AU2017281374A1 - Treatment of canavan disease - Google Patents
Treatment of canavan disease Download PDFInfo
- Publication number
- AU2017281374A1 AU2017281374A1 AU2017281374A AU2017281374A AU2017281374A1 AU 2017281374 A1 AU2017281374 A1 AU 2017281374A1 AU 2017281374 A AU2017281374 A AU 2017281374A AU 2017281374 A AU2017281374 A AU 2017281374A AU 2017281374 A1 AU2017281374 A1 AU 2017281374A1
- Authority
- AU
- Australia
- Prior art keywords
- cells
- aspa
- ipscs
- neural precursor
- wild type
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 208000022526 Canavan disease Diseases 0.000 title claims abstract description 257
- 210000004027 cell Anatomy 0.000 claims abstract description 198
- 210000005155 neural progenitor cell Anatomy 0.000 claims abstract description 182
- 230000001537 neural effect Effects 0.000 claims abstract description 111
- 239000002243 precursor Substances 0.000 claims abstract description 107
- 210000004556 brain Anatomy 0.000 claims abstract description 104
- 101150007902 ASPA gene Proteins 0.000 claims abstract description 74
- 238000000034 method Methods 0.000 claims abstract description 65
- 210000000130 stem cell Anatomy 0.000 claims abstract description 41
- 230000002255 enzymatic effect Effects 0.000 claims abstract description 30
- 230000002518 glial effect Effects 0.000 claims abstract description 18
- 230000008569 process Effects 0.000 claims abstract description 8
- 102100032948 Aspartoacylase Human genes 0.000 claims abstract 12
- 101000797251 Homo sapiens Aspartoacylase Proteins 0.000 claims abstract 12
- 210000004263 induced pluripotent stem cell Anatomy 0.000 claims description 212
- 230000008672 reprogramming Effects 0.000 claims description 48
- 210000001082 somatic cell Anatomy 0.000 claims description 43
- 210000002950 fibroblast Anatomy 0.000 claims description 27
- 230000035772 mutation Effects 0.000 claims description 22
- 238000010361 transduction Methods 0.000 claims description 19
- 230000026683 transduction Effects 0.000 claims description 19
- 238000005516 engineering process Methods 0.000 claims description 15
- 239000013598 vector Substances 0.000 claims description 15
- 102100024270 Transcription factor SOX-2 Human genes 0.000 claims description 13
- 230000003612 virological effect Effects 0.000 claims description 13
- 101000687905 Homo sapiens Transcription factor SOX-2 Proteins 0.000 claims description 12
- 101710126211 POU domain, class 5, transcription factor 1 Proteins 0.000 claims description 11
- 101001139134 Homo sapiens Krueppel-like factor 4 Proteins 0.000 claims description 9
- 101000984042 Homo sapiens Protein lin-28 homolog A Proteins 0.000 claims description 9
- 102100020677 Krueppel-like factor 4 Human genes 0.000 claims description 9
- 102100035423 POU domain, class 5, transcription factor 1 Human genes 0.000 claims description 9
- 102100025460 Protein lin-28 homolog A Human genes 0.000 claims description 9
- 210000001789 adipocyte Anatomy 0.000 claims description 7
- 210000000601 blood cell Anatomy 0.000 claims description 7
- 210000001968 dental pulp cell Anatomy 0.000 claims description 7
- 210000002510 keratinocyte Anatomy 0.000 claims description 7
- 230000002463 transducing effect Effects 0.000 claims description 7
- 230000002485 urinary effect Effects 0.000 claims description 7
- 241000713666 Lentivirus Species 0.000 claims description 6
- 238000010362 genome editing Methods 0.000 claims description 6
- 206010064571 Gene mutation Diseases 0.000 claims description 5
- 101001030211 Homo sapiens Myc proto-oncogene protein Proteins 0.000 claims description 5
- 102100038895 Myc proto-oncogene protein Human genes 0.000 claims description 5
- 102200132368 rs28940574 Human genes 0.000 claims description 4
- 102200045140 rs104894347 Human genes 0.000 claims description 2
- 241000699670 Mus sp. Species 0.000 description 138
- 108700023155 Aspartoacylases Proteins 0.000 description 137
- 102000018919 aspartoacylase Human genes 0.000 description 137
