CN107007842A - 神经代谢疾病的基因治疗 - Google Patents
神经代谢疾病的基因治疗 Download PDFInfo
- Publication number
- CN107007842A CN107007842A CN201611031204.7A CN201611031204A CN107007842A CN 107007842 A CN107007842 A CN 107007842A CN 201611031204 A CN201611031204 A CN 201611031204A CN 107007842 A CN107007842 A CN 107007842A
- Authority
- CN
- China
- Prior art keywords
- aav
- site
- aav2
- mouse
- asm
- 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
- 208000030159 metabolic disease Diseases 0.000 title claims abstract description 20
- 210000005036 nerve Anatomy 0.000 title abstract description 34
- 238000001415 gene therapy Methods 0.000 title abstract description 18
- 238000000034 method Methods 0.000 claims abstract description 101
- 210000003169 central nervous system Anatomy 0.000 claims abstract description 51
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 50
- 201000010099 disease Diseases 0.000 claims abstract description 49
- 239000000969 carrier Substances 0.000 claims abstract description 46
- 239000000203 mixture Substances 0.000 claims abstract description 29
- 208000015439 Lysosomal storage disease Diseases 0.000 claims abstract description 25
- 210000004556 brain Anatomy 0.000 claims description 99
- 241000702423 Adeno-associated virus - 2 Species 0.000 claims description 81
- 210000004027 cell Anatomy 0.000 claims description 68
- 108010061312 Sphingomyelin Phosphodiesterase Proteins 0.000 claims description 66
- 102000010126 acid sphingomyelin phosphodiesterase activity proteins Human genes 0.000 claims description 64
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 54
- 210000001320 hippocampus Anatomy 0.000 claims description 54
- 230000014509 gene expression Effects 0.000 claims description 44
- 210000001638 cerebellum Anatomy 0.000 claims description 34
- 210000000278 spinal cord Anatomy 0.000 claims description 27
- 238000010361 transduction Methods 0.000 claims description 25
- 230000026683 transduction Effects 0.000 claims description 25
- 230000002490 cerebral effect Effects 0.000 claims description 24
- 239000013598 vector Substances 0.000 claims description 18
- 108090000028 Neprilysin Proteins 0.000 claims description 17
- 102000004190 Enzymes Human genes 0.000 claims description 16
- 108090000790 Enzymes Proteins 0.000 claims description 16
- 102000003729 Neprilysin Human genes 0.000 claims description 16
- 102000004157 Hydrolases Human genes 0.000 claims description 14
- 108090000604 Hydrolases Proteins 0.000 claims description 14
- 241000124008 Mammalia Species 0.000 claims description 14
- 230000000975 bioactive effect Effects 0.000 claims description 14
- 210000001353 entorhinal cortex Anatomy 0.000 claims description 14
- 230000002132 lysosomal effect Effects 0.000 claims description 14
- 210000003712 lysosome Anatomy 0.000 claims description 13
- 210000000133 brain stem Anatomy 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 12
- 230000001868 lysosomic effect Effects 0.000 claims description 12
- 241001655883 Adeno-associated virus - 1 Species 0.000 claims description 11
- 241000702421 Dependoparvovirus Species 0.000 claims description 11
- 101710151579 Zinc metalloproteinase Proteins 0.000 claims description 11
- 210000000234 capsid Anatomy 0.000 claims description 9
- 210000001947 dentate gyrus Anatomy 0.000 claims description 9
- 210000001103 thalamus Anatomy 0.000 claims description 8
- 230000002159 abnormal effect Effects 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 7
- 241001634120 Adeno-associated virus - 5 Species 0.000 claims description 6
- 241001164823 Adeno-associated virus - 7 Species 0.000 claims description 5
- 210000003710 cerebral cortex Anatomy 0.000 claims description 5
- 230000004060 metabolic process Effects 0.000 claims description 5
- 241000202702 Adeno-associated virus - 3 Species 0.000 claims description 4
- 241000580270 Adeno-associated virus - 4 Species 0.000 claims description 4
- 241000972680 Adeno-associated virus - 6 Species 0.000 claims description 4
- 241001164825 Adeno-associated virus - 8 Species 0.000 claims description 4
- 102100021496 Insulin-degrading enzyme Human genes 0.000 claims description 4
- 108090000828 Insulysin Proteins 0.000 claims description 4
- 102100031293 Thimet oligopeptidase Human genes 0.000 claims description 4
- 210000003016 hypothalamus Anatomy 0.000 claims description 4
- 210000001259 mesencephalon Anatomy 0.000 claims description 4
- 108091033319 polynucleotide Proteins 0.000 claims description 4
- 102000040430 polynucleotide Human genes 0.000 claims description 4
- 239000002157 polynucleotide Substances 0.000 claims description 4
- 108010073106 thimet oligopeptidase Proteins 0.000 claims description 4
- 210000001652 frontal lobe Anatomy 0.000 claims description 3
- 210000000869 occipital lobe Anatomy 0.000 claims description 3
- 210000003478 temporal lobe Anatomy 0.000 claims description 3
