000 description 1
- JNPRQUIWDVDHIT-GYIPPJPDSA-N Herculin Chemical compound CCC\C=C\CCCC\C=C\C(=O)NCC(C)C JNPRQUIWDVDHIT-GYIPPJPDSA-N 0.000 description 1
- JNPRQUIWDVDHIT-UHFFFAOYSA-N Herculin Natural products CCCC=CCCCCC=CC(=O)NCC(C)C JNPRQUIWDVDHIT-UHFFFAOYSA-N 0.000 description 1
- 102000006479 Heterogeneous-Nuclear Ribonucleoproteins Human genes 0.000 description 1
- 108010019372 Heterogeneous-Nuclear Ribonucleoproteins Proteins 0.000 description 1
- 102000003964 Histone deacetylase Human genes 0.000 description 1
- 108090000353 Histone deacetylase Proteins 0.000 description 1
- 102000009331 Homeodomain Proteins Human genes 0.000 description 1
- 108010048671 Homeodomain Proteins Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000970576 Homo sapiens Bcl-2-interacting killer Proteins 0.000 description 1
- 101000914511 Homo sapiens CD27 antigen Proteins 0.000 description 1
- 101000886680 Homo sapiens Gamma-glutamylcyclotransferase Proteins 0.000 description 1
- 101001078143 Homo sapiens Integrin alpha-IIb Proteins 0.000 description 1
- 101001046686 Homo sapiens Integrin alpha-M Proteins 0.000 description 1
- 101000935040 Homo sapiens Integrin beta-2 Proteins 0.000 description 1
- 101000896414 Homo sapiens Nuclear nucleic acid-binding protein C1D Proteins 0.000 description 1
- 101001043564 Homo sapiens Prolow-density lipoprotein receptor-related protein 1 Proteins 0.000 description 1
- 101001120822 Homo sapiens Putative microRNA 17 host gene protein Proteins 0.000 description 1
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 1
- 101000857677 Homo sapiens Runt-related transcription factor 1 Proteins 0.000 description 1
- 101000808011 Homo sapiens Vascular endothelial growth factor A Proteins 0.000 description 1
- 101000650134 Homo sapiens WAS/WASL-interacting protein family member 2 Proteins 0.000 description 1
- 102100022875 Hypoxia-inducible factor 1-alpha Human genes 0.000 description 1
- 108050009527 Hypoxia-inducible factor-1 alpha Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102100025306 Integrin alpha-IIb Human genes 0.000 description 1
- 102100022338 Integrin alpha-M Human genes 0.000 description 1
- 102100025390 Integrin beta-2 Human genes 0.000 description 1
- 108020003285 Isocitrate lyase Proteins 0.000 description 1
- SLRNWACWRVGMKD-UHFFFAOYSA-N L-anserine Natural products CN1C=NC(CC(NC(=O)CCN)C(O)=O)=C1 SLRNWACWRVGMKD-UHFFFAOYSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- 108020005198 Long Noncoding RNA Proteins 0.000 description 1
- 108091007460 Long intergenic noncoding RNA Proteins 0.000 description 1
- 206010025282 Lymphoedema Diseases 0.000 description 1
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 description 1
- 108020004687 Malate Synthase Proteins 0.000 description 1
- 108091028066 Mir-126 Proteins 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 101100481406 Mus musculus Tie1 gene Proteins 0.000 description 1
- 102100038379 Myogenic factor 6 Human genes 0.000 description 1
- 102000003505 Myosin Human genes 0.000 description 1
- 108060008487 Myosin Proteins 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- CQOVPNPJLQNMDC-UHFFFAOYSA-N N-beta-alanyl-L-histidine Natural products NCCC(=O)NC(C(O)=O)CC1=CN=CN1 CQOVPNPJLQNMDC-UHFFFAOYSA-N 0.000 description 1
- 125000000729 N-terminal amino-acid group Chemical group 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 241000221960 Neurospora Species 0.000 description 1
- 108020004485 Nonsense Codon Proteins 0.000 description 1
- 102100021713 Nuclear nucleic acid-binding protein C1D Human genes 0.000 description 1
- 108010079246 OMPA outer membrane proteins Proteins 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- 238000009004 PCR Kit Methods 0.000 description 1
- 101150086469 PLOD1 gene Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000005228 Pericardial Effusion Diseases 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- 102000012338 Poly(ADP-ribose) Polymerases Human genes 0.000 description 1
- 108010061844 Poly(ADP-ribose) Polymerases Proteins 0.000 description 1
- 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 description 1
- 102000015623 Polynucleotide Adenylyltransferase Human genes 0.000 description 1
- 108010024055 Polynucleotide adenylyltransferase Proteins 0.000 description 1
- 241000210053 Potentilla elegans Species 0.000 description 1
- 206010036790 Productive cough Diseases 0.000 description 1
- 102000003946 Prolactin Human genes 0.000 description 1
- 108010057464 Prolactin Proteins 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 229930185560 Pseudouridine Natural products 0.000 description 1
- PTJWIQPHWPFNBW-UHFFFAOYSA-N Pseudouridine C Natural products OC1C(O)C(CO)OC1C1=CNC(=O)NC1=O PTJWIQPHWPFNBW-UHFFFAOYSA-N 0.000 description 1
- 102000007615 Pulmonary Surfactant-Associated Protein A Human genes 0.000 description 1
- 108010007100 Pulmonary Surfactant-Associated Protein A Proteins 0.000 description 1
- KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 1
- 102100026055 Putative microRNA 17 host gene protein Human genes 0.000 description 1
- 101150040459 RAS gene Proteins 0.000 description 1
- 101150076031 RAS1 gene Proteins 0.000 description 1
- 102000015097 RNA Splicing Factors Human genes 0.000 description 1
- 108010039259 RNA Splicing Factors Proteins 0.000 description 1
- 108091030071 RNAI Proteins 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 1
- 108010083644 Ribonucleases Proteins 0.000 description 1
- 102000006382 Ribonucleases Human genes 0.000 description 1
- 102000004389 Ribonucleoproteins Human genes 0.000 description 1
- 108010081734 Ribonucleoproteins Proteins 0.000 description 1
- 102000002278 Ribosomal Proteins Human genes 0.000 description 1
- 108010000605 Ribosomal Proteins Proteins 0.000 description 1
- 102100038043 Roquin-1 Human genes 0.000 description 1
- 101710168637 Roquin-1 Proteins 0.000 description 1
- 102100025373 Runt-related transcription factor 1 Human genes 0.000 description 1
- 108091006207 SLC-Transporter Proteins 0.000 description 1
- 102000037054 SLC-Transporter Human genes 0.000 description 1
- 108091006296 SLC2A1 Proteins 0.000 description 1
- 108091006300 SLC2A4 Proteins 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 240000005499 Sasa Species 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 102000054727 Serum Amyloid A Human genes 0.000 description 1
- 108700028909 Serum Amyloid A Proteins 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- 108091027967 Small hairpin RNA Proteins 0.000 description 1
- 102100023536 Solute carrier family 2, facilitated glucose transporter member 1 Human genes 0.000 description 1
- 102100033939 Solute carrier family 2, facilitated glucose transporter member 4 Human genes 0.000 description 1
- 108010017842 Telomerase Proteins 0.000 description 1
- 108020005038 Terminator Codon Proteins 0.000 description 1
- 102000004338 Transferrin Human genes 0.000 description 1
- 108090000901 Transferrin Proteins 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 102000001742 Tumor Suppressor Proteins Human genes 0.000 description 1
- 108010040002 Tumor Suppressor Proteins Proteins 0.000 description 1
- 102100039037 Vascular endothelial growth factor A Human genes 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 102100027540 WAS/WASL-interacting protein family member 2 Human genes 0.000 description 1
- 241000607479 Yersinia pestis Species 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000016383 Zea mays subsp huehuetenangensis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 230000007950 acidosis Effects 0.000 description 1
- 208000026545 acidosis disease Diseases 0.000 description 1
- 230000000758 acidotic effect Effects 0.000 description 1
- 150000001251 acridines Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 150000003838 adenosines Chemical class 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 108010026331 alpha-Fetoproteins Proteins 0.000 description 1
- 102000013529 alpha-Fetoproteins Human genes 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 210000004381 amniotic fluid Anatomy 0.000 description 1
- 235000019418 amylase Nutrition 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- MYYIAHXIVFADCU-QMMMGPOBSA-N anserine Chemical compound CN1C=NC=C1C[C@H](NC(=O)CC[NH3+])C([O-])=O MYYIAHXIVFADCU-QMMMGPOBSA-N 0.000 description 1
- 230000001475 anti-trypsic effect Effects 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 230000005756 apoptotic signaling Effects 0.000 description 1
- 210000001742 aqueous humor Anatomy 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 210000004507 artificial chromosome Anatomy 0.000 description 1
- 210000003567 ascitic fluid Anatomy 0.000 description 1
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 108010028263 bacteriophage T3 RNA polymerase Proteins 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- WGDUUQDYDIIBKT-UHFFFAOYSA-N beta-Pseudouridine Natural products OC1OC(CN2C=CC(=O)NC2=O)C(O)C1O WGDUUQDYDIIBKT-UHFFFAOYSA-N 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 230000006287 biotinylation Effects 0.000 description 1
- 238000007413 biotinylation Methods 0.000 description 1
- 210000004952 blastocoel Anatomy 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 210000002449 bone cell Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 102220366036 c.196G>T Human genes 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 239000012830 cancer therapeutic Substances 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 231100000357 carcinogen Toxicity 0.000 description 1
- 239000003183 carcinogenic agent Substances 0.000 description 1
- 229940044199 carnosine Drugs 0.000 description 1
- CQOVPNPJLQNMDC-ZETCQYMHSA-N carnosine Chemical compound [NH3+]CCC(=O)N[C@H](C([O-])=O)CC1=CNC=N1 CQOVPNPJLQNMDC-ZETCQYMHSA-N 0.000 description 1
- 108010042238 caspase-activated deoxyribonuclease Proteins 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000009087 cell motility Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 210000002939 cerumen Anatomy 0.000 description 1
- 210000003756 cervix mucus Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 210000001726 chromosome structure Anatomy 0.000 description 1
- 210000001268 chyle Anatomy 0.000 description 1
- 210000004913 chyme Anatomy 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 229960003624 creatine Drugs 0.000 description 1
- 239000006046 creatine Substances 0.000 description 1