- 238000002054 transplantation Methods 0.000 description 47
- 241000699666 Mus <mouse, genus> Species 0.000 description 46
- 101150028585 Acy3 gene Proteins 0.000 description 40
- 102100032946 N-acyl-aromatic-L-amino acid amidohydrolase (carboxylate-forming) Human genes 0.000 description 40
- 102000019040 Nuclear Antigens Human genes 0.000 description 27
- 108010051791 Nuclear Antigens Proteins 0.000 description 27
- 239000002609 medium Substances 0.000 description 24
- 230000002441 reversible effect Effects 0.000 description 23
- OTCCIMWXFLJLIA-UHFFFAOYSA-N N-acetyl-DL-aspartic acid Natural products CC(=O)NC(C(O)=O)CC(O)=O OTCCIMWXFLJLIA-UHFFFAOYSA-N 0.000 description 22
- OTCCIMWXFLJLIA-BYPYZUCNSA-N N-acetyl-L-aspartic acid Chemical compound CC(=O)N[C@H](C(O)=O)CC(O)=O OTCCIMWXFLJLIA-BYPYZUCNSA-N 0.000 description 22
- 210000004248 oligodendroglia Anatomy 0.000 description 21
- 230000000694 effects Effects 0.000 description 19
- 230000002477 vacuolizing effect Effects 0.000 description 17
- 210000000133 brain stem Anatomy 0.000 description 16
- 230000014509 gene expression Effects 0.000 description 16
- 238000001415 gene therapy Methods 0.000 description 15
- 210000001638 cerebellum Anatomy 0.000 description 14
- 210000001103 thalamus Anatomy 0.000 description 14
- KISWVXRQTGLFGD-UHFFFAOYSA-N 2-[[2-[[6-amino-2-[[2-[[2-[[5-amino-2-[[2-[[1-[2-[[6-amino-2-[(2,5-diamino-5-oxopentanoyl)amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)p Chemical compound C1CCN(C(=O)C(CCCN=C(N)N)NC(=O)C(CCCCN)NC(=O)C(N)CCC(N)=O)C1C(=O)NC(CO)C(=O)NC(CCC(N)=O)C(=O)NC(CCCN=C(N)N)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 KISWVXRQTGLFGD-UHFFFAOYSA-N 0.000 description 13
- 206010028980 Neoplasm Diseases 0.000 description 13
- 201000010099 disease Diseases 0.000 description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 13
- 102000047918 Myelin Basic Human genes 0.000 description 12
- 101710107068 Myelin basic protein Proteins 0.000 description 12
- 238000010172 mouse model Methods 0.000 description 12
- 230000001575 pathological effect Effects 0.000 description 12
- 230000007659 motor function Effects 0.000 description 11
- 210000001519 tissue Anatomy 0.000 description 11
- 238000000692 Student's t-test Methods 0.000 description 10
- 238000002659 cell therapy Methods 0.000 description 10
- 210000001671 embryonic stem cell Anatomy 0.000 description 10
- 238000010186 staining Methods 0.000 description 10
- 102100039289 Glial fibrillary acidic protein Human genes 0.000 description 9
- 101710193519 Glial fibrillary acidic protein Proteins 0.000 description 9
- 206010043276 Teratoma Diseases 0.000 description 9
- 238000010171 animal model Methods 0.000 description 9
- 210000005046 glial fibrillary acidic protein Anatomy 0.000 description 9
- 230000003389 potentiating effect Effects 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 230000001225 therapeutic effect Effects 0.000 description 9
- 238000013459 approach Methods 0.000 description 8
- 108090000623 proteins and genes Proteins 0.000 description 8
- 238000011002 quantification Methods 0.000 description 8
- 241000283973 Oryctolagus cuniculus Species 0.000 description 7
- 229930040373 Paraformaldehyde Natural products 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 230000007850 degeneration Effects 0.000 description 7
- 210000005260 human cell Anatomy 0.000 description 7
- 238000012744 immunostaining Methods 0.000 description 7
- 229920002866 paraformaldehyde Polymers 0.000 description 7
- HJCMDXDYPOUFDY-WHFBIAKZSA-N Ala-Gln Chemical compound C[C@H](N)C(=O)N[C@H](C(O)=O)CCC(N)=O HJCMDXDYPOUFDY-WHFBIAKZSA-N 0.000 description 6
- 101100161959 Homo sapiens ASPA gene Proteins 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 230000007547 defect Effects 0.000 description 6
- 238000011161 development Methods 0.000 description 6
- 230000018109 developmental process Effects 0.000 description 6
- 230000004069 differentiation Effects 0.000 description 6
- 210000002242 embryoid body Anatomy 0.000 description 6