- 238000013519 translation Methods 0.000 claims description 2
- 230000008335 axon cargo transport Effects 0.000 abstract description 29
- 108700019146 Transgenes Proteins 0.000 abstract description 28
- 230000001225 therapeutic effect Effects 0.000 abstract description 16
- 241000699666 Mus <mouse, genus> Species 0.000 description 129
- 238000002347 injection Methods 0.000 description 90
- 239000007924 injection Substances 0.000 description 90
- 230000007170 pathology Effects 0.000 description 41
- 210000002569 neuron Anatomy 0.000 description 37
- 108090000623 proteins and genes Proteins 0.000 description 37
- 210000000449 purkinje cell Anatomy 0.000 description 27
- 238000011282 treatment Methods 0.000 description 26
- 230000002441 reversible effect Effects 0.000 description 25
- 238000012937 correction Methods 0.000 description 24
- 238000012545 processing Methods 0.000 description 22
- 235000012000 cholesterol Nutrition 0.000 description 21
- 238000004043 dyeing Methods 0.000 description 21
- 239000013603 viral vector Substances 0.000 description 21
- 108010005774 beta-Galactosidase Proteins 0.000 description 20
- 229930183931 Filipin Natural products 0.000 description 19
- 229950000152 filipin Drugs 0.000 description 19
- IMQSIXYSKPIGPD-UHFFFAOYSA-N filipin III Natural products CCCCCC(O)C1C(O)CC(O)CC(O)CC(O)CC(O)CC(O)CC(O)C(C)=CC=CC=CC=CC=CC(O)C(C)OC1=O IMQSIXYSKPIGPD-UHFFFAOYSA-N 0.000 description 19
- 239000005090 green fluorescent protein Substances 0.000 description 19
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 18
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 18
- IMQSIXYSKPIGPD-NKYUYKLDSA-N filipin Chemical compound CCCCC[C@H](O)[C@@H]1[C@@H](O)C[C@@H](O)C[C@@H](O)C[C@@H](O)C[C@@H](O)C[C@@H](O)C[C@H](O)\C(C)=C\C=C\C=C\C=C\C=C\[C@H](O)[C@@H](C)OC1=O IMQSIXYSKPIGPD-NKYUYKLDSA-N 0.000 description 18
- 238000012360 testing method Methods 0.000 description 17
- 102000004169 proteins and genes Human genes 0.000 description 16
- 230000032258 transport Effects 0.000 description 16
- 102000014823 calbindin Human genes 0.000 description 14
- 108060001061 calbindin Proteins 0.000 description 14
- 241000700605 Viruses Species 0.000 description 13
- 108020004999 messenger RNA Proteins 0.000 description 13
- 238000009826 distribution Methods 0.000 description 12
- 210000001176 projection neuron Anatomy 0.000 description 12
- 230000009467 reduction Effects 0.000 description 11
- 241000699670 Mus sp. Species 0.000 description 10
- 230000005540 biological transmission Effects 0.000 description 10
- 239000002245 particle Substances 0.000 description 10
- 210000002845 virion Anatomy 0.000 description 10
- 230000035508 accumulation Effects 0.000 description 9
- 238000009825 accumulation Methods 0.000 description 9
- 230000006870 function Effects 0.000 description 9
- 239000010410 layer Substances 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 9
- 206010051914 Cholesterosis Diseases 0.000 description 8
- 108020004414 DNA Proteins 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 210000005056 cell body Anatomy 0.000 description 8
- 208000015181 infectious disease Diseases 0.000 description 8
- 230000034994 death Effects 0.000 description 7
- 239000002953 phosphate buffered saline Substances 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 6
- 208000015114 central nervous system disease Diseases 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 238000009792 diffusion process Methods 0.000 description 6
- 208000016097 disease of metabolism Diseases 0.000 description 6
- 238000010166 immunofluorescence Methods 0.000 description 6
- 210000002966 serum Anatomy 0.000 description 6
- 238000012546 transfer Methods 0.000 description 6
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 6
- 241000701022 Cytomegalovirus Species 0.000 description 5
- 241000283074 Equus asinus Species 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 230000001054 cortical effect Effects 0.000 description 5
- 238000009396 hybridization Methods 0.000 description 5
- 230000002458 infectious effect Effects 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- 230000004083 survival effect Effects 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 102100026189 Beta-galactosidase Human genes 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- NCEXYHBECQHGNR-UHFFFAOYSA-N chembl421 Chemical compound C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000003384 imaging method Methods 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 230000030214 innervation Effects 0.000 description 4
- 230000033001 locomotion Effects 0.000 description 4
- 210000000274 microglia Anatomy 0.000 description 4
- 230000001537 neural effect Effects 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 210000003625 skull Anatomy 0.000 description 4
- 238000010186 staining Methods 0.000 description 4
- 238000003860 storage Methods 0.000 description 4
