CA2146929A1 - Transfert via un processus retroviral d'un gene humain polypharmacoresistant - Google Patents
Transfert via un processus retroviral d'un gene humain polypharmacoresistantInfo
- Publication number
- CA2146929A1 CA2146929A1 CA002146929A CA2146929A CA2146929A1 CA 2146929 A1 CA2146929 A1 CA 2146929A1 CA 002146929 A CA002146929 A CA 002146929A CA 2146929 A CA2146929 A CA 2146929A CA 2146929 A1 CA2146929 A1 CA 2146929A1
- Authority
- CA
- Canada
- Prior art keywords
- mdr
- cells
- gene
- retroviral
- cell
- 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
- 230000001177 retroviral effect Effects 0.000 title claims abstract description 148
- 108090000623 proteins and genes Proteins 0.000 title claims abstract description 120
- 241000282414 Homo sapiens Species 0.000 title claims abstract description 72
- 206010048723 Multiple-drug resistance Diseases 0.000 title claims abstract description 17
- 238000012546 transfer Methods 0.000 title description 22
- 230000001404 mediated effect Effects 0.000 title description 5
- 210000004027 cell Anatomy 0.000 claims abstract description 330
- 229940079593 drug Drugs 0.000 claims abstract description 80
- 239000003814 drug Substances 0.000 claims abstract description 80
- 241000124008 Mammalia Species 0.000 claims abstract description 71
- 108700041567 MDR Genes Proteins 0.000 claims abstract description 70
- 238000000034 method Methods 0.000 claims abstract description 63
- 230000014509 gene expression Effects 0.000 claims abstract description 52
- 238000004806 packaging method and process Methods 0.000 claims abstract description 48
- 239000013598 vector Substances 0.000 claims abstract description 43
- 239000002245 particle Substances 0.000 claims abstract description 38
- 210000004962 mammalian cell Anatomy 0.000 claims abstract description 33
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 21
- 201000011510 cancer Diseases 0.000 claims abstract description 17
- 230000002463 transducing effect Effects 0.000 claims abstract description 17
- 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 claims abstract description 14
- 108090001061 Insulin Proteins 0.000 claims abstract description 8
- 230000002159 abnormal effect Effects 0.000 claims abstract description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 8
- 208000035475 disorder Diseases 0.000 claims abstract description 8
- 102000004877 Insulin Human genes 0.000 claims abstract description 7
- 229940125396 insulin Drugs 0.000 claims abstract description 7
- IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 claims description 114
- 229960001338 colchicine Drugs 0.000 claims description 57
- 231100000433 cytotoxic Toxicity 0.000 claims description 24
- 230000001472 cytotoxic effect Effects 0.000 claims description 24
- 241001465754 Metazoa Species 0.000 claims description 15
- 238000010361 transduction Methods 0.000 claims description 15
- 230000026683 transduction Effects 0.000 claims description 15
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 229930012538 Paclitaxel Natural products 0.000 claims description 9
- 229960001592 paclitaxel Drugs 0.000 claims description 9
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims description 9
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 8
- 229940045799 anthracyclines and related substance Drugs 0.000 claims description 8
- 210000004881 tumor cell Anatomy 0.000 claims description 8
- 229940122803 Vinca alkaloid Drugs 0.000 claims description 7
- 210000004698 lymphocyte Anatomy 0.000 claims description 6
- 238000012258 culturing Methods 0.000 claims description 5
- 210000000988 bone and bone Anatomy 0.000 claims description 3
- 206010025323 Lymphomas Diseases 0.000 claims description 2
- 206010039491 Sarcoma Diseases 0.000 claims description 2
- 208000002903 Thalassemia Diseases 0.000 claims description 2
- 206010012601 diabetes mellitus Diseases 0.000 claims description 2
- 208000032839 leukemia Diseases 0.000 claims description 2
- 208000007502 anemia Diseases 0.000 claims 1
- 108700026220 vif Genes Proteins 0.000 claims 1
- 241001430294 unidentified retrovirus Species 0.000 abstract description 24
- 210000002798 bone marrow cell Anatomy 0.000 description 37
- 108020004414 DNA Proteins 0.000 description 34
- 239000006228 supernatant Substances 0.000 description 29
- 241000699666 Mus <mouse, genus> Species 0.000 description 26
- 238000002474 experimental method Methods 0.000 description 22
- 238000003752 polymerase chain reaction Methods 0.000 description 21
- 241000699670 Mus sp. Species 0.000 description 19
- 238000003556 assay Methods 0.000 description 18
- 210000001185 bone marrow Anatomy 0.000 description 18
- 108090000288 Glycoproteins Proteins 0.000 description 16
- 102000003886 Glycoproteins Human genes 0.000 description 16
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 16
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 16
- 238000012360 testing method Methods 0.000 description 16
- 239000002299 complementary DNA Substances 0.000 description 14
- 108020004999 messenger RNA Proteins 0.000 description 13
- 238000002105 Southern blotting Methods 0.000 description 12
- 241000700605 Viruses Species 0.000 description 12
- 239000013612 plasmid Substances 0.000 description 12
- 239000013641 positive control Substances 0.000 description 12
- 230000003612 virological effect Effects 0.000 description 12
- 239000000047 product Substances 0.000 description 11
- 241001529936 Murinae Species 0.000 description 10