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 6
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 6
- 210000003007 myelin sheath Anatomy 0.000 description 6
- 239000002773 nucleotide Substances 0.000 description 6
- 125000003729 nucleotide group Chemical group 0.000 description 6
- 102200132384 rs28940279 Human genes 0.000 description 6
- 239000006228 supernatant Substances 0.000 description 6
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 5
- 101100193633 Danio rerio rag2 gene Proteins 0.000 description 5
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 101100193635 Mus musculus Rag2 gene Proteins 0.000 description 5
- 108091027967 Small hairpin RNA Proteins 0.000 description 5
- 241000700605 Viruses Species 0.000 description 5
- 230000007812 deficiency Effects 0.000 description 5
- 238000001493 electron microscopy Methods 0.000 description 5
- 210000001654 germ layer Anatomy 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 230000006698 induction Effects 0.000 description 5
- 239000003550 marker Substances 0.000 description 5
- 230000023105 myelination Effects 0.000 description 5
- 238000009256 replacement therapy Methods 0.000 description 5
- 238000003757 reverse transcription PCR Methods 0.000 description 5
- 238000010825 rotarod performance test Methods 0.000 description 5
- 239000004055 small Interfering RNA Substances 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 4
- 108091033409 CRISPR Proteins 0.000 description 4
- 108020004705 Codon Proteins 0.000 description 4
- 238000000116 DAPI staining Methods 0.000 description 4
- 101000721661 Homo sapiens Cellular tumor antigen p53 Proteins 0.000 description 4
- 102000008730 Nestin Human genes 0.000 description 4
- 108010088225 Nestin Proteins 0.000 description 4
- 238000010240 RT-PCR analysis Methods 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 238000012512 characterization method Methods 0.000 description 4
- 238000012937 correction Methods 0.000 description 4
- 230000002068 genetic effect Effects 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 239000013642 negative control Substances 0.000 description 4
- 210000005055 nestin Anatomy 0.000 description 4
- 210000001778 pluripotent stem cell Anatomy 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 230000005740 tumor formation Effects 0.000 description 4
- 238000010200 validation analysis Methods 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- AQGNHMOJWBZFQQ-UHFFFAOYSA-N CT 99021 Chemical compound CC1=CNC(C=2C(=NC(NCCNC=3N=CC(=CC=3)C#N)=NC=2)C=2C(=CC(Cl)=CC=2)Cl)=N1 AQGNHMOJWBZFQQ-UHFFFAOYSA-N 0.000 description 3
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 3
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 3
- 101000652332 Homo sapiens Transcription factor SOX-1 Proteins 0.000 description 3
- 102000004877 Insulin Human genes 0.000 description 3
- 108090001061 Insulin Proteins 0.000 description 3
- -1 L-Myc Proteins 0.000 description 3
- 102000006386 Myelin Proteins Human genes 0.000 description 3
- 108010083674 Myelin Proteins Proteins 0.000 description 3
- PKFBJSDMCRJYDC-GEZSXCAASA-N N-acetyl-s-geranylgeranyl-l-cysteine Chemical compound CC(C)=CCC\C(C)=C\CC\C(C)=C\CC\C(C)=C\CSC[C@@H](C(O)=O)NC(C)=O PKFBJSDMCRJYDC-GEZSXCAASA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- 101100247004 Rattus norvegicus Qsox1 gene Proteins 0.000 description 3
- 102100030248 Transcription factor SOX-1 Human genes 0.000 description 3
- 230000003542 behavioural effect Effects 0.000 description 3
- 239000007978 cacodylate buffer Substances 0.000 description 3
- 239000001110 calcium chloride Substances 0.000 description 3
- 229910001628 calcium chloride Inorganic materials 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 230000002950 deficient Effects 0.000 description 3
- 230000006735 deficit Effects 0.000 description 3
- 238000009795 derivation Methods 0.000 description 3
- 235000013922 glutamic acid Nutrition 0.000 description 3