- 210000002726 cyst fluid Anatomy 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 238000004163 cytometry Methods 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000009849 deactivation Effects 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000036267 drug metabolism Effects 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000001516 effect on protein Effects 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007705 epithelial mesenchymal transition Effects 0.000 description 1
- 229940105423 erythropoietin Drugs 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 230000017188 evasion or tolerance of host immune response Effects 0.000 description 1
- 210000003722 extracellular fluid Anatomy 0.000 description 1
- 229960004222 factor ix Drugs 0.000 description 1
- 229960000301 factor viii Drugs 0.000 description 1
- 230000004129 fatty acid metabolism Effects 0.000 description 1
- 231100000502 fertility decrease Toxicity 0.000 description 1
- 210000004700 fetal blood Anatomy 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 230000009368 gene silencing by RNA Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 229940049906 glutamate Drugs 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 1
- 125000001939 glutaminyl group Chemical group 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical compound OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 description 1
- 230000036433 growing body Effects 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- RQFCJASXJCIDSX-UUOKFMHZSA-N guanosine 5'-monophosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O RQFCJASXJCIDSX-UUOKFMHZSA-N 0.000 description 1
- 210000004209 hair Anatomy 0.000 description 1
- 208000024963 hair loss Diseases 0.000 description 1
- 230000003676 hair loss Effects 0.000 description 1
- 108090001052 hairpin ribozyme Proteins 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 210000000777 hematopoietic system Anatomy 0.000 description 1
- 235000020256 human milk Nutrition 0.000 description 1
- 210000004251 human milk Anatomy 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000012151 immunohistochemical method Methods 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 208000000509 infertility Diseases 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 231100000535 infertility Toxicity 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 239000000138 intercalating agent Substances 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 108700025907 jun Genes Proteins 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 238000007169 ligase reaction Methods 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 208000002502 lymphedema Diseases 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 229910001425 magnesium ion Inorganic materials 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 235000009973 maize Nutrition 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000013178 mathematical model Methods 0.000 description 1
- 210000004914 menses Anatomy 0.000 description 1
- 230000006609 metabolic stress Effects 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 108091086416 miR-192 stem-loop Proteins 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 108010084677 myogenic factor 6 Proteins 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 230000030147 nuclear export Effects 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 210000001819 pancreatic juice Anatomy 0.000 description 1
- 210000004912 pericardial fluid Anatomy 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003905 phosphatidylinositols Chemical class 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 210000004910 pleural fluid Anatomy 0.000 description 1
- 125000005575 polycyclic aromatic hydrocarbon group Chemical group 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 150000004032 porphyrins Chemical class 0.000 description 1
- 229910001414 potassium ion Inorganic materials 0.000 description 1
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 229940097325 prolactin Drugs 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 210000004908 prostatic fluid Anatomy 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 230000004850 protein–protein interaction Effects 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 210000004915 pus Anatomy 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 102000016914 ras Proteins Human genes 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 1
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000028617 response to DNA damage stimulus Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 238000012340 reverse transcriptase PCR Methods 0.000 description 1
- 239000003161 ribonuclease inhibitor Substances 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 102220198225 rs1057519923 Human genes 0.000 description 1
- 102220190200 rs139796716 Human genes 0.000 description 1
- 102200075811 rs587777233 Human genes 0.000 description 1
- 102220044582 rs587781412 Human genes 0.000 description 1
- 102220029418 rs62642053 Human genes 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- COFLCBMDHTVQRA-UHFFFAOYSA-N sapphyrin Chemical compound N1C(C=2NC(C=C3N=C(C=C4NC(=C5)C=C4)C=C3)=CC=2)=CC=C1C=C1C=CC5=N1 COFLCBMDHTVQRA-UHFFFAOYSA-N 0.000 description 1
- 238000007423 screening assay Methods 0.000 description 1
- 210000002374 sebum Anatomy 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 229940055619 selenocysteine Drugs 0.000 description 1
- 235000016491 selenocysteine Nutrition 0.000 description 1
- ZKZBPNGNEQAJSX-UHFFFAOYSA-N selenocysteine Natural products [SeH]CC(N)C(O)=O ZKZBPNGNEQAJSX-UHFFFAOYSA-N 0.000 description 1
- JRPHGDYSKGJTKZ-UHFFFAOYSA-N selenophosphoric acid Chemical class OP(O)([SeH])=O JRPHGDYSKGJTKZ-UHFFFAOYSA-N 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 230000009919 sequestration Effects 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 230000037432 silent mutation Effects 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 210000003802 sputum Anatomy 0.000 description 1
- 208000024794 sputum Diseases 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000011272 standard treatment Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 108020001568 subdomains Proteins 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 210000004243 sweat Anatomy 0.000 description 1
- 210000001179 synovial fluid Anatomy 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 108010050301 tRNA nucleotidyltransferase Proteins 0.000 description 1
- 210000001138 tear Anatomy 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 239000012581 transferrin Substances 0.000 description 1
- 230000017105 transposition Effects 0.000 description 1
- 239000013638 trimer Substances 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 108010087967 type I signal peptidase Proteins 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 108010027510 vaccinia virus capping enzyme Proteins 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 210000004916 vomit Anatomy 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/7105—Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/711—Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
- A61K48/0058—Nucleic acids adapted for tissue specific expression, e.g. having tissue specific promoters as part of a contruct
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]
- C12N2310/141—MicroRNAs, miRNAs
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Zoology (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Toxicology (AREA)
- Gastroenterology & Hepatology (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Applications Claiming Priority (15)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361753661P | 2013-01-17 | 2013-01-17 | |
| US61/753,661 | 2013-01-17 | ||
| US201361754159P | 2013-01-18 | 2013-01-18 | |
| US61/754,159 | 2013-01-18 | ||
| US201361781097P | 2013-03-14 | 2013-03-14 | |
| US61/781,097 | 2013-03-14 | ||
| US201361829334P | 2013-05-31 | 2013-05-31 | |
| US61/829,334 | 2013-05-31 | ||
| US201361839893P | 2013-06-27 | 2013-06-27 | |
| US61/839,893 | 2013-06-27 | ||
| US201361842733P | 2013-07-03 | 2013-07-03 | |
| US61/842,733 | 2013-07-03 | ||
| US201361857304P | 2013-07-23 | 2013-07-23 | |
| US61/857,304 | 2013-07-23 | ||
| PCT/US2013/062531 WO2014113089A2 (en) | 2013-01-17 | 2013-09-30 | Signal-sensor polynucleotides for the alteration of cellular phenotypes |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2897941A1 true CA2897941A1 (en) | 2014-07-24 |
Family
ID=49448268
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2897941A Abandoned CA2897941A1 (en) | 2013-01-17 | 2013-09-30 | Signal-sensor polynucleotides for the alteration of cellular phenotypes |
Country Status (7)
| Country | Link |
|---|---|
| US (4) | US20140200261A1 (OSRAM) |
| EP (2) | EP2946014A2 (OSRAM) |
| JP (3) | JP2016504050A (OSRAM) |
| AU (2) | AU2013374345A1 (OSRAM) |
| CA (1) | CA2897941A1 (OSRAM) |
| HK (1) | HK1217215A1 (OSRAM) |
| WO (1) | WO2014113089A2 (OSRAM) |
Families Citing this family (161)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3318248B1 (en) | 2009-12-01 | 2019-04-10 | Translate Bio, Inc. | Delivery of mrna for the augmentation of proteins and enzymes in human genetic diseases |
| WO2012019168A2 (en) | 2010-08-06 | 2012-02-09 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
| ES3005233T3 (en) | 2010-10-01 | 2025-03-14 | Modernatx Inc | Modified nucleosides, nucleotides, and nucleic acids, and uses thereof |
| WO2012075040A2 (en) | 2010-11-30 | 2012-06-07 | Shire Human Genetic Therapies, Inc. | mRNA FOR USE IN TREATMENT OF HUMAN GENETIC DISEASES |
| DE12722942T1 (de) | 2011-03-31 | 2021-09-30 | Modernatx, Inc. | Freisetzung und formulierung von manipulierten nukleinsäuren |
| EP2717893B1 (en) | 2011-06-08 | 2019-05-08 | Translate Bio, Inc. | Lipid nanoparticle compositions and methods for mrna delivery |
| AU2012352180A1 (en) | 2011-12-16 | 2014-07-31 | Moderna Therapeutics, Inc. | Modified nucleoside, nucleotide, and nucleic acid compositions |
| US10704021B2 (en) | 2012-03-15 | 2020-07-07 | Flodesign Sonics, Inc. | Acoustic perfusion devices |
| US9283287B2 (en) | 2012-04-02 | 2016-03-15 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of nuclear proteins |
| US9254311B2 (en) | 2012-04-02 | 2016-02-09 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of proteins |
| US9572897B2 (en) | 2012-04-02 | 2017-02-21 | Modernatx, Inc. | Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins |
| WO2013151663A1 (en) | 2012-04-02 | 2013-10-10 | modeRNA Therapeutics | Modified polynucleotides for the production of membrane proteins |
| KR20220051197A (ko) | 2012-05-17 | 2022-04-26 | 익스텐드 바이오사이언시즈, 인크. | 개선된 약물 전달용 캐리어 |
| WO2013185069A1 (en) | 2012-06-08 | 2013-12-12 | Shire Human Genetic Therapies, Inc. | Pulmonary delivery of mrna to non-lung target cells |
| WO2013185067A1 (en) | 2012-06-08 | 2013-12-12 | Shire Human Genetic Therapies, Inc. | Nuclease resistant polynucleotides and uses thereof |
| EP2885419A4 (en) | 2012-08-14 | 2016-05-25 | Moderna Therapeutics Inc | ENZYMES AND POLYMERASES FOR RNA SYNTHESIS |
| HRP20220607T1 (hr) | 2012-11-26 | 2022-06-24 | Modernatx, Inc. | Terminalno modificirana rna |
| EP2946014A2 (en) | 2013-01-17 | 2015-11-25 | Moderna Therapeutics, Inc. | Signal-sensor polynucleotides for the alteration of cellular phenotypes |
| EP2968391A1 (en) | 2013-03-13 | 2016-01-20 | Moderna Therapeutics, Inc. | Long-lived polynucleotide molecules |
| TR201901310T4 (tr) | 2013-03-14 | 2019-02-21 | Translate Bio Inc | Mesajcı RNA'nın saflaştırılması yöntemleri. |
| EP2971010B1 (en) | 2013-03-14 | 2020-06-10 | ModernaTX, Inc. | Formulation and delivery of modified nucleoside, nucleotide, and nucleic acid compositions |
| LT2968586T (lt) | 2013-03-14 | 2018-11-26 | Translate Bio, Inc. | Cft mrnr kompozicijos bei su jomis susiję būdai ir panaudojimai |
| JP6399560B2 (ja) | 2013-03-14 | 2018-10-03 | トランスレイト バイオ， インコーポレイテッド | ｍＲＮＡによってコードされる抗体を送達するための方法及び組成物 |
| DK2972360T3 (en) | 2013-03-15 | 2018-05-22 | Translate Bio Inc | SYNERGISTIC IMPROVEMENT OF DELIVERY OF NUCLEIC ACIDS THROUGH MIXED FORMULATIONS |
| US10138507B2 (en) | 2013-03-15 | 2018-11-27 | Modernatx, Inc. | Manufacturing methods for production of RNA transcripts |
| US10590161B2 (en) | 2013-03-15 | 2020-03-17 | Modernatx, Inc. | Ion exchange purification of mRNA |
| US10077439B2 (en) | 2013-03-15 | 2018-09-18 | Modernatx, Inc. | Removal of DNA fragments in mRNA production process |
| EP4279610A3 (en) | 2013-03-15 | 2024-01-03 | ModernaTX, Inc. | Ribonucleic acid purification |
| SI3019619T1 (sl) | 2013-07-11 | 2021-12-31 | Modernatx, Inc. | Sestave, ki zajemajo sintetične polinukleotide, ki kodirajo proteine, pozvezane s crispr, in sintetične sgrna, ter metode uporabe |
| EP3052106A4 (en) | 2013-09-30 | 2017-07-19 | ModernaTX, Inc. | Polynucleotides encoding immune modulating polypeptides |
| EP3052511A4 (en) | 2013-10-02 | 2017-05-31 | Moderna Therapeutics, Inc. | Polynucleotide molecules and uses thereof |
| KR20160067219A (ko) | 2013-10-03 | 2016-06-13 | 모더나 세라퓨틱스, 인코포레이티드 | 저밀도 지단백질 수용체를 암호화하는 폴리뉴클레오타이드 |
| EP3574923A1 (en) | 2013-10-22 | 2019-12-04 | Translate Bio, Inc. | Mrna therapy for phenylketonuria |
| CN105658800A (zh) | 2013-10-22 | 2016-06-08 | 夏尔人类遗传性治疗公司 | Mrna的cns递送及其用途 |
| CN112618732A (zh) | 2013-10-22 | 2021-04-09 | 夏尔人类遗传性治疗公司 | 用于递送信使rna的脂质制剂 |
| BR112016009014B1 (pt) | 2013-10-22 | 2024-02-06 | Translate Bio, Inc | USO DE COMPOSIÇÃO COMPREENDENDO mRNA PARA DEFICIÊNCIA DE ARGININOSSUCINATO SINTETASE |
| EP3092049A1 (en) | 2014-01-08 | 2016-11-16 | Flodesign Sonics Inc. | Acoustophoresis device with dual acoustophoretic chamber |
| KR102739894B1 (ko) | 2014-04-25 | 2024-12-05 | 샤이어 휴먼 지네틱 테라피즈 인크. | 메신저 rna 의 정제 방법 |
| US10022455B2 (en) | 2014-05-30 | 2018-07-17 | Translate Bio, Inc. | Biodegradable lipids for delivery of nucleic acids |
| BR112016029634A2 (pt) | 2014-06-18 | 2017-10-24 | Nat Cancer Ct | kit, dispositivo e método para a detecção de câncer de fígado |
| WO2015196128A2 (en) | 2014-06-19 | 2015-12-23 | Moderna Therapeutics, Inc. | Alternative nucleic acid molecules and uses thereof |
| CN111588695A (zh) | 2014-06-24 | 2020-08-28 | 川斯勒佰尔公司 | 用于递送核酸的立体化学富集组合物 |
| BR112016030852A2 (pt) | 2014-07-02 | 2018-01-16 | Shire Human Genetic Therapies | encapsulação de rna mensageiro |
| US10407683B2 (en) | 2014-07-16 | 2019-09-10 | Modernatx, Inc. | Circular polynucleotides |
| US20170210788A1 (en) | 2014-07-23 | 2017-07-27 | Modernatx, Inc. | Modified polynucleotides for the production of intrabodies |
| US20180085391A1 (en) * | 2014-08-08 | 2018-03-29 | Modernatx, Inc. | Compositions and methods for the treatment of ophthalmic diseases and conditions |
| WO2016065042A1 (en) | 2014-10-22 | 2016-04-28 | Extend Biosciences, Inc. | Therapeutic vitamin d conjugates |
| WO2016065052A1 (en) | 2014-10-22 | 2016-04-28 | Extend Biosciences, Inc. | Insulin vitamin d conjugates |
| US9789197B2 (en) | 2014-10-22 | 2017-10-17 | Extend Biosciences, Inc. | RNAi vitamin D conjugates |
| WO2016069752A1 (en) * | 2014-10-29 | 2016-05-06 | University Of Houston System | Nanovectors for penetrating brain tumor tissues to conduct gene therapy |
| WO2016090262A1 (en) | 2014-12-05 | 2016-06-09 | Shire Human Genetic Therapies, Inc. | Messenger rna therapy for treatment of articular disease |
| WO2016100812A1 (en) * | 2014-12-19 | 2016-06-23 | Moderna Therapeutics, Inc. | Terminal modifications of polynucleotides |
| WO2016130572A2 (en) * | 2015-02-10 | 2016-08-18 | Dana-Farber Cancer Institute, Inc. | Methods of determining levels of exposure to radiation and uses thereof |
| AU2016233135B2 (en) | 2015-03-19 | 2021-07-08 | Translate Bio, Inc. | mRNA therapy for pompe disease |
| EP3318630B1 (en) * | 2015-04-22 | 2020-11-04 | iPS Academia Japan, Inc. | Method for sorting tissue cells |
| US11708572B2 (en) | 2015-04-29 | 2023-07-25 | Flodesign Sonics, Inc. | Acoustic cell separation techniques and processes |
| US11377651B2 (en) | 2016-10-19 | 2022-07-05 | Flodesign Sonics, Inc. | Cell therapy processes utilizing acoustophoresis |
| ES2875589T3 (es) * | 2015-05-15 | 2021-11-10 | Curevac Ag | Regímenes de sensibilización-refuerzo que implican la administración de al menos un constructo de ARNm |
| EP3307305A4 (en) * | 2015-06-10 | 2019-05-22 | Modernatx, Inc. | TARGETED ADAPTIVE VACCINES |
| EP4101930A1 (en) | 2015-09-17 | 2022-12-14 | ModernaTX, Inc. | Polynucleotides containing a stabilizing tail region |
| US11434486B2 (en) | 2015-09-17 | 2022-09-06 | Modernatx, Inc. | Polynucleotides containing a morpholino linker |
| US10849920B2 (en) | 2015-10-05 | 2020-12-01 | Modernatx, Inc. | Methods for therapeutic administration of messenger ribonucleic acid drugs |
| CA3001852A1 (en) | 2015-10-14 | 2017-04-20 | Translate Bio, Inc. | Modification of rna-related enzymes for enhanced production |
| KR101737706B1 (ko) | 2015-12-15 | 2017-05-18 | 한국원자력의학원 | miR-5582-5p를 포함하는 항암제 |
| JP7065036B2 (ja) * | 2015-12-17 | 2022-05-11 | モダーナティエックス・インコーポレイテッド | メチルマロニルＣｏＡムターゼをコードするポリヌクレオチド |
| HRP20220525T1 (hr) | 2015-12-23 | 2022-05-27 | Modernatx, Inc. | Postupci uporabe polinukleotida koji kodiraju ligand ox40 |
| CN105483233B (zh) * | 2015-12-24 | 2018-07-20 | 北京大学第一医院 | 检测miR-3158-5p表达量的系统在预测阿司匹林对心血管疾病患者疗效中的应用 |
| US11021756B2 (en) * | 2016-01-04 | 2021-06-01 | Yang Zuozhang | MiRNA markers for the diagnosis of osteosarcoma |
| US20210206818A1 (en) | 2016-01-22 | 2021-07-08 | Modernatx, Inc. | Messenger ribonucleic acids for the production of intracellular binding polypeptides and methods of use thereof |
| US20200330606A1 (en) * | 2016-03-29 | 2020-10-22 | Valkyrie Therapeutics Inc. | Modulation of structural maintenance of chromosome-1 expression |
| DK3436589T3 (da) * | 2016-03-31 | 2020-11-23 | Ethris Gmbh | Ny minimale utr-sekvenser |
| WO2017177169A1 (en) | 2016-04-08 | 2017-10-12 | Rana Therapeutics, Inc. | Multimeric coding nucleic acid and uses thereof |
| WO2017190061A1 (en) * | 2016-04-29 | 2017-11-02 | The University Of Chicago | Synthetic dna binding domain peptides and uses thereof |
| US11214789B2 (en) | 2016-05-03 | 2022-01-04 | Flodesign Sonics, Inc. | Concentration and washing of particles with acoustics |
| PT3458474T (pt) * | 2016-05-18 | 2022-11-08 | Modernatx Inc | Combinações de arnm que codificam polipéptidos de modulação imunitária e as suas utilizações |
| WO2017201328A1 (en) | 2016-05-18 | 2017-11-23 | Modernatx, Inc. | POLYNUCLEOTIDES ENCODING α-GALACTOSIDASE A FOR THE TREATMENT OF FABRY DISEASE |
| US12128113B2 (en) | 2016-05-18 | 2024-10-29 | Modernatx, Inc. | Polynucleotides encoding JAGGED1 for the treatment of Alagille syndrome |
| MA45036A (fr) | 2016-05-18 | 2019-03-27 | Modernatx Inc | Polynucléotides codant pour la citrine pour le traitement de la citrullinémie de type 2 |
| WO2017201348A1 (en) | 2016-05-18 | 2017-11-23 | Modernatx, Inc. | Polynucleotides encoding galactose-1-phosphate uridylyltransferase for the treatment of galactosemia type 1 |
| CN109195621A (zh) | 2016-05-18 | 2019-01-11 | 莫得纳特斯公司 | 编码白细胞介素12(il12)的多核苷酸及其用途 |
| JP2019519516A (ja) | 2016-05-18 | 2019-07-11 | モデルナティーエックス， インコーポレイテッド | がんの治療のためのｍＲＮＡ併用療法 |
| WO2017201346A1 (en) | 2016-05-18 | 2017-11-23 | Modernatx, Inc. | Polynucleotides encoding porphobilinogen deaminase for the treatment of acute intermittent porphyria |
| US20190298657A1 (en) | 2016-05-18 | 2019-10-03 | Modernatx, Inc. | Polynucleotides Encoding Acyl-CoA Dehydrogenase, Very Long-Chain for the Treatment of Very Long-Chain Acyl-CoA Dehydrogenase Deficiency |
| AU2017276806A1 (en) * | 2016-06-07 | 2018-12-20 | Garvan Institute Of Medical Research | Methods of treating neuroblastoma and reagents therefor |
| EP3842530A1 (en) | 2016-06-13 | 2021-06-30 | Translate Bio, Inc. | Messenger rna therapy for the treatment of ornithine transcarbamylase deficiency |
| JP2019525901A (ja) | 2016-06-14 | 2019-09-12 | モデルナティエックス インコーポレイテッドＭｏｄｅｒｎａＴＸ，Ｉｎｃ． | 脂質ナノ粒子の安定化製剤 |
| US12385034B2 (en) | 2016-06-24 | 2025-08-12 | Modernatx, Inc. | Methods and apparatus for filtration |
| CN109526226A (zh) | 2016-07-07 | 2019-03-26 | 鲁比厄斯治疗法股份有限公司 | 与表达外源rna的治疗性细胞体系有关的组合物和方法 |
| WO2018018077A1 (en) * | 2016-07-25 | 2018-02-01 | Garvan Institute Of Medical Research | Methods of treating breast cancer and reagents therefor |
| RU2765874C2 (ru) | 2016-10-26 | 2022-02-04 | МОДЕРНАТиЭкс, ИНК. | Матричные рибонуклеиновые кислоты для усиления иммунных ответов и способы их применения |
| US11583504B2 (en) | 2016-11-08 | 2023-02-21 | Modernatx, Inc. | Stabilized formulations of lipid nanoparticles |
| WO2018094964A1 (zh) * | 2016-11-25 | 2018-05-31 | 武汉大学 | 一种以凋亡信号调节激酶1n端二聚化为靶点筛选用于治疗脂肪性肝炎药物的方法 |
| EP3576780A1 (en) | 2017-02-01 | 2019-12-11 | Modernatx, Inc. | Immunomodulatory therapeutic mrna compositions encoding activating oncogene mutation peptides |
| EP3585417B1 (en) | 2017-02-27 | 2023-02-22 | Translate Bio, Inc. | Method of making a codon-optimized cftr mrna |
| US11629340B2 (en) | 2017-03-03 | 2023-04-18 | Obsidian Therapeutics, Inc. | DHFR tunable protein regulation |