- 230000033912 thigmotaxis Effects 0.000 description 4
- OPIFSICVWOWJMJ-AEOCFKNESA-N 5-bromo-4-chloro-3-indolyl beta-D-galactoside Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1OC1=CNC2=CC=C(Br)C(Cl)=C12 OPIFSICVWOWJMJ-AEOCFKNESA-N 0.000 description 3
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 3
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 3
- 206010002091 Anaesthesia Diseases 0.000 description 3
- 102000053602 DNA Human genes 0.000 description 3
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 3
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 208000014060 Niemann-Pick disease Diseases 0.000 description 3
- 108091029810 SaRNA Proteins 0.000 description 3
- 241000936757 Streptomyces filipinensis Species 0.000 description 3
- 230000037005 anaesthesia Effects 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 230000002146 bilateral effect Effects 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 210000003591 cerebellar nuclei Anatomy 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000000834 fixative Substances 0.000 description 3
- 238000012744 immunostaining Methods 0.000 description 3
- 238000007901 in situ hybridization Methods 0.000 description 3
- 229960002725 isoflurane Drugs 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 230000002503 metabolic effect Effects 0.000 description 3
- 239000002052 molecular layer Substances 0.000 description 3
- 230000007659 motor function Effects 0.000 description 3
- 210000002161 motor neuron Anatomy 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 229940078677 sarna Drugs 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- 230000009261 transgenic effect Effects 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- LRYZPFWEZHSTHD-HEFFAWAOSA-O 2-[[(e,2s,3r)-2-formamido-3-hydroxyoctadec-4-enoxy]-hydroxyphosphoryl]oxyethyl-trimethylazanium Chemical class CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](NC=O)COP(O)(=O)OCC[N+](C)(C)C LRYZPFWEZHSTHD-HEFFAWAOSA-O 0.000 description 2
- HVYWMOMLDIMFJA-UHFFFAOYSA-N 3-cholesterol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)CCCC(C)C)C1(C)CC2 HVYWMOMLDIMFJA-UHFFFAOYSA-N 0.000 description 2
- TWQHGBJNKVFWIU-UHFFFAOYSA-N 8-[4-(4-quinolin-2-ylpiperazin-1-yl)butyl]-8-azaspiro[4.5]decane-7,9-dione Chemical compound C1C(=O)N(CCCCN2CCN(CC2)C=2N=C3C=CC=CC3=CC=2)C(=O)CC21CCCC2 TWQHGBJNKVFWIU-UHFFFAOYSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 2
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 2
- 208000026350 Inborn Genetic disease Diseases 0.000 description 2
- 102100021244 Integral membrane protein GPR180 Human genes 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- 102000012288 Phosphopyruvate Hydratase Human genes 0.000 description 2
- 108010022181 Phosphopyruvate Hydratase Proteins 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 108700008625 Reporter Genes Proteins 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 230000001133 acceleration Effects 0.000 description 2
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 2
- 210000003484 anatomy Anatomy 0.000 description 2
- 210000003050 axon Anatomy 0.000 description 2
- 230000003376 axonal effect Effects 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 230000008499 blood brain barrier function Effects 0.000 description 2
- 230000036770 blood supply Effects 0.000 description 2
- 210000001218 blood-brain barrier Anatomy 0.000 description 2
- 108010006025 bovine growth hormone Proteins 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- AIYUHDOJVYHVIT-UHFFFAOYSA-M caesium chloride Chemical compound [Cl-].[Cs+] AIYUHDOJVYHVIT-UHFFFAOYSA-M 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 210000003198 cerebellar cortex Anatomy 0.000 description 2
- 210000004720 cerebrum Anatomy 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000001186 cumulative effect Effects 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 210000002451 diencephalon Anatomy 0.000 description 2
- 239000013024 dilution buffer Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 235000013601 eggs Nutrition 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000000799 fluorescence microscopy Methods 0.000 description 2
- MURGITYSBWUQTI-UHFFFAOYSA-N fluorescin Chemical compound OC(=O)C1=CC=CC=C1C1C2=CC=C(O)C=C2OC2=CC(O)=CC=C21 MURGITYSBWUQTI-UHFFFAOYSA-N 0.000 description 2
- -1 for example Proteins 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 239000003205 fragrance Substances 0.000 description 2
- 230000009395 genetic defect Effects 0.000 description 2
- 208000016361 genetic disease Diseases 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 238000011813 knockout mouse model Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 210000000653 nervous system Anatomy 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 210000000956 olfactory bulb Anatomy 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 230000010412 perfusion Effects 0.000 description 2