- 239000004220 glutamic acid Substances 0.000 description 3
- 229940125396 insulin Drugs 0.000 description 3
- 238000011068 loading method Methods 0.000 description 3
- 108010082117 matrigel Proteins 0.000 description 3
- 210000005012 myelin Anatomy 0.000 description 3
- 230000002232 neuromuscular Effects 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 230000004580 weight loss Effects 0.000 description 3
- 102000007469 Actins Human genes 0.000 description 2
- 108010085238 Actins Proteins 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 238000010354 CRISPR gene editing Methods 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 238000001712 DNA sequencing Methods 0.000 description 2
- 101100518002 Danio rerio nkx2.2a gene Proteins 0.000 description 2
- 208000016192 Demyelinating disease Diseases 0.000 description 2
- 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 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 2
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 108700014808 Homeobox Protein Nkx-2.2 Proteins 0.000 description 2
- 102100027886 Homeobox protein Nkx-2.2 Human genes 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101000589632 Homo sapiens N-acetylaspartate synthetase Proteins 0.000 description 2
- 101100460496 Homo sapiens NKX2-2 gene Proteins 0.000 description 2
- 101000652324 Homo sapiens Transcription factor SOX-17 Proteins 0.000 description 2
- 108700021430 Kruppel-Like Factor 4 Proteins 0.000 description 2
- 102100032380 N-acetylaspartate synthetase Human genes 0.000 description 2
- 208000012902 Nervous system disease Diseases 0.000 description 2
- 208000025966 Neurological disease Diseases 0.000 description 2
- 108010032788 PAX6 Transcription Factor Proteins 0.000 description 2
- 102100037506 Paired box protein Pax-6 Human genes 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 102100030243 Transcription factor SOX-17 Human genes 0.000 description 2
- 102000004243 Tubulin Human genes 0.000 description 2
- 108090000704 Tubulin Proteins 0.000 description 2
- 108010076089 accutase Proteins 0.000 description 2
- 239000012574 advanced DMEM Substances 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 239000012131 assay buffer Substances 0.000 description 2
- 210000001130 astrocyte Anatomy 0.000 description 2
- 229960002685 biotin Drugs 0.000 description 2
- 235000020958 biotin Nutrition 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- 238000001369 bisulfite sequencing Methods 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 210000005013 brain tissue Anatomy 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000004624 confocal microscopy Methods 0.000 description 2
- 238000011109 contamination Methods 0.000 description 2
- 239000003599 detergent Substances 0.000 description 2
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 2
- 210000002304 esc Anatomy 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 2
- 238000003364 immunohistochemistry Methods 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 238000001462 microwave scanning near-field microscopy Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 239000012285 osmium tetroxide Substances 0.000 description 2
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 229940124598 therapeutic candidate Drugs 0.000 description 2
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 2
- 239000013603 viral vector Substances 0.000 description 2
- 210000004885 white matter Anatomy 0.000 description 2
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- HDXJBHKUPVMLDS-UHFFFAOYSA-L 2-aminobutanedioate;lead(2+) Chemical compound [Pb+2].[O-]C(=O)C(N)CC([O-])=O HDXJBHKUPVMLDS-UHFFFAOYSA-L 0.000 description 1
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 1
- CDOVNWNANFFLFJ-UHFFFAOYSA-N 4-[6-[4-(1-piperazinyl)phenyl]-3-pyrazolo[1,5-a]pyrimidinyl]quinoline Chemical compound C1CNCCN1C1=CC=C(C2=CN3N=CC(=C3N=C2)C=2C3=CC=CC=C3N=CC=2)C=C1 CDOVNWNANFFLFJ-UHFFFAOYSA-N 0.000 description 1
- 239000013607 AAV vector Substances 0.000 description 1
