CA3166104A1 - Systemes de therapie genique et methodes associees pour le traitement d'une perte de l'audition - Google Patents
Systemes de therapie genique et methodes associees pour le traitement d'une perte de l'audition Download PDFInfo
- Publication number
- CA3166104A1 CA3166104A1 CA3166104A CA3166104A CA3166104A1 CA 3166104 A1 CA3166104 A1 CA 3166104A1 CA 3166104 A CA3166104 A CA 3166104A CA 3166104 A CA3166104 A CA 3166104A CA 3166104 A1 CA3166104 A1 CA 3166104A1
- Authority
- CA
- Canada
- Prior art keywords
- promoters
- vector
- tmprss3
- hearing loss
- gene
- 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
- 208000016354 hearing loss disease Diseases 0.000 title claims abstract description 135
- 206010011878 Deafness Diseases 0.000 title claims abstract description 132
- 230000010370 hearing loss Effects 0.000 title claims abstract description 103
- 231100000888 hearing loss Toxicity 0.000 title claims abstract description 103
- 238000000034 method Methods 0.000 title claims abstract description 47
- 238000011282 treatment Methods 0.000 title claims description 25
- 238000001415 gene therapy Methods 0.000 title abstract description 36
- 101000798700 Homo sapiens Transmembrane protease serine 3 Proteins 0.000 claims abstract description 95
- 230000035772 mutation Effects 0.000 claims abstract description 94
- 101000798702 Homo sapiens Transmembrane protease serine 4 Proteins 0.000 claims abstract description 77
- 239000007943 implant Substances 0.000 claims abstract description 54
- 239000013598 vector Substances 0.000 claims abstract description 39
- 210000003027 ear inner Anatomy 0.000 claims abstract description 26
- 238000002513 implantation Methods 0.000 claims abstract description 26
- 101100343697 Homo sapiens LOXHD1 gene Proteins 0.000 claims abstract description 14
- 239000000203 mixture Substances 0.000 claims abstract description 5
- 102100032454 Transmembrane protease serine 3 Human genes 0.000 claims description 78
- 108090000623 proteins and genes Proteins 0.000 claims description 55
- 210000004027 cell Anatomy 0.000 claims description 36
- 239000013603 viral vector Substances 0.000 claims description 35
- 239000013604 expression vector Substances 0.000 claims description 27
- 241000702423 Adeno-associated virus - 2 Species 0.000 claims description 24
- 241000701024 Human betaherpesvirus 5 Species 0.000 claims description 16
- 230000002068 genetic effect Effects 0.000 claims description 15
- 241001634120 Adeno-associated virus - 5 Species 0.000 claims description 12
- 241000972680 Adeno-associated virus - 6 Species 0.000 claims description 12
- 241001164823 Adeno-associated virus - 7 Species 0.000 claims description 12
- 241001164825 Adeno-associated virus - 8 Species 0.000 claims description 12
- 101000834253 Gallus gallus Actin, cytoplasmic 1 Proteins 0.000 claims description 12
- 239000003623 enhancer Substances 0.000 claims description 12
- 230000001225 therapeutic effect Effects 0.000 claims description 11
- 230000014509 gene expression Effects 0.000 claims description 10
- 239000012528 membrane Substances 0.000 claims description 7
- 210000004379 membrane Anatomy 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 241000202702 Adeno-associated virus - 3 Species 0.000 claims description 6
- 241000580270 Adeno-associated virus - 4 Species 0.000 claims description 6
- 241000701022 Cytomegalovirus Species 0.000 claims description 6
- 108091034057 RNA (poly(A)) Proteins 0.000 claims description 6
- 210000001062 endolymphatic sac Anatomy 0.000 claims description 6
- 101150016977 pou4f3 gene Proteins 0.000 claims description 6
- 241001655883 Adeno-associated virus - 1 Species 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 5
- 238000002347 injection Methods 0.000 claims description 4
- 239000007924 injection Substances 0.000 claims description 4
- 210000000130 stem cell Anatomy 0.000 claims description 4
- 210000000262 cochlear duct Anatomy 0.000 claims description 3
- 210000004263 induced pluripotent stem cell Anatomy 0.000 claims description 2
- 210000002768 hair cell Anatomy 0.000 abstract description 52
- 231100000895 deafness Toxicity 0.000 abstract description 26