- YNPNZTXNASCQKK-UHFFFAOYSA-N phenanthrene Chemical compound C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 239000002356 single layer Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 230000003977 synaptic function Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- UAIUNKRWKOVEES-UHFFFAOYSA-N 3,3',5,5'-tetramethylbenzidine Chemical compound CC1=C(N)C(C)=CC(C=2C=C(C)C(N)=C(C)C=2)=C1 UAIUNKRWKOVEES-UHFFFAOYSA-N 0.000 description 1
- 239000013607 AAV vector Substances 0.000 description 1
- 102100022900 Actin, cytoplasmic 1 Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 238000010173 Alzheimer-disease mouse model Methods 0.000 description 1
- 244000144725 Amygdalus communis Species 0.000 description 1
- 208000037259 Amyloid Plaque Diseases 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 230000007134 Aβ oligomerisation Effects 0.000 description 1
- 102100026031 Beta-glucuronidase Human genes 0.000 description 1
- 102100022548 Beta-hexosaminidase subunit alpha Human genes 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 241000557626 Corvus corax Species 0.000 description 1
- NBSCHQHZLSJFNQ-QTVWNMPRSA-N D-Mannose-6-phosphate Chemical compound OC1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H](O)[C@@H]1O NBSCHQHZLSJFNQ-QTVWNMPRSA-N 0.000 description 1
- 230000004543 DNA replication Effects 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 241001269524 Dura Species 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
- 241000196324 Embryophyta Species 0.000 description 1
- 108010067770 Endopeptidase K Proteins 0.000 description 1
- 229940122586 Enkephalinase inhibitor Drugs 0.000 description 1
- 241001492222 Epicoccum Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 208000015872 Gaucher disease Diseases 0.000 description 1
- 102100039289 Glial fibrillary acidic protein Human genes 0.000 description 1
- 101710193519 Glial fibrillary acidic protein Proteins 0.000 description 1
- 102000004547 Glucosylceramidase Human genes 0.000 description 1
- 108010017544 Glucosylceramidase Proteins 0.000 description 1
- 102000053187 Glucuronidase Human genes 0.000 description 1
- 108010060309 Glucuronidase Proteins 0.000 description 1
- 101710153310 Hemoglobin subunit beta-3 Proteins 0.000 description 1
- 102100038617 Hemoglobin subunit gamma-2 Human genes 0.000 description 1
- 208000028782 Hereditary disease Diseases 0.000 description 1
- 101000933465 Homo sapiens Beta-glucuronidase Proteins 0.000 description 1
- 101001045440 Homo sapiens Beta-hexosaminidase subunit alpha Proteins 0.000 description 1
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 description 1
- 241000701024 Human betaherpesvirus 5 Species 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 101150008942 J gene Proteins 0.000 description 1
- 235000008119 Larix laricina Nutrition 0.000 description 1
- 241000218653 Larix laricina Species 0.000 description 1
- 102000004317 Lyases Human genes 0.000 description 1
- 108090000856 Lyases Proteins 0.000 description 1
- 208000008771 Lymphadenopathy Diseases 0.000 description 1
- 241000283923 Marmota monax Species 0.000 description 1
- 101100297382 Mus musculus Dcn gene Proteins 0.000 description 1
- 206010056677 Nerve degeneration Diseases 0.000 description 1
- 201000000791 Niemann-Pick disease type B Diseases 0.000 description 1
- 241001282736 Oriens Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- ZPHBZEQOLSRPAK-UHFFFAOYSA-N Phosphoramidon Natural products C=1NC2=CC=CC=C2C=1CC(C(O)=O)NC(=O)C(CC(C)C)NP(O)(=O)OC1OC(C)C(O)C(O)C1O ZPHBZEQOLSRPAK-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 241000125945 Protoparvovirus Species 0.000 description 1
- 108091034057 RNA (poly(A)) Proteins 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 108700013394 SOD1 G93A Proteins 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- 108020004459 Small interfering RNA Proteins 0.000 description 1
- 208000029033 Spinal Cord disease Diseases 0.000 description 1
- 241001062472 Stokellia anisodon Species 0.000 description 1
- 241000701093 Suid alphaherpesvirus 1 Species 0.000 description 1
- 108010021188 Superoxide Dismutase-1 Proteins 0.000 description 1
- 102100038836 Superoxide dismutase [Cu-Zn] Human genes 0.000 description 1
- 208000022292 Tay-Sachs disease Diseases 0.000 description 1
- 108010036928 Thiorphan Proteins 0.000 description 1
- 240000002657 Thymus vulgaris Species 0.000 description 1
- 235000007303 Thymus vulgaris Nutrition 0.000 description 1
- 208000008291 Type B Niemann-Pick Disease Diseases 0.000 description 1
- 241000458243 Viana Species 0.000 description 1
- 108700005077 Viral Genes Proteins 0.000 description 1
