CN112739353A - Mir-92a或mir-145在治疗安格曼综合征中的用途 - Google Patents
Mir-92a或mir-145在治疗安格曼综合征中的用途 Download PDFInfo
- Publication number
- CN112739353A CN112739353A CN201980040006.2A CN201980040006A CN112739353A CN 112739353 A CN112739353 A CN 112739353A CN 201980040006 A CN201980040006 A CN 201980040006A CN 112739353 A CN112739353 A CN 112739353A
- Authority
- CN
- China
- Prior art keywords
- microrna
- vector
- promoter
- patient
- precursor
- 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.)
- Pending
Links
- 208000011580 syndromic disease Diseases 0.000 title claims abstract description 48
- 108091028684 Mir-145 Proteins 0.000 title claims abstract description 41
- 108091034121 miR-92a stem-loop Proteins 0.000 title claims abstract description 40
- 108091041519 miR-92a-3 stem-loop Proteins 0.000 title claims abstract description 40
- 230000014509 gene expression Effects 0.000 claims abstract description 25
- 238000000034 method Methods 0.000 claims description 68
- 239000013598 vector Substances 0.000 claims description 60
- 239000002243 precursor Substances 0.000 claims description 40
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 34
- 208000024891 symptom Diseases 0.000 claims description 33
- 239000000203 mixture Substances 0.000 claims description 29
- 210000004556 brain Anatomy 0.000 claims description 25
- 238000012384 transportation and delivery Methods 0.000 claims description 24
- 208000035475 disorder Diseases 0.000 claims description 23
- 150000007523 nucleic acids Chemical class 0.000 claims description 23
- 239000008194 pharmaceutical composition Substances 0.000 claims description 23
- 108020004707 nucleic acids Proteins 0.000 claims description 22
- 102000039446 nucleic acids Human genes 0.000 claims description 22
- 241000702421 Dependoparvovirus Species 0.000 claims description 9
- 241000713666 Lentivirus Species 0.000 claims description 8
- 230000008488 polyadenylation Effects 0.000 claims description 8
- 230000001105 regulatory effect Effects 0.000 claims description 8
- 241000702423 Adeno-associated virus - 2 Species 0.000 claims description 7
- 238000002604 ultrasonography Methods 0.000 claims description 7
- 230000008499 blood brain barrier function Effects 0.000 claims description 6
- 210000001218 blood-brain barrier Anatomy 0.000 claims description 5
- 230000001124 posttranscriptional effect Effects 0.000 claims description 5
- 241001164825 Adeno-associated virus - 8 Species 0.000 claims description 4
- 206010010904 Convulsion Diseases 0.000 claims description 4
- 241000283923 Marmota monax Species 0.000 claims description 4
- 108010006025 bovine growth hormone Proteins 0.000 claims description 4
- 230000035699 permeability Effects 0.000 claims description 4
- 230000000699 topical effect Effects 0.000 claims description 4
- 241001655883 Adeno-associated virus - 1 Species 0.000 claims description 3
- 241000580270 Adeno-associated virus - 4 Species 0.000 claims description 3
- 241001634120 Adeno-associated virus - 5 Species 0.000 claims description 3
- 108010003721 Calcium-Calmodulin-Dependent Protein Kinase Type 2 Proteins 0.000 claims description 3
- 206010012559 Developmental delay Diseases 0.000 claims description 3
- 108010065372 Dynorphins Proteins 0.000 claims description 3
- 101000575685 Homo sapiens Synembryn-B Proteins 0.000 claims description 3
- 102100024622 Proenkephalin-B Human genes 0.000 claims description 3
- 102100026014 Synembryn-B Human genes 0.000 claims description 3
- 230000006735 deficit Effects 0.000 claims description 3
- 208000004141 microcephaly Diseases 0.000 claims description 3
- 230000002829 reductive effect Effects 0.000 claims description 3
- 208000005622 Gait Ataxia Diseases 0.000 claims description 2
- 206010044565 Tremor Diseases 0.000 claims description 2
- 239000002502 liposome Substances 0.000 claims description 2
- 230000003340 mental effect Effects 0.000 claims description 2
- 241001164823 Adeno-associated virus - 7 Species 0.000 claims 2