- 208000014825 Abnormal muscle tone Diseases 0.000 description 1
- 239000012103 Alexa Fluor 488 Substances 0.000 description 1
- 201000004569 Blindness Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 102000000905 Cadherin Human genes 0.000 description 1
- 108050007957 Cadherin Proteins 0.000 description 1
- 102100036364 Cadherin-2 Human genes 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 101100239628 Danio rerio myca gene Proteins 0.000 description 1
- 206010011878 Deafness Diseases 0.000 description 1
- 206010012305 Demyelination Diseases 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 101100118093 Drosophila melanogaster eEF1alpha2 gene Proteins 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 description 1
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 101000714537 Homo sapiens Cadherin-2 Proteins 0.000 description 1
- 101000979001 Homo sapiens Methionine aminopeptidase 2 Proteins 0.000 description 1
- 101000969087 Homo sapiens Microtubule-associated protein 2 Proteins 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 102000013460 Malate Dehydrogenase Human genes 0.000 description 1
- 108010026217 Malate Dehydrogenase Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- PKVZBNCYEICAQP-UHFFFAOYSA-N Mecamylamine hydrochloride Chemical compound Cl.C1CC2C(C)(C)C(NC)(C)C1C2 PKVZBNCYEICAQP-UHFFFAOYSA-N 0.000 description 1
- 208000036626 Mental retardation Diseases 0.000 description 1
- 102100023174 Methionine aminopeptidase 2 Human genes 0.000 description 1
- 101100137555 Mus musculus Prg2 gene Proteins 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- 108050000637 N-cadherin Proteins 0.000 description 1
- 101150012532 NANOG gene Proteins 0.000 description 1
- 108020004485 Nonsense Codon Proteins 0.000 description 1
- 101150085710 OCT4 gene Proteins 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 101150037203 Sox2 gene Proteins 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- LJTFFORYSFGNCT-UHFFFAOYSA-N Thiocarbohydrazide Chemical compound NNC(=S)NN LJTFFORYSFGNCT-UHFFFAOYSA-N 0.000 description 1
- 102000003929 Transaminases Human genes 0.000 description 1
- 108090000340 Transaminases Proteins 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- COQLPRJCUIATTQ-UHFFFAOYSA-N Uranyl acetate Chemical compound O.O.O=[U]=O.CC(O)=O.CC(O)=O COQLPRJCUIATTQ-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000035508 accumulation Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 101150063416 add gene Proteins 0.000 description 1
- 150000001294 alanine derivatives Chemical class 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 150000003862 amino acid derivatives Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 238000010805 cDNA synthesis kit Methods 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 239000002458 cell surface marker Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- PBAYDYUZOSNJGU-UHFFFAOYSA-N chelidonic acid Natural products OC(=O)C1=CC(=O)C=C(C(O)=O)O1 PBAYDYUZOSNJGU-UHFFFAOYSA-N 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000002559 cytogenic effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 229910003460 diamond Inorganic materials 0.000 description 1
- 239000010432 diamond Substances 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- XHBVYDAKJHETMP-UHFFFAOYSA-N dorsomorphin Chemical compound C=1C=C(C2=CN3N=CC(=C3N=C2)C=2C=CN=CC=2)C=CC=1OCCN1CCCCC1 XHBVYDAKJHETMP-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 239000004847 durcupan Substances 0.000 description 1
- 210000003981 ectoderm Anatomy 0.000 description 1
- 210000001705 ectoderm cell Anatomy 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 210000001900 endoderm Anatomy 0.000 description 1
- 238000007824 enzymatic assay Methods 0.000 description 1
- 238000001952 enzyme assay Methods 0.000 description 1
- 238000002641 enzyme replacement therapy Methods 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000000834 fixative Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 208000016361 genetic disease Diseases 0.000 description 1