- 101001043326 Homo sapiens Lipoxygenase homology domain-containing protein 1 Proteins 0.000 abstract description 24
- 102100021959 Lipoxygenase homology domain-containing protein 1 Human genes 0.000 abstract description 23
- 239000003814 drug Substances 0.000 abstract description 10
- 230000000694 effects Effects 0.000 abstract description 5
- 238000001476 gene delivery Methods 0.000 abstract description 5
- 230000004083 survival effect Effects 0.000 abstract description 3
- 230000003612 virological effect Effects 0.000 abstract 1
- 210000001323 spiral ganglion Anatomy 0.000 description 33
- 150000007523 nucleic acids Chemical group 0.000 description 29
- 241000699670 Mus sp. Species 0.000 description 28
- 108091028043 Nucleic acid sequence Proteins 0.000 description 23
- 241000699666 Mus <mouse, genus> Species 0.000 description 18
- 230000006870 function Effects 0.000 description 17
- 102000004169 proteins and genes Human genes 0.000 description 13
- 238000012360 testing method Methods 0.000 description 13
- 208000036201 autosomal recessive hearing loss Diseases 0.000 description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 12
- 206010010356 Congenital anomaly Diseases 0.000 description 11
- 241000282412 Homo Species 0.000 description 11
- 230000007850 degeneration Effects 0.000 description 10
- 201000010099 disease Diseases 0.000 description 9
- 230000000750 progressive effect Effects 0.000 description 9
- 210000003477 cochlea Anatomy 0.000 description 8
- 230000003915 cell function Effects 0.000 description 7
- 210000000860 cochlear nerve Anatomy 0.000 description 7
- 239000002299 complementary DNA Substances 0.000 description 7
- 238000010172 mouse model Methods 0.000 description 7
- 206010011891 Deafness neurosensory Diseases 0.000 description 6
- 101100260870 Mus musculus Tmprss3 gene Proteins 0.000 description 6
- 208000009966 Sensorineural Hearing Loss Diseases 0.000 description 6
- 210000000349 chromosome Anatomy 0.000 description 6
- 201000006790 nonsyndromic deafness Diseases 0.000 description 6
- 230000008439 repair process Effects 0.000 description 6
- 231100000879 sensorineural hearing loss Toxicity 0.000 description 6
- 208000023573 sensorineural hearing loss disease Diseases 0.000 description 6
- 241001362551 Samba Species 0.000 description 5
- 230000002950 deficient Effects 0.000 description 5
- 230000002939 deleterious effect Effects 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 230000018109 developmental process Effects 0.000 description 5
- 210000002569 neuron Anatomy 0.000 description 5
- 108020004707 nucleic acids Proteins 0.000 description 5
- 102000039446 nucleic acids Human genes 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 239000013607 AAV vector Substances 0.000 description 4
- 101710136259 E3 ubiquitin-protein ligase XIAP Proteins 0.000 description 4
- 102000011104 Wiskott-Aldrich Syndrome Protein Family Human genes 0.000 description 4
- 108010062653 Wiskott-Aldrich Syndrome Protein Family Proteins 0.000 description 4
- 102000050257 X-Linked Inhibitor of Apoptosis Human genes 0.000 description 4
- 239000013543 active substance Substances 0.000 description 4
- 208000033022 autosomal recessive nonsyndromic hearing loss 77 Diseases 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 230000004064 dysfunction Effects 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- 230000002797 proteolythic effect Effects 0.000 description 4
- 230000008685 targeting Effects 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- 241001406376 Betasatellite Species 0.000 description 3
- 102100022509 Cadherin-23 Human genes 0.000 description 3
- 101000899442 Homo sapiens Cadherin-23 Proteins 0.000 description 3
- 101000801040 Homo sapiens Transmembrane channel-like protein 1 Proteins 0.000 description 3
- 101000764625 Homo sapiens Transmembrane inner ear expressed protein Proteins 0.000 description 3
- 208000026350 Inborn Genetic disease Diseases 0.000 description 3
- 101100460719 Mus musculus Noto gene Proteins 0.000 description 3
- FUSGACRLAFQQRL-UHFFFAOYSA-N N-Ethyl-N-nitrosourea Chemical compound CCN(N=O)C(N)=O FUSGACRLAFQQRL-UHFFFAOYSA-N 0.000 description 3