- 102000004657 Calcium-Calmodulin-Dependent Protein Kinase Type 2 Human genes 0.000 claims 2
- 101000821100 Homo sapiens Synapsin-1 Proteins 0.000 claims 2
- 239000013603 viral vector Substances 0.000 claims 2
- 206010001497 Agitation Diseases 0.000 claims 1
- 230000001668 ameliorated effect Effects 0.000 claims 1
- 230000001404 mediated effect Effects 0.000 claims 1
- 108091070501 miRNA Proteins 0.000 abstract description 68
- 238000011282 treatment Methods 0.000 abstract description 31
- 108090000623 proteins and genes Proteins 0.000 abstract description 19
- 239000013604 expression vector Substances 0.000 abstract description 18
- 108700011259 MicroRNAs Proteins 0.000 abstract description 10
- 230000000694 effects Effects 0.000 abstract description 8
- 239000013607 AAV vector Substances 0.000 abstract description 6
- -1 for example Substances 0.000 abstract description 2
- 210000004027 cell Anatomy 0.000 description 28
- 239000003981 vehicle Substances 0.000 description 23
- 239000002679 microRNA Substances 0.000 description 18
- 230000006872 improvement Effects 0.000 description 15
- 238000007911 parenteral administration Methods 0.000 description 14
- 201000010099 disease Diseases 0.000 description 11
- 150000001875 compounds Chemical class 0.000 description 10
- 241000282414 Homo sapiens Species 0.000 description 9
- 210000003169 central nervous system Anatomy 0.000 description 9
- 239000000546 pharmaceutical excipient Substances 0.000 description 9
- 239000013543 active substance Substances 0.000 description 8
- 102100030434 Ubiquitin-protein ligase E3A Human genes 0.000 description 7
- 101710188886 Ubiquitin-protein ligase E3A Proteins 0.000 description 7
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 6
- 101100155061 Homo sapiens UBE3A gene Proteins 0.000 description 6
- 101150045356 UBE3A gene Proteins 0.000 description 6
- 230000037396 body weight Effects 0.000 description 6
- 230000008774 maternal effect Effects 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 241000701022 Cytomegalovirus Species 0.000 description 5
- 230000000144 pharmacologic effect Effects 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- 230000003612 virological effect Effects 0.000 description 5
- 108091026890 Coding region Proteins 0.000 description 4
- 241000700605 Viruses Species 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 210000000234 capsid Anatomy 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 210000002569 neuron Anatomy 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 239000013609 scAAV vector Substances 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 3
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 3
- 102000053171 Glial Fibrillary Acidic Human genes 0.000 description 3
- 101710193519 Glial fibrillary acidic protein Proteins 0.000 description 3
- 230000006399 behavior Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 210000005013 brain tissue Anatomy 0.000 description 3
- 210000000349 chromosome Anatomy 0.000 description 3
- 230000007547 defect Effects 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 239000003623 enhancer Substances 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 210000005046 glial fibrillary acidic protein Anatomy 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 238000007912 intraperitoneal administration Methods 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 230000001537 neural effect Effects 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 210000003625 skull Anatomy 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 230000002618 waking effect Effects 0.000 description 3
- 102000053602 DNA Human genes 0.000 description 2
- 101000834253 Gallus gallus Actin, cytoplasmic 1 Proteins 0.000 description 2
- 108700007698 Genetic Terminator Regions Proteins 0.000 description 2
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 2
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 2
- 108091005904 Hemoglobin subunit beta Proteins 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 102000011755 Phosphoglycerate Kinase Human genes 0.000 description 2