| JP2020513824A (ja) | 2017-03-24 | 2020-05-21 | キュアバック アーゲー | Ｃｒｉｓｐｒ関連タンパク質をコードする核酸、及びその使用 |
| WO2018193119A1 (en) * | 2017-04-21 | 2018-10-25 | Ospedale San Raffaele S.R.L. | Gene therapy |
| CA3063531A1 (en) | 2017-05-16 | 2018-11-22 | Translate Bio, Inc. | Treatment of cystic fibrosis by delivery of codon-optimized mrna encoding cftr |
| EP3625246A1 (en) | 2017-05-18 | 2020-03-25 | ModernaTX, Inc. | Polynucleotides encoding tethered interleukin-12 (il12) polypeptides and uses thereof |
| WO2018213789A1 (en) | 2017-05-18 | 2018-11-22 | Modernatx, Inc. | Modified messenger rna comprising functional rna elements |
| EP3647422B1 (en) * | 2017-06-29 | 2024-07-24 | Toray Industries, Inc. | Kit, device, and method for lung cancer detection |
| US20210079440A1 (en) * | 2017-07-12 | 2021-03-18 | Kyoto University | HIGH EXPRESSION mRNA SWITCH |
| WO2019046809A1 (en) | 2017-08-31 | 2019-03-07 | Modernatx, Inc. | METHODS OF MANUFACTURING LIPID NANOPARTICLES |
| JP2021507561A (ja) | 2017-12-14 | 2021-02-22 | フロデザイン ソニックス， インク．Ｆｌｏｄｅｓｉｇｎ Ｓｏｎｉｃｓ， Ｉｎｃ． | 音響トランスデューサドライバ及びコントローラ |
| MA51306A (fr) | 2017-12-20 | 2020-10-28 | Translate Bio Inc | Compositions et procédés améliorés pour le traitement du déficit en ornithine transcarbamylase |
| WO2019152557A1 (en) | 2018-01-30 | 2019-08-08 | Modernatx, Inc. | Compositions and methods for delivery of agents to immune cells |
| KR102141124B1 (ko) * | 2018-01-30 | 2020-08-04 | (주)바이오니아 | 이중 가닥 miRNA를 포함하는 이중나선 올리고뉴클레오타이드 구조체 및 이의 용도 |
| KR102070969B1 (ko) * | 2018-04-10 | 2020-01-29 | 한국한의학연구원 | 통증 판별용 마커 |
| WO2019199974A1 (en) * | 2018-04-10 | 2019-10-17 | Onconetics Pharmaceuticals, Inc. | Microrna regulated expression vectors, methods of making, and uses thereof |
| EP3773745A1 (en) | 2018-04-11 | 2021-02-17 | ModernaTX, Inc. | Messenger rna comprising functional rna elements |
| JP7462227B2 (ja) * | 2018-04-25 | 2024-04-05 | 東レ株式会社 | 膀胱がんの検出のためのキット、デバイス及び方法 |
| CN108760700A (zh) * | 2018-05-29 | 2018-11-06 | 云南健牛生物科技有限公司 | 一种荧光金纳米簇的制备及用于四环素及铜荧光探针 |
| MX2021001517A (es) | 2018-08-08 | 2021-04-19 | Theramir Ltd | Terapia basada en microarn dirigida contra canceres positivos para proteina citosolica de linfocito 1 (lcp-1). |
| CA3108544A1 (en) | 2018-08-24 | 2020-02-27 | Translate Bio, Inc. | Methods for purification of messenger rna |
| MX2021002418A (es) * | 2018-08-30 | 2021-04-28 | Univ North Carolina Chapel Hill | Genes sinteticos activados por retroalimentacion, casetes de coincidencia de semilla objetivo y sus usos. |
| AU2019338535A1 (en) | 2018-09-14 | 2021-04-15 | Modernatx, Inc. | Methods and compositions for treating cancer using mRNA therapeutics |
| WO2020061457A1 (en) | 2018-09-20 | 2020-03-26 | Modernatx, Inc. | Preparation of lipid nanoparticles and methods of administration thereof |
| CN109439749B (zh) * | 2018-09-26 | 2022-06-24 | 北京恩泽康泰生物科技有限公司 | 用于结直肠癌诊断的外泌体miRNA标志物及诊断试剂盒 |
| WO2020102609A1 (en) * | 2018-11-15 | 2020-05-22 | The Trustees Of The University Of Pennsylvania | Compositions and methods for the cytoplasmic delivery of antibodies and other proteins |
| CA3120647A1 (en) | 2018-11-21 | 2020-05-28 | Translate Bio, Inc. | Treatment of cystic fibrosis by delivery of nebulized mrna encoding cftr |
| US12042527B2 (en) | 2019-01-08 | 2024-07-23 | Modernatx, Inc. | Use of mRNAs encoding OX40L, IL-23 and IL-36gamma in combination with immune checkpoint blockade for treating particular cancers |
| CA3128215A1 (en) | 2019-01-31 | 2020-08-06 | Modernatx, Inc. | Methods of preparing lipid nanoparticles |
| WO2020210535A1 (en) | 2019-04-09 | 2020-10-15 | The University Of Chicago | Versatile peptide and protein macrocyclization and multimerization with diels-alder cycloadditions |
| AU2020268388A1 (en) | 2019-05-07 | 2021-12-02 | Modernatx, Inc. | Polynucleotides for disrupting immune cell activity and methods of use thereof |
| EP3981473A4 (en) * | 2019-06-05 | 2023-06-28 | Cancerstem Tech Inc. | Therapeutic agent for cancer |
| AU2020296104A1 (en) * | 2019-06-21 | 2022-01-27 | Quralis Corporation | PPM1A inhibitors and methods of using same |
| WO2020263985A1 (en) | 2019-06-24 | 2020-12-30 | Modernatx, Inc. | Messenger rna comprising functional rna elements and uses thereof |
| MA56539A (fr) | 2019-06-24 | 2022-04-27 | Modernatx Inc | Arn messager résistant à l'endonucléase et utilisations correspondantes |
| CN110628907B (zh) * | 2019-09-09 | 2023-01-24 | 张宝华 | 一组胆囊癌血浆外泌体microRNAs标记物及其应用 |
| CN110845596B (zh) * | 2019-11-15 | 2021-09-03 | 上海交通大学 | 突变体xSUMO及其相关产品 |
| CN113134010B (zh) * | 2020-01-20 | 2023-09-01 | 上海市生物医药技术研究院 | 一种靶向雌激素受体α的微小RNA及其抗肿瘤用途 |
| JP2023513043A (ja) | 2020-01-31 | 2023-03-30 | モデルナティエックス インコーポレイテッド | 脂質ナノ粒子を調製する方法 |
| CN111440802A (zh) * | 2020-03-16 | 2020-07-24 | 复旦大学附属妇产科医院 | 一种用于表达rp11-395g23.3的序列及其构建体和构建方法与应用 |
| CN114774540B (zh) * | 2020-03-30 | 2025-07-04 | 中国医学科学院肿瘤医院 | 包括外泌体miR-106b-3p、miR-330-5p等在肺癌诊断中的应用 |
| KR20220160602A (ko) * | 2020-03-31 | 2022-12-06 | 도레이 카부시키가이샤 | 해마 위축을 검출하기 위한 키트 또는 디바이스 및 방법 |
| JP2023526059A (ja) | 2020-05-14 | 2023-06-20 | モダーナティエックス・インコーポレイテッド | ｍＲＮＡ治療薬及びエフェクター分子を含むＬＮＰ組成物 |
| KR20230042005A (ko) | 2020-06-23 | 2023-03-27 | 모더나티엑스, 인크. | 반감기가 연장된 mrna 치료제를 포함하는 lnp 조성물 |
| US20230248042A1 (en) * | 2020-07-10 | 2023-08-10 | Societe Des Produits Nestle S.A. | Nutritional composition comprising mir-3184 |
| US20230277457A1 (en) | 2020-08-06 | 2023-09-07 | Modernatx, Inc. | Methods of preparing lipid nanoparticles |
| CN113234778A (zh) * | 2020-08-20 | 2021-08-10 | 深圳市瑞吉生物科技有限公司 | 一种Cap2结构5′帽子类似物及其制备方法和应用 |
| WO2022174079A1 (en) | 2021-02-12 | 2022-08-18 | Modernatx, Inc. | Lnp compositions comprising payloads for in vivo therapy |
| WO2022233880A1 (en) | 2021-05-03 | 2022-11-10 | Curevac Ag | Improved nucleic acid sequence for cell type specific expression |
| EP4355882A2 (en) | 2021-06-15 | 2024-04-24 | Modernatx, Inc. | Engineered polynucleotides for cell-type or microenvironment-specific expression |
| EP4365288A4 (en) * | 2021-06-30 | 2025-03-12 | Kyowa Kirin Co., Ltd. | POLYNUCLEOTIDE AND MEDICINAL COMPOSITION |
| WO2023064469A1 (en) | 2021-10-13 | 2023-04-20 | Modernatx, Inc. | Compositions of mrna-encoded il15 fusion proteins and methods of use thereof |
| CN114107347B (zh) * | 2021-11-24 | 2022-10-28 | 中国人民解放军空军军医大学 | 一种基于具有按需抗炎功能、装载炎症响应型mRNA的工程化外泌体及其构建方法和应用 |
| CN114854740B (zh) * | 2022-03-29 | 2024-03-15 | 南京医科大学 | miR-483-5p海绵体及在制备抑制2型糖尿病β细胞去分化的药物中的用途 |
| US12325881B2 (en) * | 2022-04-04 | 2025-06-10 | Agency For Science, Technology And Research | Method of determining and treating breast cancer |
| WO2024026475A1 (en) | 2022-07-29 | 2024-02-01 | Modernatx, Inc. | Compositions for delivery to hematopoietic stem and progenitor cells (hspcs) and related uses |
| US20250375391A1 (en) | 2022-07-29 | 2025-12-11 | Modernatx, Inc. | Lipid nanoparticle compositions comprising surface lipid derivatives and relates uses |
| US20250375389A1 (en) | 2022-07-29 | 2025-12-11 | Modernatx, Inc. | Lipid nanoparticle compositions comprising phospholipid derivatives and related uses |
| JP2025534350A (ja) | 2022-09-30 | 2025-10-15 | エクステンド バイオサイエンシズ インコーポレーテッド | 長時間作用型副甲状腺ホルモン |
| CN115261482B (zh) * | 2022-10-08 | 2022-12-09 | 暨南大学 | miR-4256在胃癌治疗、诊断以及预后评估中的应用 |
| CN115869332A (zh) * | 2022-10-27 | 2023-03-31 | 北京新合睿恩生物医疗科技有限公司 | 递送至体内后在肝脏少表达的mRNA药物及其制备方法 |
| WO2024178305A1 (en) | 2023-02-24 | 2024-08-29 | Modernatx, Inc. | Compositions of mrna-encoded il-15 fusion proteins and methods of use thereof for treating cancer |
| CN116286628B (zh) * | 2023-05-15 | 2023-07-28 | 四川大学华西医院 | 一种牙髓间充质干细胞培养基添加物、培养基及其应用 |
| WO2024259373A1 (en) | 2023-06-14 | 2024-12-19 | Modernatx, Inc. | Compounds and compositions for delivery of therapeutic agents |
| WO2025160381A1 (en) | 2024-01-26 | 2025-07-31 | Modernatx, Inc. | Methods of preparing lipid nanoparticles |
| WO2025166202A1 (en) | 2024-01-31 | 2025-08-07 | Modernatx, Inc. | Lipid nanoparticle compositions comprising sialic acid derivatives and the uses thereof |
| WO2025184429A1 (en) | 2024-02-28 | 2025-09-04 | Modernatx, Inc. | Bromodomain and extra-terminal domain (bet) epigenetic reader decoy |
| WO2025194138A1 (en) | 2024-03-14 | 2025-09-18 | Tessera Therapeutics, Inc. | St1cas9 compositions and methods for modulating a genome |
Family Cites Families (300)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2588623A (en) | 1948-05-10 | 1952-03-11 | Eliscu Frank | Surgical instrument for intradermal injection of fluids |
| US3467096A (en) | 1966-04-12 | 1969-09-16 | Ferrell S Horn | Multiple hypodermic syringe arrangement |
| US3572336A (en) | 1968-04-30 | 1971-03-23 | Daniel R Hershberg | Syringe |
| US4270537A (en) | 1979-11-19 | 1981-06-02 | Romaine Richard A | Automatic hypodermic syringe |
| JPS5927900A (ja) | 1982-08-09 | 1984-02-14 | Wakunaga Seiyaku Kk | 固定化オリゴヌクレオチド |
| FR2540122B1 (fr) | 1983-01-27 | 1985-11-29 | Centre Nat Rech Scient | Nouveaux composes comportant une sequence d'oligonucleotide liee a un agent d'intercalation, leur procede de synthese et leur application |
| US4605735A (en) | 1983-02-14 | 1986-08-12 | Wakunaga Seiyaku Kabushiki Kaisha | Oligonucleotide derivatives |
| US4948882A (en) | 1983-02-22 | 1990-08-14 | Syngene, Inc. | Single-stranded labelled oligonucleotides, reactive monomers and methods of synthesis |
| US4824941A (en) | 1983-03-10 | 1989-04-25 | Julian Gordon | Specific antibody to the native form of 2'5'-oligonucleotides, the method of preparation and the use as reagents in immunoassays or for binding 2'5'-oligonucleotides in biological systems |
| US4587044A (en) | 1983-09-01 | 1986-05-06 | The Johns Hopkins University | Linkage of proteins to nucleic acids |
| US5118800A (en) | 1983-12-20 | 1992-06-02 | California Institute Of Technology | Oligonucleotides possessing a primary amino group in the terminal nucleotide |
| US5118802A (en) | 1983-12-20 | 1992-06-02 | California Institute Of Technology | DNA-reporter conjugates linked via the 2' or 5'-primary amino group of the 5'-terminal nucleoside |
| FR2567892B1 (fr) | 1984-07-19 | 1989-02-17 | Centre Nat Rech Scient | Nouveaux oligonucleotides, leur procede de preparation et leurs applications comme mediateurs dans le developpement des effets des interferons |
| US5258506A (en) | 1984-10-16 | 1993-11-02 | Chiron Corporation | Photolabile reagents for incorporation into oligonucleotide chains |
| US5430136A (en) | 1984-10-16 | 1995-07-04 | Chiron Corporation | Oligonucleotides having selectably cleavable and/or abasic sites |