- 102000035195 Peptidases Human genes 0.000 description 3
- 108091005804 Peptidases Proteins 0.000 description 3
- 239000004365 Protease Substances 0.000 description 3
- 102100033690 Transmembrane channel-like protein 1 Human genes 0.000 description 3
- 102100026225 Transmembrane inner ear expressed protein Human genes 0.000 description 3
- -1 USHIC Proteins 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 201000006140 autosomal recessive nonsyndromic deafness 77 Diseases 0.000 description 3
- 238000002648 combination therapy Methods 0.000 description 3
- 230000003111 delayed effect Effects 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 238000012377 drug delivery Methods 0.000 description 3
- 208000016361 genetic disease Diseases 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- 230000035800 maturation Effects 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 102220015155 rs181949335 Human genes 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 238000011752 CBA/J (JAX™ mouse strain) Methods 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 241000702421 Dependoparvovirus Species 0.000 description 2
- 206010064571 Gene mutation Diseases 0.000 description 2
- 208000032041 Hearing impaired Diseases 0.000 description 2
- 208000009889 Herpes Simplex Diseases 0.000 description 2
- 101100260869 Homo sapiens TMPRSS3 gene Proteins 0.000 description 2
- 206010048865 Hypoacusis Diseases 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 102000012479 Serine Proteases Human genes 0.000 description 2
- 108010022999 Serine Proteases Proteins 0.000 description 2
- 108700019146 Transgenes Proteins 0.000 description 2
- 206010046865 Vaccinia virus infection Diseases 0.000 description 2
- 150000001413 amino acids Chemical group 0.000 description 2
- 210000003484 anatomy Anatomy 0.000 description 2
- 210000003030 auditory receptor cell Anatomy 0.000 description 2
- 230000002146 bilateral effect Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 230000006735 deficit Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 210000000883 ear external Anatomy 0.000 description 2
- 238000010304 firing Methods 0.000 description 2
- 230000008717 functional decline Effects 0.000 description 2
- 230000009395 genetic defect Effects 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 102000045778 human TMPRSS3 Human genes 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 210000002985 organ of corti Anatomy 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 102220000180 rs121918370 Human genes 0.000 description 2
- 102200098637 rs137852999 Human genes 0.000 description 2
- 102200098636 rs137853000 Human genes 0.000 description 2
- 102220310832 rs1555783543 Human genes 0.000 description 2
- 102220016868 rs188119157 Human genes 0.000 description 2
- 102220238149 rs200090033 Human genes 0.000 description 2
- 102200098592 rs201632198 Human genes 0.000 description 2
- 102200098628 rs28939084 Human genes 0.000 description 2
- 102220054519 rs372526764 Human genes 0.000 description 2
- 102200098604 rs387906915 Human genes 0.000 description 2
- 102220054817 rs727505104 Human genes 0.000 description 2
- 238000009118 salvage therapy Methods 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 238000011830 transgenic mouse model Methods 0.000 description 2
- 230000010415 tropism Effects 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 241000701161 unidentified adenovirus Species 0.000 description 2
- 208000007089 vaccinia Diseases 0.000 description 2
- ZGBKEOLAPVBJFC-DJLDLDEBSA-N 1-[(2r,4s,5r)-5-(hydroxymethyl)-4-methoxyoxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O1[C@H](CO)[C@@H](OC)C[C@@H]1N1C(=O)NC(=O)C(C)=C1 ZGBKEOLAPVBJFC-DJLDLDEBSA-N 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- 101710092462 Alpha-hemolysin Proteins 0.000 description 1
- 102100040191 Alpha-tectorin Human genes 0.000 description 1
- 101710197219 Alpha-toxin Proteins 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 229910052688 Gadolinium Inorganic materials 0.000 description 1
- 208000003098 Ganglion Cysts Diseases 0.000 description 1