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 10
- 239000013642 negative control Substances 0.000 description 10
- 150000007523 nucleic acids Chemical group 0.000 description 10
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 9
- 102100033350 ATP-dependent translocase ABCB1 Human genes 0.000 description 9
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 9
- 108010047230 Member 1 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 9
- 230000010354 integration Effects 0.000 description 9
- 210000000130 stem cell Anatomy 0.000 description 9
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 8
- 241001364944 Mus terricolor Species 0.000 description 8
- 239000012894 fetal calf serum Substances 0.000 description 8
- 101100422770 Caenorhabditis elegans sup-1 gene Proteins 0.000 description 7
- 230000001419 dependent effect Effects 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 238000000338 in vitro Methods 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- 239000003550 marker Substances 0.000 description 7
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- 238000010222 PCR analysis Methods 0.000 description 6
- 239000000499 gel Substances 0.000 description 6
- 238000003780 insertion Methods 0.000 description 6
- 230000037431 insertion Effects 0.000 description 6
- 230000002906 microbiologic effect Effects 0.000 description 6
- 210000000952 spleen Anatomy 0.000 description 6
- 108020005544 Antisense RNA Proteins 0.000 description 5
- 241000282324 Felis Species 0.000 description 5
- 239000003184 complementary RNA Substances 0.000 description 5
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 5
- 210000002381 plasma Anatomy 0.000 description 5
- 231100000331 toxic Toxicity 0.000 description 5
- 230000002588 toxic effect Effects 0.000 description 5
- 238000013519 translation Methods 0.000 description 5
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
- 229920000209 Hexadimethrine bromide Polymers 0.000 description 4
- 241000699660 Mus musculus Species 0.000 description 4
- 238000000636 Northern blotting Methods 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- 230000003321 amplification Effects 0.000 description 4
- 239000002246 antineoplastic agent Substances 0.000 description 4
- 238000010322 bone marrow transplantation Methods 0.000 description 4
- AIYUHDOJVYHVIT-UHFFFAOYSA-M caesium chloride Chemical compound [Cl-].[Cs+] AIYUHDOJVYHVIT-UHFFFAOYSA-M 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000002512 chemotherapy Methods 0.000 description 4
- 229940127089 cytotoxic agent Drugs 0.000 description 4
- 210000000265 leukocyte Anatomy 0.000 description 4
- 230000007774 longterm Effects 0.000 description 4
- 238000003199 nucleic acid amplification method Methods 0.000 description 4
- 108020004707 nucleic acids Proteins 0.000 description 4
- 102000039446 nucleic acids Human genes 0.000 description 4
- 210000005259 peripheral blood Anatomy 0.000 description 4
- 239000011886 peripheral blood Substances 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 238000011830 transgenic mouse model Methods 0.000 description 4
- 238000002054 transplantation Methods 0.000 description 4
- 238000011282 treatment Methods 0.000 description 4
- 210000000689 upper leg Anatomy 0.000 description 4
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEAHRLBPCANXCN-UHFFFAOYSA-N Daunomycin Natural products CCC1(O)CC(OC2CC(N)C(O)C(C)O2)c3cc4C(=O)c5c(OC)cccc5C(=O)c4c(O)c3C1 WEAHRLBPCANXCN-UHFFFAOYSA-N 0.000 description 3
- 108010067770 Endopeptidase K Proteins 0.000 description 3
- 101000899111 Homo sapiens Hemoglobin subunit beta Proteins 0.000 description 3
- 108090001005 Interleukin-6 Proteins 0.000 description 3
- 210000002960 bfu-e Anatomy 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 238000003501 co-culture Methods 0.000 description 3
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 230000029087 digestion Effects 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 210000003743 erythrocyte Anatomy 0.000 description 3
- 210000003714 granulocyte Anatomy 0.000 description 3
- 239000003102 growth factor Substances 0.000 description 3
- 239000006166 lysate Substances 0.000 description 3
- 230000002018 overexpression Effects 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 210000003462 vein Anatomy 0.000 description 3
- 238000011746 C57BL/6J (JAX™ mouse strain) Methods 0.000 description 2
- 230000004544 DNA amplification Effects 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 108700024394 Exon Proteins 0.000 description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
- 108010002350 Interleukin-2 Proteins 0.000 description 2
- 108010002386 Interleukin-3 Proteins 0.000 description 2
- 239000007993 MOPS buffer Substances 0.000 description 2
- 240000000233 Melia azedarach Species 0.000 description 2
- 241000713869 Moloney murine leukemia virus Species 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 241000053227 Themus Species 0.000 description 2
- 238000000137 annealing Methods 0.000 description 2
- 238000004820 blood count Methods 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000004925 denaturation Methods 0.000 description 2
- 230000036425 denaturation Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 210000000267 erythroid cell Anatomy 0.000 description 2
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 2
- 229960005542 ethidium bromide Drugs 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 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 2