| US4828979A (en) | 1984-11-08 | 1989-05-09 | Life Technologies, Inc. | Nucleotide analogs for nucleic acid labeling and detection |
| US5034506A (en) | 1985-03-15 | 1991-07-23 | Anti-Gene Development Group | Uncharged morpholino-based polymers having achiral intersubunit linkages |
| US4596556A (en) | 1985-03-25 | 1986-06-24 | Bioject, Inc. | Hypodermic injection apparatus |
| US4762779A (en) | 1985-06-13 | 1988-08-09 | Amgen Inc. | Compositions and methods for functionalizing nucleic acids |
| US5317098A (en) | 1986-03-17 | 1994-05-31 | Hiroaki Shizuya | Non-radioisotope tagging of fragments |
| US4695273A (en) | 1986-04-08 | 1987-09-22 | I-Flow Corporation | Multiple needle holder and subcutaneous multiple channel infusion port |
| JPS638396A (ja) | 1986-06-30 | 1988-01-14 | Wakunaga Pharmaceut Co Ltd | ポリ標識化オリゴヌクレオチド誘導体 |
| CA1283827C (en) | 1986-12-18 | 1991-05-07 | Giorgio Cirelli | Appliance for injection of liquid formulations |
| GB8704027D0 (en) | 1987-02-20 | 1987-03-25 | Owen Mumford Ltd | Syringe needle combination |
| US4904582A (en) | 1987-06-11 | 1990-02-27 | Synthetic Genetics | Novel amphiphilic nucleic acid conjugates |
| US4940460A (en) | 1987-06-19 | 1990-07-10 | Bioject, Inc. | Patient-fillable and non-invasive hypodermic injection device assembly |
| US4941880A (en) | 1987-06-19 | 1990-07-17 | Bioject, Inc. | Pre-filled ampule and non-invasive hypodermic injection device assembly |
| US4790824A (en) | 1987-06-19 | 1988-12-13 | Bioject, Inc. | Non-invasive hypodermic injection device |
| US5585481A (en) | 1987-09-21 | 1996-12-17 | Gen-Probe Incorporated | Linking reagents for nucleotide probes |
| US5525465A (en) | 1987-10-28 | 1996-06-11 | Howard Florey Institute Of Experimental Physiology And Medicine | Oligonucleotide-polyamide conjugates and methods of production and applications of the same |
| DE3738460A1 (de) | 1987-11-12 | 1989-05-24 | Max Planck Gesellschaft | Modifizierte oligonukleotide |
| US5082830A (en) | 1988-02-26 | 1992-01-21 | Enzo Biochem, Inc. | End labeled nucleotide probe |
| US5339163A (en) | 1988-03-16 | 1994-08-16 | Canon Kabushiki Kaisha | Automatic exposure control device using plural image plane detection areas |
| US5109124A (en) | 1988-06-01 | 1992-04-28 | Biogen, Inc. | Nucleic acid probe linked to a label having a terminal cysteine |
| US5262536A (en) | 1988-09-15 | 1993-11-16 | E. I. Du Pont De Nemours And Company | Reagents for the preparation of 5'-tagged oligonucleotides |
| FR2638359A1 (fr) | 1988-11-03 | 1990-05-04 | Tino Dalto | Guide de seringue avec reglage de la profondeur de penetration de l'aiguille dans la peau |
| US5512439A (en) | 1988-11-21 | 1996-04-30 | Dynal As | Oligonucleotide-linked magnetic particles and uses thereof |
| US5599923A (en) | 1989-03-06 | 1997-02-04 | Board Of Regents, University Of Tx | Texaphyrin metal complexes having improved functionalization |
| US5457183A (en) | 1989-03-06 | 1995-10-10 | Board Of Regents, The University Of Texas System | Hydroxylated texaphyrins |
| US5391723A (en) | 1989-05-31 | 1995-02-21 | Neorx Corporation | Oligonucleotide conjugates |
| US4958013A (en) | 1989-06-06 | 1990-09-18 | Northwestern University | Cholesteryl modified oligonucleotides |
| US5451463A (en) | 1989-08-28 | 1995-09-19 | Clontech Laboratories, Inc. | Non-nucleoside 1,3-diol reagents for labeling synthetic oligonucleotides |
| US5254469A (en) | 1989-09-12 | 1993-10-19 | Eastman Kodak Company | Oligonucleotide-enzyme conjugate that can be used as a probe in hybridization assays and polymerase chain reaction procedures |
| US5591722A (en) | 1989-09-15 | 1997-01-07 | Southern Research Institute | 2'-deoxy-4'-thioribonucleosides and their antiviral activity |
| JPH05504552A (ja) | 1989-10-24 | 1993-07-15 | ギリアド サイエンシズ，インコーポレイテッド | ２’位が改変されたオリゴヌクレオチド |
| US5208020A (en) | 1989-10-25 | 1993-05-04 | Immunogen Inc. | Cytotoxic agents comprising maytansinoids and their therapeutic use |
| US5312335A (en) | 1989-11-09 | 1994-05-17 | Bioject Inc. | Needleless hypodermic injection device |
| US5064413A (en) | 1989-11-09 | 1991-11-12 | Bioject, Inc. | Needleless hypodermic injection device |
| US5292873A (en) | 1989-11-29 | 1994-03-08 | The Research Foundation Of State University Of New York | Nucleic acids labeled with naphthoquinone probe |
| US5486603A (en) | 1990-01-08 | 1996-01-23 | Gilead Sciences, Inc. | Oligonucleotide having enhanced binding affinity |
| US6783931B1 (en) | 1990-01-11 | 2004-08-31 | Isis Pharmaceuticals, Inc. | Amine-derivatized nucleosides and oligonucleosides |
| US5646265A (en) | 1990-01-11 | 1997-07-08 | Isis Pharmceuticals, Inc. | Process for the preparation of 2'-O-alkyl purine phosphoramidites |
| US5670633A (en) | 1990-01-11 | 1997-09-23 | Isis Pharmaceuticals, Inc. | Sugar modified oligonucleotides that detect and modulate gene expression |
| US7037646B1 (en) | 1990-01-11 | 2006-05-02 | Isis Pharmaceuticals, Inc. | Amine-derivatized nucleosides and oligonucleosides |
| US5578718A (en) | 1990-01-11 | 1996-11-26 | Isis Pharmaceuticals, Inc. | Thiol-derivatized nucleosides |
| WO1991013080A1 (en) | 1990-02-20 | 1991-09-05 | Gilead Sciences, Inc. | Pseudonucleosides and pseudonucleotides and their polymers |
| US5214136A (en) | 1990-02-20 | 1993-05-25 | Gilead Sciences, Inc. | Anthraquinone-derivatives oligonucleotides |
| GB9009980D0 (en) | 1990-05-03 | 1990-06-27 | Amersham Int Plc | Phosphoramidite derivatives,their preparation and the use thereof in the incorporation of reporter groups on synthetic oligonucleotides |
| DK0455905T3 (da) | 1990-05-11 | 1998-12-07 | Microprobe Corp | Dipsticks til nukleinsyrehybridiseringsassays og fremgangsmåde til kovalent immobilisering af oligonukleotider |
| US5608046A (en) | 1990-07-27 | 1997-03-04 | Isis Pharmaceuticals, Inc. | Conjugated 4'-desmethyl nucleoside analog compounds |
| US5688941A (en) | 1990-07-27 | 1997-11-18 | Isis Pharmaceuticals, Inc. | Methods of making conjugated 4' desmethyl nucleoside analog compounds |
| US5489677A (en) | 1990-07-27 | 1996-02-06 | Isis Pharmaceuticals, Inc. | Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms |
| US5138045A (en) | 1990-07-27 | 1992-08-11 | Isis Pharmaceuticals | Polyamine conjugated oligonucleotides |
| US5602240A (en) | 1990-07-27 | 1997-02-11 | Ciba Geigy Ag. | Backbone modified oligonucleotide analogs |
| US5218105A (en) | 1990-07-27 | 1993-06-08 | Isis Pharmaceuticals | Polyamine conjugated oligonucleotides |
| US5245022A (en) | 1990-08-03 | 1993-09-14 | Sterling Drug, Inc. | Exonuclease resistant terminally substituted oligonucleotides |
| US5190521A (en) | 1990-08-22 | 1993-03-02 | Tecnol Medical Products, Inc. | Apparatus and method for raising a skin wheal and anesthetizing skin |
| US5512667A (en) | 1990-08-28 | 1996-04-30 | Reed; Michael W. | Trifunctional intermediates for preparing 3'-tailed oligonucleotides |
| ATE198598T1 (de) | 1990-11-08 | 2001-01-15 | Hybridon Inc | Verbindung von mehrfachreportergruppen auf synthetischen oligonukleotiden |
| US5527288A (en) | 1990-12-13 | 1996-06-18 | Elan Medical Technologies Limited | Intradermal drug delivery device and method for intradermal delivery of drugs |
| US5539082A (en) | 1993-04-26 | 1996-07-23 | Nielsen; Peter E. | Peptide nucleic acids |
| US5719262A (en) | 1993-11-22 | 1998-02-17 | Buchardt, Deceased; Ole | Peptide nucleic acids having amino acid side chains |
| US5714331A (en) | 1991-05-24 | 1998-02-03 | Buchardt, Deceased; Ole | Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility |
| US5371241A (en) | 1991-07-19 | 1994-12-06 | Pharmacia P-L Biochemicals Inc. | Fluorescein labelled phosphoramidites |
| GB9118204D0 (en) | 1991-08-23 | 1991-10-09 | Weston Terence E | Needle-less injector |
| SE9102652D0 (sv) | 1991-09-13 | 1991-09-13 | Kabi Pharmacia Ab | Injection needle arrangement |
| ES2103918T3 (es) | 1991-10-17 | 1997-10-01 | Ciba Geigy Ag | Nucleosidos biciclicos, oligonucleotidos, procedimiento para su obtencion y productos intermedios. |
| US5359044A (en) | 1991-12-13 | 1994-10-25 | Isis Pharmaceuticals | Cyclobutyl oligonucleotide surrogates |
| US5565552A (en) | 1992-01-21 | 1996-10-15 | Pharmacyclics, Inc. | Method of expanded porphyrin-oligonucleotide conjugate synthesis |
| US5595726A (en) | 1992-01-21 | 1997-01-21 | Pharmacyclics, Inc. | Chromophore probe for detection of nucleic acid |
| FR2687679B1 (fr) | 1992-02-05 | 1994-10-28 | Centre Nat Rech Scient | Oligothionucleotides. |
| US5328483A (en) | 1992-02-27 | 1994-07-12 | Jacoby Richard M | Intradermal injection device with medication and needle guard |
| DK0563475T3 (da) | 1992-03-25 | 2000-09-18 | Immunogen Inc | Konjugater af cellebindende midler og derivater af CC-1065 |
| EP0577558A2 (de) | 1992-07-01 | 1994-01-05 | Ciba-Geigy Ag | Carbocyclische Nukleoside mit bicyclischen Ringen, Oligonukleotide daraus, Verfahren zu deren Herstellung, deren Verwendung und Zwischenproduckte |
| US5272250A (en) | 1992-07-10 | 1993-12-21 | Spielvogel Bernard F | Boronated phosphoramidate compounds |
| US5383851A (en) | 1992-07-24 | 1995-01-24 | Bioject Inc. | Needleless hypodermic injection device |
| US5569189A (en) | 1992-09-28 | 1996-10-29 | Equidyne Systems, Inc. | hypodermic jet injector |
| US5334144A (en) | 1992-10-30 | 1994-08-02 | Becton, Dickinson And Company | Single use disposable needleless injector |
| US5574142A (en) | 1992-12-15 | 1996-11-12 | Microprobe Corporation | Peptide linkers for improved oligonucleotide delivery |
| RU2123492C1 (ru) | 1993-02-19 | 1998-12-20 | Ниппон Синяку Ко., Лтд | Производные глицерина, средство для доставки физиологически активного вещества и фармацевтическая композиция |
| DK0691968T3 (da) | 1993-03-30 | 1998-02-23 | Sanofi Sa | Acykliske nukleosid-analoge og oligonukleotidsekvenser indeholdende disse |
| DE4311944A1 (de) | 1993-04-10 | 1994-10-13 | Degussa | Umhüllte Natriumpercarbonatpartikel, Verfahren zu deren Herstellung und sie enthaltende Wasch-, Reinigungs- und Bleichmittelzusammensetzungen |
| US6294664B1 (en) | 1993-07-29 | 2001-09-25 | Isis Pharmaceuticals, Inc. | Synthesis of oligonucleotides |
| US5446137B1 (en) | 1993-12-09 | 1998-10-06 | Behringwerke Ag | Oligonucleotides containing 4'-substituted nucleotides |
| US5519134A (en) | 1994-01-11 | 1996-05-21 | Isis Pharmaceuticals, Inc. | Pyrrolidine-containing monomers and oligomers |
| WO1995024176A1 (en) | 1994-03-07 | 1995-09-14 | Bioject, Inc. | Ampule filling device |
| US5466220A (en) | 1994-03-08 | 1995-11-14 | Bioject, Inc. | Drug vial mixing and transfer device |