- 208000034826 Genetic Predisposition to Disease Diseases 0.000 description 1
- 208000016621 Hearing disease Diseases 0.000 description 1
- 101000889766 Homo sapiens Alpha-tectorin Proteins 0.000 description 1
- 102100023915 Insulin Human genes 0.000 description 1
- 241000713666 Lentivirus Species 0.000 description 1
- 101710123264 Lipoxygenase homology domain-containing protein 1 Proteins 0.000 description 1
- 102000003820 Lipoxygenases Human genes 0.000 description 1
- 108090000128 Lipoxygenases Proteins 0.000 description 1
- 101150010734 Loxhd1 gene Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 208000027530 Meniere disease Diseases 0.000 description 1
- 241000122159 Modiolus Species 0.000 description 1
- 101100343698 Mus musculus Loxhd1 gene Proteins 0.000 description 1
- 108020004485 Nonsense Codon Proteins 0.000 description 1
- 206010033109 Ototoxicity Diseases 0.000 description 1
- 101710124951 Phospholipase C Proteins 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 206010040030 Sensory loss Diseases 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- 208000005400 Synovial Cyst Diseases 0.000 description 1
- 108010004408 TRPP Cation Channels Proteins 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 208000019467 X-linked deafness Diseases 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 239000002776 alpha toxin Substances 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 201000005823 autosomal dominant nonsyndromic deafness 12 Diseases 0.000 description 1
- 208000034083 autosomal dominant nonsyndromic hearing loss 12 Diseases 0.000 description 1
- 210000000133 brain stem Anatomy 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000005056 cell body Anatomy 0.000 description 1
- 230000006727 cell loss Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000005101 cell tropism Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 208000013407 communication difficulty Diseases 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000005786 degenerative changes Effects 0.000 description 1
- 238000002716 delivery method Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- JXSJBGJIGXNWCI-UHFFFAOYSA-N diethyl 2-[(dimethoxyphosphorothioyl)thio]succinate Chemical compound CCOC(=O)CC(SP(=S)(OC)OC)C(=O)OCC JXSJBGJIGXNWCI-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 210000005069 ears Anatomy 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000000763 evoking effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 description 1
- 238000012252 genetic analysis Methods 0.000 description 1
- 210000004307 hair cells vestibular Anatomy 0.000 description 1
- 230000003676 hair loss Effects 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 238000007901 in situ hybridization Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 210000000067 inner hair cell Anatomy 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000036244 malformation Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 230000008904 neural response Effects 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000003955 neuronal function Effects 0.000 description 1
- 231100001098 no ototoxicity Toxicity 0.000 description 1
- 230000037434 nonsense mutation Effects 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000004789 organ system Anatomy 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 231100000262 ototoxicity Toxicity 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 102000054765 polymorphisms of proteins Human genes 0.000 description 1
- 230000002250 progressing effect Effects 0.000 description 1
- 230000000135 prohibitive effect Effects 0.000 description 1
- 210000003370 receptor cell Anatomy 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 102220015147 rs147231991 Human genes 0.000 description 1
- 102220054691 rs373937326 Human genes 0.000 description 1
- 102220297961 rs397517376 Human genes 0.000 description 1
- 102200098632 rs56264519 Human genes 0.000 description 1
- 102220054698 rs727503146 Human genes 0.000 description 1
- 102220054522 rs727503493 Human genes 0.000 description 1
- 102220054410 rs727504304 Human genes 0.000 description 1