- 108091093126 WHP Posttrascriptional Response Element Proteins 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 208000013228 adenopathy Diseases 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- WQZGKKKJIJFFOK-FPRJBGLDSA-N beta-D-galactose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-FPRJBGLDSA-N 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 230000006931 brain damage Effects 0.000 description 1
- 231100000874 brain damage Toxicity 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 210000001715 carotid artery Anatomy 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000027326 copulation Effects 0.000 description 1
- 210000003792 cranial nerve Anatomy 0.000 description 1
- 230000037029 cross reaction Effects 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 230000000120 cytopathologic effect Effects 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 230000002542 deteriorative effect Effects 0.000 description 1
- 102000038379 digestive enzymes Human genes 0.000 description 1
- 108091007734 digestive enzymes Proteins 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- QNDQILQPPKQROV-UHFFFAOYSA-N dizinc Chemical compound [Zn]=[Zn] QNDQILQPPKQROV-UHFFFAOYSA-N 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 239000002792 enkephalinase inhibitor Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 229940049268 euthasol Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000011990 functional testing Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000012239 gene modification Methods 0.000 description 1
- 230000005017 genetic modification Effects 0.000 description 1
- 235000013617 genetically modified food Nutrition 0.000 description 1
- 210000005046 glial fibrillary acidic protein Anatomy 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 108010021519 haematoporphyrin-bovine serum albumin conjugate Proteins 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 230000001744 histochemical effect Effects 0.000 description 1
- 102000057593 human F8 Human genes 0.000 description 1
- 238000011532 immunohistochemical staining Methods 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 210000004283 incisor Anatomy 0.000 description 1
- 230000001524 infective effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 description 1
- 229960000991 ketoprofen Drugs 0.000 description 1
- 238000009940 knitting Methods 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 210000005171 mammalian brain Anatomy 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000002398 materia medica Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 238000007491 morphometric analysis Methods 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 210000003061 neural cell Anatomy 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 230000007171 neuropathology Effects 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000006919 peptide aggregation Effects 0.000 description 1
- 108010072906 phosphoramidon Proteins 0.000 description 1
- BWSDNRQVTFZQQD-AYVHNPTNSA-N phosphoramidon Chemical compound O([P@@](O)(=O)N[C@H](CC(C)C)C(=O)N[C@H](CC=1[C]2C=CC=CC2=NC=1)C(O)=O)[C@H]1O[C@@H](C)[C@H](O)[C@@H](O)[C@@H]1O BWSDNRQVTFZQQD-AYVHNPTNSA-N 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 210000000063 presynaptic terminal Anatomy 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000018883 protein targeting Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 230000010837 receptor-mediated endocytosis Effects 0.000 description 1
- 229940047431 recombinate Drugs 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000010825 rotarod performance test Methods 0.000 description 1
- 210000000954 sacrococcygeal region Anatomy 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 239000007974 sodium acetate buffer Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 description 1
- LJJKNPQAGWVLDQ-SNVBAGLBSA-N thiorphan Chemical compound OC(=O)CNC(=O)[C@@H](CS)CC1=CC=CC=C1 LJJKNPQAGWVLDQ-SNVBAGLBSA-N 0.000 description 1
- 239000001585 thymus vulgaris Substances 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 230000010415 tropism Effects 0.000 description 1
- 230000005641 tunneling Effects 0.000 description 1
- 210000005111 ventral hippocampus Anatomy 0.000 description 1
- 210000001835 viscera Anatomy 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
- 210000004885 white matter Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—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
- C12N15/86—Viral vectors
-
- 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
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- 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
- 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
-
- 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
- C12N15/86—Viral vectors
- C12N15/864—Parvoviral vectors, e.g. parvovirus, densovirus
- C12N15/8645—Adeno-associated virus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- 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