- 108020005067 RNA Splice Sites Proteins 0.000 description 2
- 101001099217 Thermotoga maritima (strain ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8) Triosephosphate isomerase Proteins 0.000 description 2
- 108010022394 Threonine synthase Proteins 0.000 description 2
- 108700019146 Transgenes Proteins 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 230000003542 behavioural effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 210000004720 cerebrum Anatomy 0.000 description 2
- 102000004419 dihydrofolate reductase Human genes 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000009395 genetic defect Effects 0.000 description 2
- 239000005090 green fluorescent protein Substances 0.000 description 2
- 210000003016 hypothalamus Anatomy 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 210000001577 neostriatum Anatomy 0.000 description 2
- 230000008775 paternal effect Effects 0.000 description 2
- 239000000902 placebo Substances 0.000 description 2
- 229940068196 placebo Drugs 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 210000000278 spinal cord Anatomy 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 210000001103 thalamus Anatomy 0.000 description 2
- 238000010361 transduction Methods 0.000 description 2
- 230000026683 transduction Effects 0.000 description 2
- 241001430294 unidentified retrovirus Species 0.000 description 2
- YMHOBZXQZVXHBM-UHFFFAOYSA-N 2,5-dimethoxy-4-bromophenethylamine Chemical compound COC1=CC(CCN)=C(OC)C=C1Br YMHOBZXQZVXHBM-UHFFFAOYSA-N 0.000 description 1
- KISWVXRQTGLFGD-UHFFFAOYSA-N 2-[[2-[[6-amino-2-[[2-[[2-[[5-amino-2-[[2-[[1-[2-[[6-amino-2-[(2,5-diamino-5-oxopentanoyl)amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)p Chemical compound C1CCN(C(=O)C(CCCN=C(N)N)NC(=O)C(CCCCN)NC(=O)C(N)CCC(N)=O)C1C(=O)NC(CO)C(=O)NC(CCC(N)=O)C(=O)NC(CCCN=C(N)N)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 KISWVXRQTGLFGD-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 208000009575 Angelman syndrome Diseases 0.000 description 1
- 239000004072 C09CA03 - Valsartan Substances 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 108091005960 Citrine Proteins 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 102100031780 Endonuclease Human genes 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 241000282324 Felis Species 0.000 description 1
- 206010064571 Gene mutation Diseases 0.000 description 1
- 101100412102 Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd) rec2 gene Proteins 0.000 description 1
- 101100356020 Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd) recA gene Proteins 0.000 description 1
- 102100021519 Hemoglobin subunit beta Human genes 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 1
- 102100021244 Integral membrane protein GPR180 Human genes 0.000 description 1
- 201000006347 Intellectual Disability Diseases 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- URLZCHNOLZSCCA-VABKMULXSA-N Leu-enkephalin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)CNC(=O)CNC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=CC=C1 URLZCHNOLZSCCA-VABKMULXSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 101100155062 Mus musculus Ube3a gene Proteins 0.000 description 1
- 102000047918 Myelin Basic Human genes 0.000 description 1
- 101710107068 Myelin basic protein Proteins 0.000 description 1
- 208000029726 Neurodevelopmental disease Diseases 0.000 description 1
- 108010088373 Neurofilament Proteins Proteins 0.000 description 1
- 108091005461 Nucleic proteins Proteins 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241000125945 Protoparvovirus Species 0.000 description 1
- 108091030071 RNAI Proteins 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- 108020003224 Small Nucleolar RNA Proteins 0.000 description 1
- 102000042773 Small Nucleolar RNA Human genes 0.000 description 1
- 108091000117 Tyrosine 3-Monooxygenase Proteins 0.000 description 1
- 102000048218 Tyrosine 3-monooxygenases Human genes 0.000 description 1