- 102220008026 rs75949023 Human genes 0.000 description 1
- 230000022932 ruffle assembly Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 210000002265 sensory receptor cell Anatomy 0.000 description 1
- 102000027509 sensory receptors Human genes 0.000 description 1
- 108091008691 sensory receptors Proteins 0.000 description 1
- 210000002205 spiral ligament of cochlea Anatomy 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 210000000645 stria vascularis Anatomy 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000001360 synchronised effect Effects 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 101150065190 term gene Proteins 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000006276 transfer reaction Methods 0.000 description 1
- 238000013520 translational research Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 230000001720 vestibular Effects 0.000 description 1
- 208000027491 vestibular disease Diseases 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
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
- A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
- A61N1/36036—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation of the outer, middle or inner ear
- A61N1/36038—Cochlear stimulation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- 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
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/02—Details
- A61N1/04—Electrodes
- A61N1/05—Electrodes for implantation or insertion into the body, e.g. heart electrode
- A61N1/0526—Head electrodes
- A61N1/0541—Cochlear electrodes
-
- 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)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Otolaryngology (AREA)
- Biotechnology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Zoology (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Radiology & Medical Imaging (AREA)
- Molecular Biology (AREA)
- Plant Pathology (AREA)
- Biochemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Virology (AREA)
- Biophysics (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Materials For Medical Uses (AREA)
Abstract
La présente invention concerne des systèmes de thérapie génique, et des méthodes associées, utiles pour traiter et/ou prévenir la surdité causée par une mutation génétique du gène TMPRSS3 ou du gène LOXHD1. Les compositions et les méthodes de la présente invention utilisent l'administration de gènes de TRMPSS3 ou de LOXHD1 par un vecteur viral adéno-associé (AAV) dans l'oreille interne afin de restaurer l'activité du gène TMPRSS3 ou du gène LOXHD1, respectivement, de favoriser la survie des cellules ciliées et de restaurer l'audition chez les patients souffrant de perte auditive. Selon la présente invention, les systèmes et méthodes peuvent faire appel à une combinaison de thérapie génique (par exemple, la thérapeutique moléculaire) pour la perte auditive causée par une mutation génétique, ainsi qu'à la mise en place d'un implant cochléaire.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US16/783,148 | 2020-02-05 | ||
| US16/783,148 US20200181596A1 (en) | 2017-03-17 | 2020-02-05 | Gene therapy systems and related methods for treatment of hearing loss |
| PCT/US2021/016653 WO2021158814A1 (fr) | 2020-02-05 | 2021-02-04 | Systèmes de thérapie génique et méthodes associées pour le traitement d'une perte de l'audition |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3166104A1 true CA3166104A1 (fr) | 2021-08-12 |
Family
ID=77200377
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3166104A Pending CA3166104A1 (fr) | 2020-02-05 | 2021-02-04 | Systemes de therapie genique et methodes associees pour le traitement d'une perte de l'audition |
Country Status (9)
| Country | Link |
|---|---|
| EP (1) | EP4081232A4 (fr) |
| JP (1) | JP2023513116A (fr) |
| KR (1) | KR20220137652A (fr) |
| CN (1) | CN116096391A (fr) |
| AU (1) | AU2021216405A1 (fr) |
| BR (1) | BR112022015345A2 (fr) |
| CA (1) | CA3166104A1 (fr) |
| IL (1) | IL295265A (fr) |
| WO (1) | WO2021158814A1 (fr) |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7186699B2 (en) * | 2003-06-03 | 2007-03-06 | Cell Genesys, Inc. | Method for treating cancer by vector-mediated delivery of one or more anti-angiogenic or pro-apoptotic genes |