| US5627053A (en) | 1994-03-29 | 1997-05-06 | Ribozyme Pharmaceuticals, Inc. | 2'deoxy-2'-alkylnucleotide containing nucleic acid |
| US5464395A (en) | 1994-04-05 | 1995-11-07 | Faxon; David P. | Catheter for delivering therapeutic and/or diagnostic agents to the tissue surrounding a bodily passageway |
| US5597696A (en) | 1994-07-18 | 1997-01-28 | Becton Dickinson And Company | Covalent cyanine dye oligonucleotide conjugates |
| US5580731A (en) | 1994-08-25 | 1996-12-03 | Chiron Corporation | N-4 modified pyrimidine deoxynucleotides and oligonucleotide probes synthesized therewith |
| US5597909A (en) | 1994-08-25 | 1997-01-28 | Chiron Corporation | Polynucleotide reagents containing modified deoxyribose moieties, and associated methods of synthesis and use |
| US5599302A (en) | 1995-01-09 | 1997-02-04 | Medi-Ject Corporation | Medical injection system and method, gas spring thereof and launching device using gas spring |
| US5795587A (en) | 1995-01-23 | 1998-08-18 | University Of Pittsburgh | Stable lipid-comprising drug delivery complexes and methods for their production |
| US5730723A (en) | 1995-10-10 | 1998-03-24 | Visionary Medical Products Corporation, Inc. | Gas pressured needle-less injection device and method |
| US5713863A (en) | 1996-01-11 | 1998-02-03 | Interventional Technologies Inc. | Catheter with fluid medication injectors |
| US5893397A (en) | 1996-01-12 | 1999-04-13 | Bioject Inc. | Medication vial/syringe liquid-transfer apparatus |
| US5994316A (en) | 1996-02-21 | 1999-11-30 | The Immune Response Corporation | Method of preparing polynucleotide-carrier complexes for delivery to cells |
| GB9607549D0 (en) | 1996-04-11 | 1996-06-12 | Weston Medical Ltd | Spring-powered dispensing device |
| US20030073908A1 (en) | 1996-04-26 | 2003-04-17 | 2000 Injectx, Inc. | Method and apparatus for delivery of genes, enzymes and biological agents to tissue cells |
| EP0925088A2 (en) | 1996-06-28 | 1999-06-30 | Sontra Medical, L.P. | Ultrasound enhancement of transdermal transport |
| US6576752B1 (en) | 1997-02-14 | 2003-06-10 | Isis Pharmaceuticals, Inc. | Aminooxy functionalized oligomers |
| JP3756313B2 (ja) | 1997-03-07 | 2006-03-15 | 武 今西 | 新規ビシクロヌクレオシド及びオリゴヌクレオチド類縁体 |
| US6761726B1 (en) | 1998-05-15 | 2004-07-13 | Pyng Medical Corp. | Method and apparatus for the intraosseous introduction of a device such as an infusion tube |
| US5993412A (en) | 1997-05-19 | 1999-11-30 | Bioject, Inc. | Injection apparatus |
| US6794499B2 (en) | 1997-09-12 | 2004-09-21 | Exiqon A/S | Oligonucleotide analogues |
| WO1999014346A2 (en) * | 1997-09-19 | 1999-03-25 | Sequitur, Inc. | SENSE mRNA THERAPY |
| US6077251A (en) | 1997-10-30 | 2000-06-20 | Ting; Windsor | Medicinal agent administration system |
| JP2001521759A (ja) | 1997-11-12 | 2001-11-13 | ザ ブリガム アンド ウィメンズ ホスピタル，インコーポレイテッド | ヒトアミロイド前駆体タンパク質遺伝子の翻訳エンハンサーエレメント |
| US6548633B1 (en) | 1998-12-22 | 2003-04-15 | Genset, S.A. | Complementary DNA's encoding proteins with signal peptides |
| AU1819499A (en) | 1997-12-12 | 1999-06-28 | Samyang Corporation | Positively-charged poly{alpha-(omega-aminoalkyl)glycolic acid} for the delivery of a bioactive agent via tissue and cellular uptake |
| US6517869B1 (en) | 1997-12-12 | 2003-02-11 | Expression Genetics, Inc. | Positively charged poly(alpha-(omega-aminoalkyl)lycolic acid) for the delivery of a bioactive agent via tissue and cellular uptake |
| US6320017B1 (en) | 1997-12-23 | 2001-11-20 | Inex Pharmaceuticals Corp. | Polyamide oligomers |
| US6190315B1 (en) | 1998-01-08 | 2001-02-20 | Sontra Medical, Inc. | Sonophoretic enhanced transdermal transport |
| IT1298087B1 (it) | 1998-01-08 | 1999-12-20 | Fiderm S R L | Dispositivo per il controllo della profondita' di penetrazione di un ago, in particolare applicabile ad una siringa per iniezioni |
| US8287483B2 (en) | 1998-01-08 | 2012-10-16 | Echo Therapeutics, Inc. | Method and apparatus for enhancement of transdermal transport |
| AU4193199A (en) | 1998-05-20 | 1999-12-06 | Expression Genetics, Inc. | A hepatocyte targeting polyethylene glyco-grafted poly-l-lysine polymeric gene carrier |
| CA2337680A1 (en) | 1998-07-13 | 2000-01-20 | Expression Genetics, Inc. | Polyester analogue of poly-l-lysine as a soluble, biodegradable gene delivery carrier |
| US20040171980A1 (en) | 1998-12-18 | 2004-09-02 | Sontra Medical, Inc. | Method and apparatus for enhancement of transdermal transport |
| DE60035861T2 (de) | 1999-03-01 | 2008-04-24 | Cytyc Corp., Marlborough | Geräte, methoden und kits für die gleichzeitige austragung von substanzen in mehrere milchkanäle der brust |
| US7084125B2 (en) | 1999-03-18 | 2006-08-01 | Exiqon A/S | Xylo-LNA analogues |
| CN102180924A (zh) | 1999-05-04 | 2011-09-14 | 桑塔里斯制药公司 | L-核糖-lna类似物 |
| US7171264B1 (en) | 1999-05-10 | 2007-01-30 | Genetronics, Inc. | Intradermal delivery of active agents by needle-free injection and electroporation |
| US6743211B1 (en) | 1999-11-23 | 2004-06-01 | Georgia Tech Research Corporation | Devices and methods for enhanced microneedle penetration of biological barriers |
| CA2311201A1 (en) | 1999-08-05 | 2001-02-05 | Genset S.A. | Ests and encoded human proteins |
| US6551338B1 (en) | 1999-09-01 | 2003-04-22 | Mcgill University | Method and device for myogenesis and angiogenesis of the heart |
| SE515932C2 (sv) | 1999-12-23 | 2001-10-29 | Prostalund Operations Ab | Sätt och anordning vid behandling av prostata |
| US7468275B2 (en) | 2000-01-28 | 2008-12-23 | The Scripps Research Institute | Synthetic internal ribosome entry sites and methods of identifying same |
| EP1259602A1 (en) | 2000-01-28 | 2002-11-27 | The Scripps Research Institute | Methods of identifying synthetic transcriptional and translational regulatory elements, and compositions relating to same |
| US6468247B1 (en) | 2000-04-21 | 2002-10-22 | Mark Zamoyski | Perfusion device for localized drug delivery |
| US6537242B1 (en) | 2000-06-06 | 2003-03-25 | Becton, Dickinson And Company | Method and apparatus for enhancing penetration of a member for the intradermal sampling or administration of a substance |
| US6607513B1 (en) | 2000-06-08 | 2003-08-19 | Becton, Dickinson And Company | Device for withdrawing or administering a substance and method of manufacturing a device |
| US20050181033A1 (en) | 2000-06-29 | 2005-08-18 | Dekker John P.Iii | Method for delivering interferons to the intradermal compartment |
| US20040142474A1 (en) | 2000-09-14 | 2004-07-22 | Expression Genetics, Inc. | Novel cationic lipopolymer as a biocompatible gene delivery agent |
| US6696038B1 (en) | 2000-09-14 | 2004-02-24 | Expression Genetics, Inc. | Cationic lipopolymer as biocompatible gene delivery agent |
| AU2001293687A1 (en) | 2000-10-04 | 2002-04-15 | Cureon A/S | Improved synthesis of purine locked nucleic acid analogues |
| US7628780B2 (en) | 2001-01-13 | 2009-12-08 | Medtronic, Inc. | Devices and methods for interstitial injection of biologic agents into tissue |
| US6652886B2 (en) | 2001-02-16 | 2003-11-25 | Expression Genetics | Biodegradable cationic copolymers of poly (alkylenimine) and poly (ethylene glycol) for the delivery of bioactive agents |
| US6625486B2 (en) | 2001-04-11 | 2003-09-23 | Advanced Cardiovascular Systems, Inc. | Method and apparatus for intracellular delivery of an agent |
| EP1800697B1 (de) | 2001-06-05 | 2010-04-14 | CureVac GmbH | Stabilisierte mRNA mit erhöhtem G/C-Gehalt für die Gentherapie |
| CA2451816A1 (en) | 2001-06-29 | 2003-01-09 | Becton, Dickinson And Company | Intradermal delivery of vaccines and gene therapeutic agents via microcannula |
| US6586524B2 (en) | 2001-07-19 | 2003-07-01 | Expression Genetics, Inc. | Cellular targeting poly(ethylene glycol)-grafted polymeric gene carrier |
| EP2428568B1 (en) | 2001-09-28 | 2018-04-25 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Microrna molecules |
| US7429258B2 (en) | 2001-10-26 | 2008-09-30 | Massachusetts Institute Of Technology | Microneedle transport device |
| US7585491B2 (en) | 2002-12-13 | 2009-09-08 | Immunomedics, Inc. | Immunoconjugates with an intracellularly-cleavable linkage |
| CA2484265C (en) | 2002-05-06 | 2012-08-07 | Becton, Dickinson And Company | Method and device for controlling drug pharmacokinetics |
| EP1503716A4 (en) | 2002-05-08 | 2007-07-04 | Univ California | SYSTEM AND METHOD FOR THE TREATMENT OF CARDIAC ARCHITECTURES WITH FIBROBLASTED CELLS |
| US7374930B2 (en) | 2002-05-21 | 2008-05-20 | Expression Genetics, Inc. | GLP-1 gene delivery for the treatment of type 2 diabetes |
| US20040009180A1 (en) | 2002-07-11 | 2004-01-15 | Allergan, Inc. | Transdermal botulinum toxin compositions |
| EP2020208B1 (en) | 2002-08-01 | 2015-03-04 | Abbott Laboratories Vascular Enterprises Limited | Injection of an inflammatory substance to seal a puncture wound |
| US20040136992A1 (en) * | 2002-08-28 | 2004-07-15 | Burton Paul B. J. | Compositions and method for treating cardiovascular disease |
| CA2497086A1 (en) | 2002-08-30 | 2004-03-11 | Becton, Dickinson And Company | Method of controlling pharmacokinetics of immunomodulatory compounds |
| US6896666B2 (en) | 2002-11-08 | 2005-05-24 | Kochamba Family Trust | Cutaneous injection delivery under suction |
| KR20050115231A (ko) * | 2003-02-10 | 2005-12-07 | 내셔날 인스티튜트 오브 어드밴스드 인더스트리얼 사이언스 앤드 테크놀로지 | 포유동물 세포의 조절 |
| US20040226556A1 (en) | 2003-05-13 | 2004-11-18 | Deem Mark E. | Apparatus for treating asthma using neurotoxin |
| CA2533701A1 (en) | 2003-07-31 | 2005-02-17 | Isis Pharmaceuticals, Inc. | Oligomeric compounds and compositions for use in modulation of small non-coding rnas |
| US7998119B2 (en) | 2003-11-18 | 2011-08-16 | Nano Pass Technologies Ltd. | System and method for delivering fluid into flexible biological barrier |
| US7150726B2 (en) | 2004-01-23 | 2006-12-19 | Norfolk Medical | Device for subcutaneous infusion of fluids |
| WO2005072710A2 (en) | 2004-01-28 | 2005-08-11 | Johns Hopkins University | Drugs and gene carrier particles that rapidly move through mucous barriers |
| US8882717B2 (en) | 2004-04-12 | 2014-11-11 | Allergan, Inc. | Multi-site injection system |
| US20080103053A1 (en) | 2005-11-22 | 2008-05-01 | Helicos Biosciences Corporation | Methods and compositions for sequencing a nucleic acid |
| US8338648B2 (en) | 2004-06-12 | 2012-12-25 | Signum Biosciences, Inc. | Topical compositions and methods for epithelial-related conditions |
| US7527947B2 (en) | 2004-06-14 | 2009-05-05 | Novozymes A/S | Signal peptide for producing a polypeptide |
| JP2008505685A (ja) | 2004-07-06 | 2008-02-28 | トランスファーマ メディカル リミテッド | 経皮免疫処置用送達システム |