- C12N2750/14041—Use of virus, viral particle or viral elements as a 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
-
- 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
- C12N2799/00—Uses of viruses
- C12N2799/02—Uses of viruses as vector
- C12N2799/021—Uses of viruses as vector for the expression of a heterologous nucleic acid
- C12N2799/025—Uses of viruses as vector for the expression of a heterologous nucleic acid where the vector is derived from a parvovirus
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- Zoology (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Molecular Biology (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Virology (AREA)
- Epidemiology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Obesity (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Toxicology (AREA)
- Gastroenterology & Hepatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US67705705P | 2005-05-02 | 2005-05-02 | |
| US60/677,057 | 2005-05-02 | ||
| US68580805P | 2005-05-31 | 2005-05-31 | |
| US60/685,808 | 2005-05-31 | ||
| CNA2006800237754A CN101212988A (zh) | 2005-05-02 | 2006-05-02 | 神经代谢疾病的基因治疗 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2006800237754A Division CN101212988A (zh) | 2005-05-02 | 2006-05-02 | 神经代谢疾病的基因治疗 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107007842A true CN107007842A (zh) | 2017-08-04 |
Family
ID=37308324
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2006800237754A Pending CN101212988A (zh) | 2005-05-02 | 2006-05-02 | 神经代谢疾病的基因治疗 |
| CN201410483749.6A Pending CN104306986A (zh) | 2005-05-02 | 2006-05-02 | 神经代谢疾病的基因治疗 |
| CN201710506914.9A Pending CN107362371A (zh) | 2005-05-02 | 2006-05-02 | 神经代谢疾病的基因治疗 |
| CN201611031204.7A Pending CN107007842A (zh) | 2005-05-02 | 2006-05-02 | 神经代谢疾病的基因治疗 |
Family Applications Before (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2006800237754A Pending CN101212988A (zh) | 2005-05-02 | 2006-05-02 | 神经代谢疾病的基因治疗 |
| CN201410483749.6A Pending CN104306986A (zh) | 2005-05-02 | 2006-05-02 | 神经代谢疾病的基因治疗 |
| CN201710506914.9A Pending CN107362371A (zh) | 2005-05-02 | 2006-05-02 | 神经代谢疾病的基因治疗 |
Country Status (13)
| Country | Link |
|---|---|
| US (2) | US10632213B2 (enExample) |
| EP (4) | EP3520823B1 (enExample) |
| JP (3) | JP5829372B2 (enExample) |
| CN (4) | CN101212988A (enExample) |
| AT (1) | ATE525092T1 (enExample) |
| AU (1) | AU2006243776A1 (enExample) |
| BR (1) | BRPI0611379A2 (enExample) |
| CA (2) | CA2607173C (enExample) |
| ES (1) | ES2887076T3 (enExample) |
| IL (2) | IL187078A (enExample) |
| PL (4) | PL2420256T3 (enExample) |
| PT (4) | PT1879624E (enExample) |
| WO (1) | WO2006119458A1 (enExample) |
Families Citing this family (39)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3302529B2 (ja) | 1995-04-28 | 2002-07-15 | 株式会社クボタ | ポンプ吸水槽の整流装置 |
| PL1879623T3 (pl) * | 2005-05-02 | 2013-03-29 | Genzyme Corp | Terapia genowa zaburzeń rdzenia kręgowego |
| CN101212988A (zh) | 2005-05-02 | 2008-07-02 | 建新公司 | 神经代谢疾病的基因治疗 |
| PL2489733T3 (pl) | 2006-06-07 | 2019-08-30 | Genzyme Corporation | Terapia genowa w stwardnieniu zanikowym bocznym i innych zaburzeniach rdzenia kręgowego |
| ES2905616T3 (es) | 2007-06-06 | 2022-04-11 | Genzyme Corp | Terapia génica para enfermedades de almacenamiento lisosómico |
| EP2687609B1 (en) | 2008-11-10 | 2017-01-04 | The United States of America, as represented by The Secretary, Department of Health and Human Services | Method for treating solid tumor |
| DK3421603T3 (da) | 2009-05-02 | 2022-01-10 | Genzyme Corp | Genterapi for neurodegenerative forstyrrelser |
| US9150926B2 (en) | 2010-12-06 | 2015-10-06 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Diagnosis and treatment of adrenocortical tumors using human microRNA-483 |
| WO2012145646A1 (en) * | 2011-04-20 | 2012-10-26 | Miguel Sena-Esteves | Methods for the treatment of tay-sachs disease, sandhoff disease, and gmi-gangliosidosis |
| WO2015191508A1 (en) | 2014-06-09 | 2015-12-17 | Voyager Therapeutics, Inc. | Chimeric capsids |
| RU2716991C2 (ru) | 2014-11-05 | 2020-03-17 | Вояджер Терапьютикс, Инк. | Полинуклеотиды aadc для лечения болезни паркинсона |
| CN112410339A (zh) | 2014-11-14 | 2021-02-26 | 沃雅戈治疗公司 | 调节性多核苷酸 |
| RU2716422C2 (ru) | 2014-11-14 | 2020-03-11 | Вояджер Терапьютикс, Инк. | Композиции и способы лечения бокового амиотрофического склероза (als) |
| WO2016081924A1 (en) * | 2014-11-20 | 2016-05-26 | Duke University | Compositions, systems and methods for cell therapy |
| HK1245326A1 (zh) | 2014-12-12 | 2018-08-24 | Voyager Therapeutics, Inc. | 用於生产scaav的组合物和方法 |
| CA2976082A1 (en) * | 2015-02-10 | 2016-08-18 | Genzyme Corporation | Enhanced delivery of viral particles to the striatum and cortex |
| JP6659050B2 (ja) * | 2015-03-26 | 2020-03-04 | スーヂョウ アウゾン バイオロジカル テクノロジー カンパニー, リミテッド | P75ecd及び/又はp75による神経学的障害の診断又は処置方法 |
| GB201508025D0 (en) | 2015-05-11 | 2015-06-24 | Ucl Business Plc | Fabry disease gene therapy |