- 125000000291 glutamic acid group Chemical class N[C@@H](CCC(O)=O)C(=O)* 0.000 description 1
- 235000013773 glyceryl triacetate Nutrition 0.000 description 1
- 239000001087 glyceryl triacetate Substances 0.000 description 1
- 150000002332 glycine derivatives Chemical class 0.000 description 1
- 230000010370 hearing loss Effects 0.000 description 1
- 231100000888 hearing loss Toxicity 0.000 description 1
- 208000016354 hearing loss disease Diseases 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 238000003365 immunocytochemistry Methods 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000013388 immunohistochemistry analysis Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 101150111214 lin-28 gene Proteins 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 210000003519 mature b lymphocyte Anatomy 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 210000003716 mesoderm Anatomy 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- 230000004973 motor coordination Effects 0.000 description 1
- 239000012120 mounting media Substances 0.000 description 1
- 210000004126 nerve fiber Anatomy 0.000 description 1
- 210000003061 neural cell Anatomy 0.000 description 1
- 210000001178 neural stem 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
- 230000037434 nonsense mutation Effects 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 108010017843 platelet-derived growth factor A Proteins 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000276 potassium ferrocyanide Substances 0.000 description 1
- YLMGFJXSLBMXHK-UHFFFAOYSA-M potassium perchlorate Chemical compound [K+].[O-]Cl(=O)(=O)=O YLMGFJXSLBMXHK-UHFFFAOYSA-M 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 229950010131 puromycin Drugs 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 239000011435 rock Substances 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000011272 standard treatment Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- XOGGUFAVLNCTRS-UHFFFAOYSA-N tetrapotassium;iron(2+);hexacyanide Chemical compound [K+].[K+].[K+].[K+].[Fe+2].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-] XOGGUFAVLNCTRS-UHFFFAOYSA-N 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000003151 transfection method Methods 0.000 description 1
- 238000004627 transmission electron microscopy Methods 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- PJHKBYALYHRYSK-UHFFFAOYSA-N triheptanoin Chemical compound CCCCCCC(=O)OCC(OC(=O)CCCCCC)COC(=O)CCCCCC PJHKBYALYHRYSK-UHFFFAOYSA-N 0.000 description 1
- 229940078561 triheptanoin Drugs 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 230000001228 trophic effect Effects 0.000 description 1
- 238000003260 vortexing Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/30—Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue
-
- 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
-
- 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
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0618—Cells of the nervous system
- C12N5/0623—Stem cells
-
- 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
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0696—Artificially induced pluripotent stem cells, e.g. iPS
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/07—Animals genetically altered by homologous recombination
- A01K2217/075—Animals genetically altered by homologous recombination inducing loss of function, i.e. knock out
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2227/00—Animals characterised by species
- A01K2227/10—Mammal
- A01K2227/105—Murine
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
- A01K2267/0306—Animal model for genetic diseases
- A01K2267/0318—Animal model for neurodegenerative disease, e.g. non- Alzheimer's
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/60—Transcription factors
- C12N2501/602—Sox-2
-
- 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
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/60—Transcription factors