| JPWO2006028245A1 (ja) | 2004-09-07 | 2008-05-08 | 河淳株式会社 | 商品自動前出し棚装置 |
| US8057821B2 (en) | 2004-11-03 | 2011-11-15 | Egen, Inc. | Biodegradable cross-linked cationic multi-block copolymers for gene delivery and methods of making thereof |
| WO2006054280A2 (en) | 2004-11-18 | 2006-05-26 | Nanopass Technologies Ltd. | System and method for delivering fluid into flexible biological barrier |
| US7964571B2 (en) | 2004-12-09 | 2011-06-21 | Egen, Inc. | Combination of immuno gene therapy and chemotherapy for treatment of cancer and hyperproliferative diseases |
| CA2590098C (en) | 2004-12-10 | 2015-03-31 | Justin Hanes | Functionalized poly (ether-anhydride) block copolymers |
| US20060263338A1 (en) | 2005-03-04 | 2006-11-23 | Jacoby Douglas B | Catheter-based delivery of Skeletal Myoblasts to the Myocardium of Damaged Hearts |
| JP4793806B2 (ja) | 2005-03-22 | 2011-10-12 | Ｔｔｉ・エルビュー株式会社 | イオントフォレーシス装置 |
| CN101203611B (zh) * | 2005-04-19 | 2013-08-14 | 巴斯福植物科学有限公司 | 控制基因表达的改良方法 |
| US7850656B2 (en) | 2005-04-29 | 2010-12-14 | Warsaw Orthopedic, Inc. | Devices and methods for delivering medical agents |
| SI2002003T1 (sl) | 2005-05-27 | 2016-05-31 | Ospedale San Raffaele S.R.L. | Genski vektor, ki vsebuje mi-RNA |
| US7691086B2 (en) | 2005-06-14 | 2010-04-06 | Tengiz Tkebuchava | Catheter for introduction of medications to the tissues of a heart or other organ |
| JP5015923B2 (ja) | 2005-06-30 | 2012-09-05 | アーケミックス コーポレイション | 完全な２’改変核酸転写物を生成するための材料および方法 |
| US8101385B2 (en) | 2005-06-30 | 2012-01-24 | Archemix Corp. | Materials and methods for the generation of transcripts comprising modified nucleotides |
| EP4174179B1 (en) | 2005-08-23 | 2025-05-07 | The Trustees of the University of Pennsylvania | Rna containing modified nucleosides and methods of use thereof |
| EP2479254A1 (en) | 2005-08-24 | 2012-07-25 | The Scripps Research Institute | Translation enhancer-element dependent vector systems |
| US20070185432A1 (en) | 2005-09-19 | 2007-08-09 | Transport Pharmaceuticals, Inc. | Electrokinetic system and method for delivering methotrexate |
| DE102005046490A1 (de) | 2005-09-28 | 2007-03-29 | Johannes-Gutenberg-Universität Mainz | Modifikationen von RNA, die zu einer erhöhten Transkriptstabilität und Translationseffizienz führen |
| US8012096B2 (en) | 2005-10-17 | 2011-09-06 | Cardiogenesis Corporation | Surgical device and method for performing combination revascularization and therapeutic substance delivery to tissue |
| EP2591794A1 (en) | 2006-01-05 | 2013-05-15 | The Ohio State University Research Foundation | MicroRNA expressions abnormalities in pancreatic endocrine and acinar tumors |
| EP2479286B1 (en) | 2006-01-05 | 2013-11-13 | The Ohio State University Research Foundation | MicroRNA-based methods and compositions for the diagnosis and treatment of solid cancers |
| CN102908630B (zh) | 2006-01-27 | 2014-11-19 | Isis制药公司 | 6-修饰的双环核酸类似物 |
| AU2007223311C1 (en) | 2006-03-02 | 2013-06-20 | The Board Of Regents Of The University Of Oklahoma | MicroRNA expression profile associated with pancreatic cancer |
| US7361908B2 (en) | 2006-04-13 | 2008-04-22 | The Hong Kong Polytechnic University | Radiation dose estimation for radiochromic films based on measurements at multiple absorption peaks |
| US20100215580A1 (en) | 2006-09-08 | 2010-08-26 | The Johns Hopkins University | Compositions and methods for enhancing transport through mucus |
| EP2073735B1 (en) | 2006-09-08 | 2010-11-24 | Arbel Medical Ltd. | Device for combined treatment |
| AU2007299828C1 (en) | 2006-09-19 | 2014-07-17 | Interpace Diagnostics, Llc | MicroRNAs differentially expressed in pancreatic diseases and uses thereof |
| AU2007314212B2 (en) | 2006-11-01 | 2014-05-29 | The Govt. Of The Usa As Represented By The Secretary Of The Department Of Health And Human Services | MicroRNA expression signature for predicting survival and metastases in Hepatocellular carcinoma |
| CN101622349A (zh) | 2006-12-08 | 2010-01-06 | 奥斯瑞根公司 | 作为治疗性干预靶标的miR-21调节的基因和途径 |
| EP2207891B1 (en) | 2006-12-22 | 2012-07-25 | Archemix LLC | Materials and methods for the generation of transcripts comprising modified nucleotides |
| US8057426B2 (en) | 2007-01-03 | 2011-11-15 | Medtronic Vascular, Inc. | Devices and methods for injection of multiple-component therapies |
| WO2008091799A2 (en) * | 2007-01-22 | 2008-07-31 | The Trustees Of Columbia University In The City Of New York | Cell-based methods for identifying inhibitors of parkinson's disease-associated lrrk2 mutants |
| US8029496B2 (en) | 2007-03-05 | 2011-10-04 | Ebrahim Versi | Method and device for delivering drug to the trigone of the bladder |
| KR101211252B1 (ko) | 2007-04-27 | 2012-12-12 | 에코 테라퓨틱스, 인크. | 경피 피분석물 감지 또는 경피 약제 전달용 피부 침투장치 |
| US8415096B2 (en) | 2007-05-23 | 2013-04-09 | University Of South Florida | Micro-RNAs modulating immunity and inflammation |
| US20090099034A1 (en) | 2007-06-07 | 2009-04-16 | Wisconsin Alumni Research Foundation | Reagents and Methods for miRNA Expression Analysis and Identification of Cancer Biomarkers |
| WO2009015071A1 (en) * | 2007-07-23 | 2009-01-29 | Dharmacon, Inc. | Screening of micro-rna cluster inhibitor pools |
| US20090042825A1 (en) | 2007-08-06 | 2009-02-12 | Majed Matar | Composition, method of preparation & application of concentrated formulations of condensed nucleic acids with a cationic lipopolymer |
| CA2696209C (en) | 2007-08-14 | 2016-10-25 | Fred Hutchinson Cancer Research Center | Needle array assembly and method for delivering therapeutic agents |
| US20130108663A1 (en) | 2007-09-14 | 2013-05-02 | Vrije Universiteit Brussel | Enhancing the t-cell stimulatory capacity of human antigen presenting cells in vitro and in vivo and their use in vaccination |
| US20090137945A1 (en) | 2007-11-28 | 2009-05-28 | Claire Marquez | Electro Collagen Induction Therapy Device |
| EP2225396A4 (en) | 2007-11-30 | 2011-03-02 | Univ Ohio State Res Found | PROFILING AND SCREENING OF MICRO-RNA EXPRESSION IN PERIPHERAL BLOOD IN LUNG CANCER |
| SG10201408165WA (en) | 2007-12-11 | 2015-01-29 | Scripps Research Inst | Compositions and methods related to mrna translational enhancer elements |
| WO2009093384A1 (ja) * | 2008-01-24 | 2009-07-30 | National Institute Of Advanced Industrial Science And Technology | ポリヌクレオチド及びポリヌクレオチド類似体並びにこれらを用いた遺伝子発現制御方法 |
| WO2009100430A2 (en) | 2008-02-08 | 2009-08-13 | Asuragen, Inc | miRNAs DIFFERENTIALLY EXPRESSED IN LYMPH NODES FROM CANCER PATIENTS |
| CN102015027A (zh) | 2008-02-28 | 2011-04-13 | 俄亥俄州立大学研究基金会 | 与人慢性淋巴细胞性白血病(ccl)相关的微rna特征和其用途 |
| US20100004313A1 (en) | 2008-02-29 | 2010-01-07 | Tbd | Modified Poloxamers for Gene Expression and Associated Methods |
| EP2271699A1 (en) | 2008-03-14 | 2011-01-12 | Egen, Inc. | Biodegradable cross-linked branched poly (alkylene imines) |
| EP2112235A1 (en) | 2008-04-24 | 2009-10-28 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Compositions and methods for microRNA expression profiling of nasopharyngeal carcinoma |
| US9394538B2 (en) * | 2008-05-07 | 2016-07-19 | Shi-Lung Lin | Development of universal cancer drugs and vaccines |
| EP2433664B1 (en) | 2008-06-06 | 2016-08-10 | Wockhardt Limited | A device for delivery of biological material |
| US7799016B2 (en) | 2008-06-20 | 2010-09-21 | Pharmaco-Kinesis Corporation | Magnetic breather pump and a method for treating a brain tumor using the same |
| US9913806B2 (en) | 2008-06-25 | 2018-03-13 | Fe3 Medical, Inc. | Patches and methods for the transdermal delivery of a therapeutically effective amount of iron |
| US20100009424A1 (en) | 2008-07-14 | 2010-01-14 | Natasha Forde | Sonoporation systems and methods |
| WO2010018563A2 (en) | 2008-08-12 | 2010-02-18 | Rosetta Genomics Ltd. | Compositions and methods for the prognosis of lymphoma |
| US8357118B2 (en) | 2008-08-26 | 2013-01-22 | Cook Medical Technologies Llc | Balloon catheters having a plurality of needles for the injection of one or more therapeutic agents |
| WO2010027903A2 (en) * | 2008-09-08 | 2010-03-11 | Fred Hutchinson Cancer Research Center | Lung cancer diagnosis |
| US9801722B2 (en) | 2008-10-10 | 2017-10-31 | Peter Forsell | Infusion of drugs |
| ITVI20080239A1 (it) | 2008-10-14 | 2010-04-15 | Antoine Assaf | Apparato medicale per iniezioni multiple. |
| JP5791505B2 (ja) | 2008-10-20 | 2015-10-07 | アルナイラム ファーマシューティカルズ， インコーポレイテッドＡｌｎｙｌａｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． | トランスチレチンの発現を阻害するための組成物および方法 |
| EP2364362B1 (en) | 2008-11-12 | 2015-10-21 | Ospedale San Raffaele S.r.l. | Gene vector for inducing transgene-specific immune tolerance |
| WO2010066384A1 (en) | 2008-12-10 | 2010-06-17 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Compositions and methods for micro-rna expression profiling of cancer stem cells |
| US8669085B2 (en) | 2009-02-05 | 2014-03-11 | Ut-Battelle, Llc | Transformation of gram positive bacteria by sonoporation |
| CN102438978B (zh) | 2009-03-20 | 2017-02-22 | Clsn实验室股份有限公司 | 聚胺衍生物 |
| US20120264626A1 (en) | 2009-05-08 | 2012-10-18 | The Ohio State University Research Foundation | MicroRNA Expression Profiling and Targeting in Chronic Obstructive Pulmonary Disease (COPD) Lung Tissue and Methods of Use Thereof |
| PL2440183T3 (pl) | 2009-06-10 | 2019-01-31 | Arbutus Biopharma Corporation | Ulepszona formulacja lipidowa |
| CA2767225A1 (en) | 2009-07-06 | 2011-01-13 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for enhancing production of a biological product |
| EP3165234B1 (de) | 2009-07-31 | 2019-04-03 | ethris GmbH | Rna mit einer kombination aus unmodifizierten und modifizierten nucleotiden zur proteinexpression |
| WO2011028175A1 (en) | 2009-09-01 | 2011-03-10 | Agency For Science, Technology And Research | Terminal device and method for processing an encrypted bit stream |
| EP3318248B1 (en) | 2009-12-01 | 2019-04-10 | Translate Bio, Inc. | Delivery of mrna for the augmentation of proteins and enzymes in human genetic diseases |
| WO2011076807A2 (en) | 2009-12-23 | 2011-06-30 | Novartis Ag | Lipids, lipid compositions, and methods of using them |
| WO2011076142A1 (en) | 2009-12-24 | 2011-06-30 | Fudan University | Compositions and methods for microrna expession profiling in plasma of colorectal cancer |
| WO2011076143A1 (en) | 2009-12-24 | 2011-06-30 | Fudan University | Compositions and methods for microrna expression profiling of lung cancer |
| EP2341145A1 (en) | 2009-12-30 | 2011-07-06 | febit holding GmbH | miRNA fingerprint in the diagnosis of diseases |