| US11027024B2 (en) | 2015-05-29 | 2021-06-08 | University Of Iowa Research Foundation | Methods of delivery of transgenes for treating brain diseases |
| WO2017189964A2 (en) | 2016-04-29 | 2017-11-02 | Voyager Therapeutics, Inc. | Compositions for the treatment of disease |
| WO2017189959A1 (en) | 2016-04-29 | 2017-11-02 | Voyager Therapeutics, Inc. | Compositions for the treatment of disease |
| CA3252099A1 (en) | 2016-05-18 | 2025-06-05 | Voyager Therapeutics, Inc. | MODULATING POLYNUCLEOTIDES |
| CN109831916B (zh) | 2016-05-18 | 2023-07-21 | 沃雅戈治疗公司 | 治疗亨廷顿氏舞蹈病的组合物和方法 |
| EP3506817A4 (en) | 2016-08-30 | 2020-07-22 | The Regents of The University of California | Methods for biomedical targeting and delivery and devices and systems for practicing the same |
| JOP20190200A1 (ar) | 2017-02-28 | 2019-08-27 | Univ Pennsylvania | تركيبات نافعة في معالجة ضمور العضل النخاعي |
| JP2020518258A (ja) | 2017-05-05 | 2020-06-25 | ボイジャー セラピューティクス インコーポレイテッドVoyager Therapeutics,Inc. | 筋萎縮性側索硬化症(als)治療組成物および方法 |
| JP2020518259A (ja) | 2017-05-05 | 2020-06-25 | ボイジャー セラピューティクス インコーポレイテッドVoyager Therapeutics,Inc. | ハンチントン病治療組成物および方法 |
| EP3635009A1 (en) | 2017-06-07 | 2020-04-15 | Regeneron Pharmaceuticals, Inc. | Compositions and methods for internalizing enzymes |
| JOP20190269A1 (ar) | 2017-06-15 | 2019-11-20 | Voyager Therapeutics Inc | بولي نوكليوتيدات aadc لعلاج مرض باركنسون |
| WO2019018342A1 (en) | 2017-07-17 | 2019-01-24 | Voyager Therapeutics, Inc. | NETWORK EQUIPMENT TRACK GUIDE SYSTEM |
| KR102850887B1 (ko) | 2017-08-03 | 2025-08-28 | 보이저 테라퓨틱스, 인크. | Aav의 전달을 위한 조성물 및 방법 |
| MX2020003042A (es) | 2017-09-29 | 2020-11-18 | Voyager Therapeutics Inc | Rescate del fenotipo neurológico central y periférico de la ataxia de friedreich mediante administración intravenosa. |
| CN119242711A (zh) | 2017-10-16 | 2025-01-03 | 沃雅戈治疗公司 | 肌萎缩性侧索硬化症(als)的治疗 |
| US20200237799A1 (en) | 2017-10-16 | 2020-07-30 | Voyager Therapeutics, Inc. | Treatment of amyotrophic lateral sclerosis (als) |
| IL322464A (en) | 2018-02-07 | 2025-09-01 | Regeneron Pharma | Methods and compositions for administering therapeutic protein |
| BR112020023082A2 (pt) | 2018-05-15 | 2021-02-09 | Voyager Therapeutics, Inc. | composições e métodos para o tratamento de doença de parkinson |
| EP3793591A1 (en) | 2018-05-17 | 2021-03-24 | Regeneron Pharmaceuticals, Inc. | Anti-cd63 antibodies, conjugates, and uses thereof |
| CA3114621A1 (en) | 2018-09-28 | 2020-04-02 | Voyager Therapeutics, Inc. | Frataxin expression constructs having engineered promoters and methods of use thereof |
| KR20240126916A (ko) * | 2023-02-14 | 2024-08-22 | 경북대학교 산학협력단 | Asm 단백질 또는 이의 단편을 포함하는 퇴행성 신경질환 또는 우울증 예방 또는 치료용 조성물 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040258666A1 (en) * | 2003-05-01 | 2004-12-23 | Passini Marco A. | Gene therapy for neurometabolic disorders |
| CN1575340A (zh) * | 2001-08-29 | 2005-02-02 | 田边制药株式会社 | 用于治疗神经退行性疾病的组合物和方法 |
Family Cites Families (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE8303626D0 (sv) | 1983-06-23 | 1983-06-23 | Kabigen Ab | A recombinant plasmid a transformant microorganism, a polydoxyrebonucleotide segment, a process for producing a biologically active protein, and the protein thus produced |
| US5672344A (en) | 1987-12-30 | 1997-09-30 | The Regents Of The University Of Michigan | Viral-mediated gene transfer system |
| US5773278A (en) | 1991-05-03 | 1998-06-30 | Mount Sinai Medical Center | Acid sphingomyelinase gene |
| AU687829B2 (en) | 1993-06-24 | 1998-03-05 | Advec, Inc. | Adenovirus vectors for gene therapy |
| JP3875990B2 (ja) | 1993-10-25 | 2007-01-31 | カンジ,インコーポレイテッド | 組換えアデノウイルスベクターおよび使用方法 |
| ES2216005T3 (es) | 1993-11-09 | 2004-10-16 | Targeted Genetics Corporation | Produccion de titulos elevados de vectores de aav recombinantes. |
| US7252989B1 (en) | 1994-04-04 | 2007-08-07 | Board Of Regents, The University Of Texas System | Adenovirus supervector system |
| EP0755454B1 (en) | 1994-04-13 | 2008-02-13 | The Rockefeller University | Aav-mediated delivery of dna to cells of the nervous system |
| AU1525797A (en) | 1996-04-22 | 1997-11-12 | Medtronic, Inc. | Two-stage angled venous cannula |
| US6544785B1 (en) | 1998-09-14 | 2003-04-08 | Mount Sinai School Of Medicine Of New York University | Helper-free rescue of recombinant negative strand RNA viruses |
| WO2001036603A2 (en) * | 1999-11-17 | 2001-05-25 | Avigen, Inc. | Recombinant adeno-associated virus virions for the treatment of lysosomal disorders |
| US20030165481A1 (en) * | 2000-02-24 | 2003-09-04 | Hersh Louis B. | Amyloid peptide inactivating enzyme to treat Alzheimer's disease |
| AU2001290984A1 (en) | 2000-09-18 | 2002-04-02 | Genzyme Corporation | Expression vectors containing hybrid ubiquitin promoters |
| US7232670B2 (en) * | 2001-09-28 | 2007-06-19 | St. Jude Children's Research Hospital | Targeting proteins to cells expressing mannose receptors via expression in insect cells |