- C12N2501/603—Oct-3/4
-
- 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
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/60—Transcription factors
- C12N2501/604—Klf-4
-
- 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
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/60—Transcription factors
- C12N2501/606—Transcription factors c-Myc
-
- 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
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/60—Transcription factors
- C12N2501/608—Lin28
-
- 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
- C12N2506/00—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells
- C12N2506/13—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from connective tissue cells, from mesenchymal cells
- C12N2506/1307—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from connective tissue cells, from mesenchymal cells from adult fibroblasts
-
- 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
- C12N2506/00—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells
- C12N2506/45—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from artificially induced pluripotent stem cells
-
- 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
- C12N2510/00—Genetically modified cells
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/16011—Human Immunodeficiency Virus, HIV
- C12N2740/16041—Use of virus, viral particle or viral elements as a vector
- C12N2740/16043—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)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Biotechnology (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Cell Biology (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Developmental Biology & Embryology (AREA)
- General Health & Medical Sciences (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- General Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Virology (AREA)
- Ophthalmology & Optometry (AREA)
- Immunology (AREA)
- Transplantation (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Enzymes And Modification Thereof (AREA)
- Materials For Medical Uses (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662353515P | 2016-06-22 | 2016-06-22 | |
| US62/353,515 | 2016-06-22 | ||
| PCT/US2017/038853 WO2017223373A1 (en) | 2016-06-22 | 2017-06-22 | Treatment of canavan disease |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2017281374A1 true AU2017281374A1 (en) | 2019-01-03 |
Family
ID=60784859
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2017281374A Abandoned AU2017281374A1 (en) | 2016-06-22 | 2017-06-22 | Treatment of canavan disease |
Country Status (7)
| Country | Link |
|---|---|
| US (2) | US20190307808A1 (https=) |
| EP (1) | EP3474876A4 (https=) |
| JP (2) | JP2019518775A (https=) |
| CN (1) | CN110035764B (https=) |
| AU (1) | AU2017281374A1 (https=) |
| CA (1) | CA3028714A1 (https=) |
| WO (1) | WO2017223373A1 (https=) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2022076206A1 (en) * | 2020-10-05 | 2022-04-14 | City Of Hope | Treatment of canavan disease |
| CN117999363A (zh) * | 2021-08-17 | 2024-05-07 | 希望之城 | 用于无细胞的dna表观遗传的胃肠道癌检测以及治疗的组成物和方法 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2172963C (en) * | 1993-09-29 | 2007-09-11 | Reuben Matalon | Aspartoacylase gene, protein, and methods of screening for mutations associated with canavan disease |
| WO2013120497A1 (en) * | 2012-02-15 | 2013-08-22 | Curevac Gmbh | Nucleic acid comprising or coding for a histone stem-loop and a poly(a) sequence or a polyadenylation signal for increasing the expression of an encoded therapeutic protein |
| PL2861733T3 (pl) * | 2012-05-30 | 2021-04-19 | Rowan University | Terapia metaboliczna stresu oksydacyjnego w mózgu przez ukierunkowany neuronalny katabolizm kwasu n-acetyloasparaginowego |
| JP6541577B2 (ja) * | 2013-02-06 | 2019-07-10 | ユニバーシティー オブ ロチェスター | ミエリン障害の治療のための誘導多能性細胞由来オリゴデンドロサイト前駆細胞 |