| WO2011088309A1 (en) * | 2010-01-14 | 2011-07-21 | Regulus Therapeutics Inc. | Microrna compositions and methods |
| WO2011094683A2 (en) | 2010-01-29 | 2011-08-04 | H. Lee Moffitt Cancer Center And Research Institute, Inc. | Method of identifying myelodysplastic syndromes |
| EP2354246A1 (en) | 2010-02-05 | 2011-08-10 | febit holding GmbH | miRNA in the diagnosis of ovarian cancer |
| US20130059015A1 (en) | 2010-03-11 | 2013-03-07 | H. Lee Moffitt Cancer Center & Research Institute | Human Cancer micro-RNA Expression Profiles Predictive of Chemo-Response |
| US9149432B2 (en) | 2010-03-19 | 2015-10-06 | Massachusetts Institute Of Technology | Lipid vesicle compositions and methods of use |
| JP5652830B2 (ja) * | 2010-04-09 | 2015-01-14 | 国立大学法人 東京大学 | マイクロｒｎａ制御組換えワクシニアウイルス及びその使用 |
| WO2011130624A2 (en) | 2010-04-16 | 2011-10-20 | Immune Disease Institute, Inc. | Sustained polypeptide expression from synthetic, modified rnas and uses thereof |
| US9629979B2 (en) | 2010-04-28 | 2017-04-25 | Sanovas, Inc. | Pressure/Vacuum actuated catheter drug delivery probe |
| WO2011157294A1 (en) | 2010-06-16 | 2011-12-22 | Universita' Degli Studi Di Padova | Compositions for use in treating or preventing cancer, breast cancer, lung cancer, ovarian cancer, metastasis, heart failure, cardiac remodelling, dilated cardiomyopathy, autoimmune diseases, or diseases or disorders related thereto |
| US20120158100A1 (en) | 2010-06-21 | 2012-06-21 | Kevin Schomacker | Driving Microneedle Arrays into Skin and Delivering RF Energy |
| US8351828B2 (en) | 2010-06-30 | 2013-01-08 | Eastman Kodak Company | Printer having an alternate scavenger geometry |
| US8353871B2 (en) | 2010-07-05 | 2013-01-15 | Roller Jet Ltd. | Drug delivery device with needles and roller |
| CA2804396C (en) | 2010-07-06 | 2021-06-29 | Novartis Ag | Liposomes with lipids having an advantageous pka-value for rna delivery |
| AU2011276236B2 (en) | 2010-07-06 | 2016-03-10 | Glaxosmithkline Biologicals S.A. | Cationic oil-in-water emulsions |
| US11291635B2 (en) | 2010-07-06 | 2022-04-05 | Glaxosmithkline Biological Sa | Virion-like delivery particles for self-replicating RNA molecules |
| US20130230884A1 (en) | 2010-07-16 | 2013-09-05 | John Chaput | Methods to Identify Synthetic and Natural RNA Elements that Enhance Protein Translation |
| WO2012019168A2 (en) | 2010-08-06 | 2012-02-09 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
| WO2012019630A1 (en) | 2010-08-13 | 2012-02-16 | Curevac Gmbh | Nucleic acid comprising or coding for a histone stem-loop and a poly(a) sequence or a polyadenylation signal for increasing the expression of an encoded protein |
| SI3981427T1 (sl) | 2010-08-31 | 2022-08-31 | Glaxosmithkline Biologicals S.A. | Pegilirani liposomi za dostavo imunogen-kodirajoče RNA |
| US20130189351A1 (en) | 2010-08-31 | 2013-07-25 | Novartis Ag | Lipids suitable for liposomal delivery of protein coding rna |
| ES3005233T3 (en) | 2010-10-01 | 2025-03-14 | Modernatx Inc | Modified nucleosides, nucleotides, and nucleic acids, and uses thereof |
| WO2013086505A1 (en) | 2011-12-09 | 2013-06-13 | Vanderbilt University | Integrated organ-on-chip system and applications of the same |
| WO2012061703A1 (en) | 2010-11-05 | 2012-05-10 | The Johns Hopkins University | Compositions and methods relating to reduced mucoadhesion |
| US10364440B2 (en) | 2011-01-04 | 2019-07-30 | Brown University | Nanotubes as carriers of nucleic acids into cells |
| AU2012207606B2 (en) | 2011-01-11 | 2017-02-23 | Alnylam Pharmaceuticals, Inc. | Pegylated lipids and their use for drug delivery |
| WO2012099805A2 (en) | 2011-01-19 | 2012-07-26 | Ocean Nanotech, Llc | Nanoparticle based immunological stimulation |
| DE12722942T1 (de) * | 2011-03-31 | 2021-09-30 | Modernatx, Inc. | Freisetzung und formulierung von manipulierten nukleinsäuren |
| US10086043B2 (en) | 2011-04-03 | 2018-10-02 | The General Hospital Corporation | Efficient protein expression in vivo using modified RNA (MOD-RNA) |
| US20140113978A1 (en) | 2011-05-01 | 2014-04-24 | University Of Rochester | Multifocal hepatocellular carcinoma microrna expression patterns and uses thereof |
| EP2944961A1 (en) | 2011-05-06 | 2015-11-18 | XenTech | Markers for cancer prognosis and therapy and methods of use |
| ES2610245T3 (es) | 2011-07-15 | 2017-04-26 | Leo Pharma A/S | Perfilado de microARN para el diagnóstico en linfoma cutáneo de células T (CTCL) |
| EP2751292A4 (en) | 2011-09-01 | 2015-05-20 | Allegro Diagnostics Corp | METHOD AND COMPOSITIONS FOR DETECTING CANCER BASED ON MIRNA EXPRESSION PROFILES |
| RU2648950C2 (ru) | 2011-10-03 | 2018-04-02 | Модерна Терапьютикс, Инк. | Модифицированные нуклеозиды, нуклеотиды и нуклеиновые кислоты и их применение |
| WO2013066678A1 (en) | 2011-10-26 | 2013-05-10 | Georgetown University | Microrna expression profiling of thyroid cancer |
| TR201111743A2 (tr) | 2011-11-28 | 2012-04-24 | Nesl�Han G�Rsoy Reyhan | Kanser tedavisinde kullanılmak üzere yağ bazlı nanotaşıyıcı sistemler. |
| WO2013086502A1 (en) | 2011-12-09 | 2013-06-13 | President And Fellows Of Harvard College | Organ chips and uses thereof |
| US9725687B2 (en) | 2011-12-09 | 2017-08-08 | President And Fellows Of Harvard College | Integrated human organ-on-chip microphysiological systems |
| AU2012352180A1 (en) | 2011-12-16 | 2014-07-31 | Moderna Therapeutics, Inc. | Modified nucleoside, nucleotide, and nucleic acid compositions |
| WO2013103659A1 (en) | 2012-01-04 | 2013-07-11 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Stabilizing rna by incorporating chain-terminating nucleosides at the 3'-terminus |
| US20150064255A1 (en) | 2012-02-22 | 2015-03-05 | Northwestern University | Nanostructures for treating cancers and other conditions |
| WO2013129935A1 (en) | 2012-02-27 | 2013-09-06 | Epitarget As | Use of a particulate immunomodulator in cancer therapy |
| WO2013129936A1 (en) | 2012-02-27 | 2013-09-06 | Epitarget As | Use of an antibody and a particulate immunomodulator in therapy |
| US20130236504A1 (en) | 2012-03-06 | 2013-09-12 | Medical University Of South Carolina | Delivery System for Enhancing Drug Efficacy |
| AU2013243949A1 (en) * | 2012-04-02 | 2014-10-30 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of biologics and proteins associated with human disease |
| WO2013151663A1 (en) * | 2012-04-02 | 2013-10-10 | modeRNA Therapeutics | Modified polynucleotides for the production of membrane proteins |
| HRP20220607T1 (hr) | 2012-11-26 | 2022-06-24 | Modernatx, Inc. | Terminalno modificirana rna |
| EP2946014A2 (en) | 2013-01-17 | 2015-11-25 | Moderna Therapeutics, Inc. | Signal-sensor polynucleotides for the alteration of cellular phenotypes |
| WO2015007871A2 (en) | 2013-07-17 | 2015-01-22 | Ospedale San Raffaele S.R.L. | Micrornas and autoimmune-immune mediated inflammatory disease |
| EP3052106A4 (en) | 2013-09-30 | 2017-07-19 | ModernaTX, Inc. | Polynucleotides encoding immune modulating polypeptides |
| AU2015289573A1 (en) | 2014-07-17 | 2017-02-02 | Modernatx, Inc | Terminal modifications of polynucleotides |
| EP3461904A1 (en) | 2014-11-10 | 2019-04-03 | ModernaTX, Inc. | Alternative nucleic acid molecules containing reduced uracil content and uses thereof |
| SG10201907164SA (en) | 2015-04-22 | 2019-09-27 | Curevac Ag | Rna containing composition for treatment of tumor diseases |
| HRP20220525T1 (hr) | 2015-12-23 | 2022-05-27 | Modernatx, Inc. | Postupci uporabe polinukleotida koji kodiraju ligand ox40 |
-
2013
- 2013-09-30 EP EP13779972.2A patent/EP2946014A2/en not_active Withdrawn
- 2013-09-30 AU AU2013374345A patent/AU2013374345A1/en not_active Abandoned
- 2013-09-30 WO PCT/US2013/062531 patent/WO2014113089A2/en not_active Ceased
- 2013-09-30 HK HK16105211.4A patent/HK1217215A1/zh unknown
- 2013-09-30 EP EP18179340.7A patent/EP3434774A1/en not_active Withdrawn
- 2013-09-30 JP JP2015553717A patent/JP2016504050A/ja active Pending
- 2013-09-30 US US14/041,011 patent/US20140200261A1/en not_active Abandoned
- 2013-09-30 CA CA2897941A patent/CA2897941A1/en not_active Abandoned
- 2013-12-20 US US14/135,876 patent/US20140206852A1/en not_active Abandoned
-
2017
- 2017-02-01 JP JP2017016882A patent/JP2017113010A/ja active Pending
- 2017-08-24 AU AU2017219054A patent/AU2017219054B2/en not_active Ceased
-
2018
- 2018-07-16 US US16/036,170 patent/US20190185529A1/en not_active Abandoned
- 2018-08-03 JP JP2018146351A patent/JP6726711B2/ja active Active
-
2021
- 2021-01-29 US US17/162,061 patent/US11708396B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| EP3434774A1 (en) | 2019-01-30 |
| JP2018183181A (ja) | 2018-11-22 |
| AU2017219054B2 (en) | 2019-09-26 |
| AU2013374345A1 (en) | 2015-08-06 |
| US20140200261A1 (en) | 2014-07-17 |
| US20190185529A1 (en) | 2019-06-20 |
| US11708396B2 (en) | 2023-07-25 |
| US20230013773A1 (en) | 2023-01-19 |
| HK1217215A1 (zh) | 2016-12-30 |
| EP2946014A2 (en) | 2015-11-25 |
| JP2016504050A (ja) | 2016-02-12 |
| WO2014113089A3 (en) | 2014-09-12 |
| WO2014113089A2 (en) | 2014-07-24 |
| US20140206852A1 (en) | 2014-07-24 |
| AU2017219054A1 (en) | 2017-09-14 |
| JP2017113010A (ja) | 2017-06-29 |
| JP6726711B2 (ja) | 2020-07-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20250170228A1 (en) | Terminally modified rna | |
| US11708396B2 (en) | Signal-sensor polynucleotides for the alteration of cellular phenotypes | |
| EP3019619B1 (en) | Compositions comprising synthetic polynucleotides encoding crispr related proteins and synthetic sgrnas and methods of use | |
| US20170252461A1 (en) | Heterologous untranslated regions for mrna | |
| US20170204152A1 (en) | Chimeric polynucleotides | |
| EP3169335A2 (en) | Circular polynucleotides | |
| EP3169783A2 (en) | Terminal modifications of polynucleotides | |
| HK40080438A (en) | Terminally modified rna | |
| HK40070836A (en) | Compositions comprising synthetic polynucleotides encoding crispr related proteins and synthetic sgrnas and methods of use | |
| HK40005169A (en) | Signal-sensor polynucleotides for the alteration of cellular phenotypes | |
| HK1214515B (en) | Terminally modified rna | |
| HK1224700B (en) | Compositions comprising synthetic polynucleotides encoding crispr related proteins and synthetic sgrnas and methods of use |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20150710 |
|
| EEER | Examination request |
Effective date: 20150710 |
|
| EEER | Examination request |
Effective date: 20150710 |
|
| EEER | Examination request |
Effective date: 20150710 |
|
| EEER | Examination request |
Effective date: 20150710 |
|
| FZDE | Discontinued |
Effective date: 20240220 |