| PT2359869T (pt) | 2001-12-17 | 2019-04-16 | Univ Pennsylvania | Sequências do vírus adeno-associado (aav) do serotipo 8, vetores contendo as mesmas, e utilizações destas |
| CA2471812C (en) | 2001-12-21 | 2012-09-04 | The Salk Institute For Biological Studies | Targeted retrograde gene delivery to motor neurons |
| US6998118B2 (en) | 2001-12-21 | 2006-02-14 | The Salk Institute For Biological Studies | Targeted retrograde gene delivery for neuronal protection |
| US7807618B2 (en) * | 2002-05-20 | 2010-10-05 | The Board Of Regents Of The University Of Texas System | Methods and compositions for delivering enzymes and nucleic acid molecules to brain, bone and other tissues |
| PL1620133T3 (pl) * | 2003-05-01 | 2016-05-31 | Genzyme Corp | Terapia genowa dla zaburzeń neurometabolicznych |
| US7740168B2 (en) | 2003-08-18 | 2010-06-22 | Visa U.S.A. Inc. | Method and system for generating a dynamic verification value |
| US20070275449A1 (en) | 2003-10-15 | 2007-11-29 | Vector Gene Technology Company Ltd. | Method for Large-Scale Production, Isolation, Purification and the Uses of Multi-Type Recombinant Adeno-Associated Virus Vectors |
| EP1716870A1 (en) | 2005-04-29 | 2006-11-02 | Bracco Imaging S.p.A. | MRI contrast agents endowed with concentration independent responsiveness |
| CN101212988A (zh) | 2005-05-02 | 2008-07-02 | 建新公司 | 神经代谢疾病的基因治疗 |
| PL1879623T3 (pl) | 2005-05-02 | 2013-03-29 | Genzyme Corp | Terapia genowa zaburzeń rdzenia kręgowego |
| MX360595B (es) | 2006-02-08 | 2018-11-09 | Genzyme Corp | Terapia génica para la enfermedad de niemann-pick de tipo a. |
| KR20200016407A (ko) | 2011-05-16 | 2020-02-14 | 젠자임 코포레이션 | Cxcr4 길항제의 용도 |
| TWI821227B (zh) | 2017-12-22 | 2023-11-11 | 美商健臻公司 | 胺甲喋呤誘發的免疫耐受性之生物標記 |
-
2006
- 2006-05-02 CN CNA2006800237754A patent/CN101212988A/zh active Pending
- 2006-05-02 PT PT06759081T patent/PT1879624E/pt unknown
- 2006-05-02 WO PCT/US2006/017242 patent/WO2006119458A1/en not_active Ceased
- 2006-05-02 PT PT19153520T patent/PT3520823T/pt unknown
- 2006-05-02 EP EP19153520.2A patent/EP3520823B1/en active Active
- 2006-05-02 PL PL11169633.2T patent/PL2420256T3/pl unknown
- 2006-05-02 AU AU2006243776A patent/AU2006243776A1/en not_active Abandoned
- 2006-05-02 EP EP16162716.1A patent/EP3058959B1/en active Active
- 2006-05-02 AT AT06759081T patent/ATE525092T1/de not_active IP Right Cessation
- 2006-05-02 PT PT16162716T patent/PT3058959T/pt unknown
- 2006-05-02 PL PL16162716T patent/PL3058959T3/pl unknown
- 2006-05-02 PT PT111696332T patent/PT2420256T/pt unknown
- 2006-05-02 JP JP2008510224A patent/JP5829372B2/ja active Active
- 2006-05-02 ES ES19153520T patent/ES2887076T3/es active Active
- 2006-05-02 CA CA2607173A patent/CA2607173C/en active Active
- 2006-05-02 PL PL06759081T patent/PL1879624T3/pl unknown
- 2006-05-02 CN CN201410483749.6A patent/CN104306986A/zh active Pending
- 2006-05-02 PL PL19153520T patent/PL3520823T3/pl unknown
- 2006-05-02 CN CN201710506914.9A patent/CN107362371A/zh active Pending
- 2006-05-02 BR BRPI0611379-6A patent/BRPI0611379A2/pt not_active Application Discontinuation
- 2006-05-02 CA CA2998603A patent/CA2998603C/en active Active
- 2006-05-02 CN CN201611031204.7A patent/CN107007842A/zh active Pending
- 2006-05-02 EP EP06759081A patent/EP1879624B1/en active Active
- 2006-05-02 EP EP11169633.2A patent/EP2420256B1/en active Active
-
2007
- 2007-11-01 IL IL187078A patent/IL187078A/en not_active IP Right Cessation
- 2007-11-02 US US11/934,325 patent/US10632213B2/en active Active
-
2013
- 2013-09-27 JP JP2013201138A patent/JP2014037418A/ja active Pending
-
2015
- 2015-06-03 IL IL239167A patent/IL239167A0/en unknown
- 2015-10-02 JP JP2015197051A patent/JP6338560B2/ja active Active
-
2020
- 2020-03-03 US US16/808,206 patent/US11957765B2/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1575340A (zh) * | 2001-08-29 | 2005-02-02 | 田边制药株式会社 | 用于治疗神经退行性疾病的组合物和方法 |
| US20040258666A1 (en) * | 2003-05-01 | 2004-12-23 | Passini Marco A. | Gene therapy for neurometabolic disorders |
Non-Patent Citations (2)
| Title |
|---|
| CORINNA BURGER ET AL.,: "Recombinant AAV Viral Vectors Pseudotyped with Viral Capsids from Serotypes 1, 2, and 5 Display Differential Efficiency and Cell Tropism after Delivery to Different Regions of the Central Nervous System", 《MOLECULAR THERAPY》 * |
| CORINNA LEBHERZ等: "Gene therapy with novel adeno-associated virus vectors substantially diminishes atherosclerosis in a murine model of familial hypercholesterolemia", 《THE JOURNAL OF GENE MEDICINE》 * |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107007842A (zh) | 神经代谢疾病的基因治疗 | |
| US10913956B2 (en) | Gene therapy for neurometabolic disorders | |
| DK1620133T3 (en) | GENE THERAPY FOR NEURO metabolic diseases | |
| US20060171926A1 (en) | Gene therapy for neurometabolic disorders |
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 |