- 108091060203 Ube3a-ATS Proteins 0.000 description 1
- 241000545067 Venus Species 0.000 description 1
- 108700005077 Viral Genes Proteins 0.000 description 1
- 241001492404 Woodchuck hepatitis virus Species 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 238000011374 additional therapy Methods 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 210000004727 amygdala Anatomy 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 210000004507 artificial chromosome Anatomy 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 210000004227 basal ganglia Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 210000004958 brain cell Anatomy 0.000 description 1
- 210000000133 brain stem Anatomy 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 210000001638 cerebellum Anatomy 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 239000011035 citrine Substances 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000003759 clinical diagnosis Methods 0.000 description 1
- 239000008199 coating composition Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 238000007428 craniotomy Methods 0.000 description 1
- 230000007711 cytoplasmic localization Effects 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000001973 epigenetic effect Effects 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 210000001652 frontal lobe Anatomy 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000003371 gabaergic effect Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000009368 gene silencing by RNA Effects 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 235000021474 generally recognized As safe (food) Nutrition 0.000 description 1
- 235000021473 generally recognized as safe (food ingredients) Nutrition 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 230000008303 genetic mechanism Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 230000001660 hyperkinetic effect Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 210000003715 limbic system Anatomy 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000009593 lumbar puncture Methods 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 210000001767 medulla oblongata Anatomy 0.000 description 1
- 210000001259 mesencephalon Anatomy 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 210000000478 neocortex Anatomy 0.000 description 1
- 230000007372 neural signaling Effects 0.000 description 1
- 230000001123 neurodevelopmental effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 230000030648 nucleus localization Effects 0.000 description 1
- 210000000869 occipital lobe Anatomy 0.000 description 1
- 230000001936 parietal effect Effects 0.000 description 1
- 210000001152 parietal lobe Anatomy 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000001817 pituitary effect Effects 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 108091007428 primary miRNA Proteins 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 210000004129 prosencephalon Anatomy 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 208000022925 sleep disturbance Diseases 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000008137 solubility enhancer Substances 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 230000010473 stable expression Effects 0.000 description 1
- 238000011301 standard therapy Methods 0.000 description 1
- 210000003523 substantia nigra Anatomy 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000012385 systemic delivery Methods 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- 210000001587 telencephalon Anatomy 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 210000003478 temporal lobe Anatomy 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000005026 transcription initiation Effects 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- FTKOCAZZFUDHDQ-OXLBYMFNSA-N α-cam Chemical compound C([C@@H](N(CC1)C)C23C=C[C@@]4([C@H](C3)CN(CCCl)CCCl)OC)C3=CC=C(O)C5=C3[C@@]21[C@H]4O5 FTKOCAZZFUDHDQ-OXLBYMFNSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0047—Sonopheresis, i.e. ultrasonically-enhanced transdermal delivery, electroporation of a pharmacologically active agent