| US9265933B2 (en) * | 2005-09-08 | 2016-02-23 | Massachusetts Eye And Ear Infirmary | Cochlear implants containing biological cells and uses thereof |
| WO2018170402A1 (fr) * | 2017-03-17 | 2018-09-20 | Rescue Hearing Inc | Constructions pour thérapie génique et procédés de traitement de la perte auditive |
-
2021
- 2021-02-04 KR KR1020227027228A patent/KR20220137652A/ko unknown
- 2021-02-04 IL IL295265A patent/IL295265A/en unknown
- 2021-02-04 WO PCT/US2021/016653 patent/WO2021158814A1/fr unknown
- 2021-02-04 EP EP21750337.4A patent/EP4081232A4/fr active Pending
- 2021-02-04 BR BR112022015345A patent/BR112022015345A2/pt unknown
- 2021-02-04 AU AU2021216405A patent/AU2021216405A1/en active Pending
- 2021-02-04 CA CA3166104A patent/CA3166104A1/fr active Pending
- 2021-02-04 JP JP2022547171A patent/JP2023513116A/ja active Pending
- 2021-02-04 CN CN202180013147.2A patent/CN116096391A/zh active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| WO2021158814A1 (fr) | 2021-08-12 |
| IL295265A (en) | 2022-10-01 |
| JP2023513116A (ja) | 2023-03-30 |
| EP4081232A1 (fr) | 2022-11-02 |
| CN116096391A (zh) | 2023-05-09 |
| EP4081232A4 (fr) | 2024-02-28 |
| KR20220137652A (ko) | 2022-10-12 |
| BR112022015345A2 (pt) | 2022-12-06 |
| WO2021158814A9 (fr) | 2022-09-01 |
| AU2021216405A1 (en) | 2022-09-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Zhang et al. | Cochlear gene therapy for sensorineural hearing loss: current status and major remaining hurdles for translational success | |
| US20200114023A1 (en) | Gene therapy constructs and methods for treatment of hearing loss | |
| Lalwani et al. | Long-term in vivo cochlear transgene expression mediated by recombinant adeno-associated virus | |
| JP7430652B2 (ja) | 蝸牛および前庭細胞に核酸を送達するための組成物および方法 | |
| Xue et al. | Gene editing in a Myo6 semi-dominant mouse model rescues auditory function | |
| Askew et al. | Adeno-associated virus gene replacement for recessive inner ear dysfunction: Progress and challenges | |
| Lee et al. | A null mutation of mouse Kcna10 causes significant vestibular and mild hearing dysfunction | |
| Lu et al. | Gene therapy with a synthetic adeno-associated viral vector improves audiovestibular phenotypes in Pjvk-mutant mice | |
| Liu et al. | Template-independent genome editing in the Pcdh15av− 3j mouse, a model of human DFNB23 nonsyndromic deafness | |
| Zhao et al. | Gene therapy restores auditory functions in an adult Vglut3 knockout mouse model | |
| US20220000972A1 (en) | A method for treating an auditory neuropathy spectrum disorder | |
| Schott et al. | Third-generation lentiviral gene therapy rescues function in a mouse model of Usher 1B | |
| US20200181596A1 (en) | Gene therapy systems and related methods for treatment of hearing loss | |
| CA3166104A1 (fr) | Systemes de therapie genique et methodes associees pour le traitement d'une perte de l'audition | |
| CN114369600B (zh) | 用于修复Klhl18lowf突变基因的CRISPR/Cas9基因编辑系统及应用 | |
| CN110099999B (zh) | 用于听力丧失综合征的动物模型及其治疗方法 | |
| Jin et al. | Genetic deafness and gene therapy approaches for treatment | |
| Hickham et al. | Tropism of novel AAV capsid variants in the inner ear | |
| CA3218213A1 (fr) | Constructions de therapie genique et procedes de traitement de la perte auditive | |
| Kim et al. | Development of genetic strategies to treat vision loss in Usher syndrome Type 1C (USH1C) | |
| Mendia et al. | Clarin-2 gene supplementation durably preserves hearing in a model of progressive hearing loss | |
| Lahlou et al. | Extended time frame for restoring inner ear function through gene therapy in Usher1G preclinical model | |
| Park SeoJin et al. | Attempted rescue of circling mice by hair cell-specific expression (Myo7a promoter) of tmie transgene. | |
| CN117157108A (zh) | 用于治疗clrn1相关听力损失和/或视力损失的组合物和方法 | |
| Shyng | Infantile Batten Disease: Effective Therapy and Novel Model |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20220927 |
|
| EEER | Examination request |
Effective date: 20220927 |
|
| EEER | Examination request |
Effective date: 20220927 |