| WO2015153760A2 (en) * | 2014-04-01 | 2015-10-08 | Sangamo Biosciences, Inc. | Methods and compositions for prevention or treatment of a nervous system disorder |
| WO2015188056A1 (en) * | 2014-06-05 | 2015-12-10 | Sangamo Biosciences, Inc. | Methods and compositions for nuclease design |
-
2017
- 2017-06-22 CN CN201780051943.9A patent/CN110035764B/zh not_active Expired - Fee Related
- 2017-06-22 EP EP17816246.7A patent/EP3474876A4/en not_active Withdrawn
- 2017-06-22 CA CA3028714A patent/CA3028714A1/en active Pending
- 2017-06-22 US US16/311,995 patent/US20190307808A1/en not_active Abandoned
- 2017-06-22 AU AU2017281374A patent/AU2017281374A1/en not_active Abandoned
- 2017-06-22 JP JP2018567237A patent/JP2019518775A/ja active Pending
- 2017-06-22 WO PCT/US2017/038853 patent/WO2017223373A1/en not_active Ceased
-
2022
- 2022-12-15 JP JP2022199966A patent/JP2023029376A/ja active Pending
-
2023
- 2023-10-17 US US18/488,859 patent/US20240197789A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| US20190307808A1 (en) | 2019-10-10 |
| WO2017223373A1 (en) | 2017-12-28 |
| JP2023029376A (ja) | 2023-03-03 |
| CA3028714A1 (en) | 2017-12-28 |
| EP3474876A4 (en) | 2020-01-15 |
| EP3474876A1 (en) | 2019-05-01 |
| JP2019518775A (ja) | 2019-07-04 |
| CN110035764B (zh) | 2023-08-15 |
| US20240197789A1 (en) | 2024-06-20 |
| CN110035764A (zh) | 2019-07-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7277978B2 (ja) | ミエリン障害の治療のための誘導多能性細胞由来オリゴデンドロサイト前駆細胞 | |
| Rubio et al. | Genetically perpetuated human neural stem cells engraft and differentiate into the adult mammalian brain | |
| Kennea et al. | Differentiation of human fetal mesenchymal stem cells into cells with an oligodendrocyte phenotype | |
| US20240197789A1 (en) | Treatment of canavan disease | |
| CA2852593A1 (en) | Methods for producing dopaminergic neurons and uses thereof | |
| JP6342115B2 (ja) | 再プログラム化多能性細胞の作製 | |
| US20180051259A1 (en) | Cell fate conversion of differentiated somatic cells into glial cells | |
| Mozafari et al. | Skin-derived neural precursors competitively generate functional myelin in adult demyelinated mice | |
| Feng et al. | Cell‐based therapy for canavan disease using human iPSC‐derived NPCs and OPCs | |
| Feng et al. | Developing hypoimmunogenic human iPSC‐derived oligodendrocyte progenitor cells as an off‐the‐shelf cell therapy for myelin disorders | |
| JP2024074958A (ja) | 合成メッセンジャーｒｎａを用いて尿細胞を神経幹細胞へ直接逆分化する方法 | |
| Kim et al. | Generation of human myogenic progenitors from pluripotent stem cells for in vivo regeneration | |
| Beatriz et al. | Revisiting cell and gene therapies in Huntington’s disease | |
| US20240254440A1 (en) | Methods to generate glial restricted neural progenitor cells and uses thereof | |
| Liu et al. | Pluripotent fates and tissue regenerative potential of adult olfactory bulb neural stem and progenitor cells | |
| US20170360841A1 (en) | Methods for producing dopaminergic neurons and uses thereof | |
| US20230416689A1 (en) | Treatment of canavan disease | |
| Wenceslau et al. | Pluripotent stem cells to model and treat huntington’s disease | |
| Reymann | Neuronal differentiation of human iPS-cells in a rat cortical primary culture | |
| Al-maqtari | Approaches in the treatment of Parkinson's disease: a focus on stem cell-based therapies | |
| Bonaventura et al. | Induced pluripotent stem cells: an innovative patient-specific neurodegenerative disease modeling | |
| Heine et al. | Induced Pluripotent Stem Cells in Brain Diseases: Understanding the Methods, Epigenetic Basis, and Applications for Regenerative Medicine. | |
| Martino et al. | Skin-derived neural precursors competitively generate functional myelin in adult demyelinated mice | |
| Griffin | Ex vivo gene therapy for lysosomal storage disease using IPSC-derived neural stem cells | |
| Eren et al. | Induced Pluripotent Stem Cell Therapy and Safety Concerns in Age-Related Chronic Neurodegenerative Diseases |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK4 | Application lapsed section 142(2)(d) - no continuation fee paid for the application |