-
- 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
- A61K48/0075—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 delivery route, e.g. oral, subcutaneous
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- 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
-
- 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
- C12N2320/00—Applications; Uses
- C12N2320/30—Special therapeutic applications
- C12N2320/32—Special delivery means, e.g. tissue-specific
-
- 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
- C12N2330/00—Production
- C12N2330/50—Biochemical production, i.e. in a transformed host cell
- C12N2330/51—Specially adapted vectors
-
- 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
- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/15011—Lentivirus, not HIV, e.g. FIV, SIV
- C12N2740/15041—Use of virus, viral particle or viral elements as a vector
- C12N2740/15043—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
-
- 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
- C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
- C12N2750/00011—Details
- C12N2750/14011—Parvoviridae
- C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
- C12N2750/14141—Use of virus, viral particle or viral elements as a vector
- C12N2750/14143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Dermatology (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201862684774P | 2018-06-14 | 2018-06-14 | |
| US62/684,774 | 2018-06-14 | ||
| PCT/US2019/037174 WO2019241624A1 (en) | 2018-06-14 | 2019-06-14 | Use of mir-92a or mir-145 in the treatment of angelman syndrome |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112739353A true CN112739353A (zh) | 2021-04-30 |
Family
ID=68839583
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201980040006.2A Pending CN112739353A (zh) | 2018-06-14 | 2019-06-14 | Mir-92a或mir-145在治疗安格曼综合征中的用途 |
Country Status (10)
| Country | Link |
|---|---|
| US (2) | US10704048B2 (https=) |
| EP (1) | EP3793567A4 (https=) |
| JP (1) | JP2021527087A (https=) |
| KR (1) | KR20210040358A (https=) |
| CN (1) | CN112739353A (https=) |
| AU (1) | AU2019285298A1 (https=) |
| CA (1) | CA3103267A1 (https=) |
| IL (1) | IL279391A (https=) |
| MX (1) | MX2020013667A (https=) |
| WO (1) | WO2019241624A1 (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111163811A (zh) * | 2017-08-25 | 2020-05-15 | 奥维德医疗公司 | 重组腺相关载体 |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20210040358A (ko) | 2018-06-14 | 2021-04-13 | 오비드 테라퓨틱스 인크. | 안젤만 증후군의 치료에서 mir-92a 또는 mir-145의 사용 |
| WO2020227604A1 (en) * | 2019-05-08 | 2020-11-12 | Nova Southeastern University | Regulation of nucleotide excision repair (ner) by microrna for treatment of breast cancer |
| IL303239A (en) * | 2020-12-01 | 2023-07-01 | Univ Pennsylvania | Compositions and their uses for the treatment of Engelmann syndrome |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102676516A (zh) * | 2011-03-17 | 2012-09-19 | 中国医学科学院肿瘤研究所 | microRNA 145的新用途 |
| US20150267193A1 (en) * | 2011-10-14 | 2015-09-24 | Ramanuj Dasgupta | MicroRNAs and Methods of Using Same |
| CN107530451A (zh) * | 2015-05-07 | 2018-01-02 | 南佛罗里达大学 | 用于天使人综合征的基因治疗方法的修饰的ube3a基因 |
| CN108024997A (zh) * | 2015-07-17 | 2018-05-11 | 奥维德医疗公司 | 用加波沙朵治疗发育障碍的方法 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5752515A (en) | 1996-08-21 | 1998-05-19 | Brigham & Women's Hospital | Methods and apparatus for image-guided ultrasound delivery of compounds through the blood-brain barrier |
| WO2006128245A1 (en) | 2005-06-03 | 2006-12-07 | Southern Adelaide Health Service-Flinders Medical Centre | Targeting cells with altered microrna expression |
| EP1937151A4 (en) | 2005-09-19 | 2011-07-06 | Univ Columbia | Systems and methods for opening of the blood-brain barrier of a subject using ultrasound |
| EA201492116A1 (ru) * | 2012-05-16 | 2015-05-29 | Рана Терапьютикс, Инк. | Композиции и способы для модулирования экспрессии mecp2 |
| WO2014004572A2 (en) | 2012-06-25 | 2014-01-03 | Isis Pharmaceuticals, Inc. | Modulation of ube3a-ats expression |
| US20190298843A1 (en) * | 2015-05-11 | 2019-10-03 | Purdue Research Foundation | Ligand ionophore conjugates |
| KR20210040358A (ko) | 2018-06-14 | 2021-04-13 | 오비드 테라퓨틱스 인크. | 안젤만 증후군의 치료에서 mir-92a 또는 mir-145의 사용 |
-
2019
- 2019-06-14 KR KR1020217001109A patent/KR20210040358A/ko not_active Withdrawn
- 2019-06-14 JP JP2020568984A patent/JP2021527087A/ja not_active Withdrawn
- 2019-06-14 WO PCT/US2019/037174 patent/WO2019241624A1/en not_active Ceased
- 2019-06-14 US US16/441,391 patent/US10704048B2/en active Active
- 2019-06-14 MX MX2020013667A patent/MX2020013667A/es unknown
- 2019-06-14 CN CN201980040006.2A patent/CN112739353A/zh active Pending
- 2019-06-14 EP EP19819943.2A patent/EP3793567A4/en not_active Withdrawn
- 2019-06-14 CA CA3103267A patent/CA3103267A1/en active Pending
- 2019-06-14 AU AU2019285298A patent/AU2019285298A1/en not_active Abandoned
-
2020
- 2020-07-07 US US16/922,273 patent/US11130952B2/en active Active
- 2020-12-13 IL IL279391A patent/IL279391A/en unknown
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102676516A (zh) * | 2011-03-17 | 2012-09-19 | 中国医学科学院肿瘤研究所 | microRNA 145的新用途 |
| US20150267193A1 (en) * | 2011-10-14 | 2015-09-24 | Ramanuj Dasgupta | MicroRNAs and Methods of Using Same |
| CN107530451A (zh) * | 2015-05-07 | 2018-01-02 | 南佛罗里达大学 | 用于天使人综合征的基因治疗方法的修饰的ube3a基因 |
| CN108024997A (zh) * | 2015-07-17 | 2018-05-11 | 奥维德医疗公司 | 用加波沙朵治疗发育障碍的方法 |
Non-Patent Citations (1)
| Title |
|---|
| LINYAN MENG等: "Towards a therapy for Angelman syndrome by targeting a long non-coding RNA", NATURE, vol. 518, no. 7539, pages 409 - 412, XP055556384, DOI: 10.1038/nature13975 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111163811A (zh) * | 2017-08-25 | 2020-05-15 | 奥维德医疗公司 | 重组腺相关载体 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2019241624A1 (en) | 2019-12-19 |
| JP2021527087A (ja) | 2021-10-11 |
| EP3793567A1 (en) | 2021-03-24 |
| MX2020013667A (es) | 2021-03-02 |
| US11130952B2 (en) | 2021-09-28 |
| CA3103267A1 (en) | 2019-12-19 |
| KR20210040358A (ko) | 2021-04-13 |
| EP3793567A4 (en) | 2021-08-11 |
| US20200332294A1 (en) | 2020-10-22 |
| IL279391A (en) | 2021-01-31 |
| US20190382761A1 (en) | 2019-12-19 |
| US10704048B2 (en) | 2020-07-07 |
| AU2019285298A1 (en) | 2021-01-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11903985B2 (en) | Gene therapies for lysosomal disorders | |
| US12516298B2 (en) | Gene therapies for lysosomal disorders | |
| US11130952B2 (en) | Use of MIR-92A or MIR-145 in the treatment of Angelman syndrome | |
| JP2021521152A (ja) | 抑制性ニューロンにおける電位開口型ナトリウムチャネルのレスキュー | |
| US20230346979A1 (en) | Gene therapies for neurodegenerative disorders | |
| WO2023240236A1 (en) | Compositions and methods for the treatment of spinal muscular atrophy related disorders | |
| CA2967468A1 (en) | Gene therapy for juvenile batten disease | |
| CN112451669A (zh) | Ptbp1抑制剂在预防和/或治疗功能性神经元死亡相关的神经系统疾病中的应用 | |
| US20230310654A1 (en) | Gene therapies for lysosomal disorders | |
| US20260117229A1 (en) | Slc2a1 lncrna as a biologic and related treatments and methods | |
| AU2025275257A1 (en) | Expression vector for cholesterol 24-hydrolase in therapy of amyotrophic lateral sclerosis | |
| EP4370679A2 (en) | Enhancers driving expression in motor neurons | |
| US11761006B2 (en) | Use of MIR101 or MIR128 in the treatment of seizure disorders | |
| EP4437116A1 (en) | Compositions and methods for cell-specific expression of target genes | |
| WO2026039331A1 (en) | Viral therapy for the treatment of mef2c haploinsufficiency syndrome | |
| WO2025212993A1 (en) | Materials and methods for trangene expression in neural cells | |
| WO2025038955A9 (en) | Systems and methods for improving safety of split intein aav mediated gene therapy |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20210430 |
|
| WD01 | Invention patent application deemed withdrawn after publication |