- 238000011010 flushing procedure Methods 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 201000001441 melanoma Diseases 0.000 description 2
- 230000036457 multidrug resistance Effects 0.000 description 2
- 208000007056 sickle cell anemia Diseases 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 210000002303 tibia Anatomy 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- -1 anthracyclines Chemical compound 0.000 description 1
- YJEKMTAQATUVNH-UHFFFAOYSA-N 3,7-dihydropurine-2,6-dione;3,7-dihydropurin-6-one Chemical compound O=C1NC=NC2=C1NC=N2.O=C1NC(=O)NC2=C1NC=N2 YJEKMTAQATUVNH-UHFFFAOYSA-N 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 241001128034 Amphotropic murine leukemia virus Species 0.000 description 1
- 208000019838 Blood disease Diseases 0.000 description 1
- 102100032528 C-type lectin domain family 11 member A Human genes 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 102100035360 Cerebellar degeneration-related antigen 1 Human genes 0.000 description 1
- 241000219122 Cucurbita Species 0.000 description 1
- 235000009804 Cucurbita pepo subsp pepo Nutrition 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 102100031780 Endonuclease Human genes 0.000 description 1
- 208000031637 Erythroblastic Acute Leukemia Diseases 0.000 description 1
- 208000036566 Erythroleukaemia Diseases 0.000 description 1
- 102100027286 Fanconi anemia group C protein Human genes 0.000 description 1
- 241000714165 Feline leukemia virus Species 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 210000000712 G cell Anatomy 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000942297 Homo sapiens C-type lectin domain family 11 member A Proteins 0.000 description 1
- 101000737793 Homo sapiens Cerebellar degeneration-related antigen 1 Proteins 0.000 description 1
- 101000716729 Homo sapiens Kit ligand Proteins 0.000 description 1
- 101150101999 IL6 gene Proteins 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 101710177504 Kit ligand Proteins 0.000 description 1
- 241000714178 Mink cell focus-forming virus Species 0.000 description 1
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 108091006629 SLC13A2 Proteins 0.000 description 1
- 108091081021 Sense strand Proteins 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 206010043391 Thalassaemia beta Diseases 0.000 description 1
- 206010043395 Thalassaemia sickle cell Diseases 0.000 description 1
- 241000656145 Thyrsites atun Species 0.000 description 1
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 208000021841 acute erythroid leukemia Diseases 0.000 description 1
- 101150027964 ada gene Proteins 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 208000005980 beta thalassemia Diseases 0.000 description 1
- 208000022806 beta-thalassemia major Diseases 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 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
- 244000309466 calf Species 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 239000013611 chromosomal DNA Substances 0.000 description 1
- 238000000975 co-precipitation Methods 0.000 description 1
- 230000001332 colony forming effect Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000003636 conditioned culture medium Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
- 238000011037 discontinuous sequential dilution Methods 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 108700004025 env Genes Proteins 0.000 description 1
- 101150030339 env gene Proteins 0.000 description 1
- 229960005420 etoposide Drugs 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 108010027225 gag-pol Fusion Proteins Proteins 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 208000016361 genetic disease Diseases 0.000 description 1
- 238000011773 genetically engineered mouse model Methods 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000014951 hematologic disease Diseases 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 208000018706 hematopoietic system disease Diseases 0.000 description 1
- 102000055151 human KITLG Human genes 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 210000002414 leg Anatomy 0.000 description 1
- 201000002364 leukopenia Diseases 0.000 description 1
- 231100001022 leukopenia Toxicity 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 108700039855 mouse a Proteins 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- XEBWQGVWTUSTLN-UHFFFAOYSA-M phenylmercury acetate Chemical compound CC(=O)O[Hg]C1=CC=CC=C1 XEBWQGVWTUSTLN-UHFFFAOYSA-M 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 101150038105 pr gene Proteins 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000001566 pro-viral effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000004853 protein function Effects 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 238000002976 reverse transcriptase assay Methods 0.000 description 1
- 239000012146 running buffer Substances 0.000 description 1
- 231100000279 safety data Toxicity 0.000 description 1
- 238000009781 safety test method Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000012898 sample dilution Substances 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 231100000041 toxicology testing Toxicity 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000009261 transgenic effect Effects 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
- 229960001005 tuberculin Drugs 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 238000010451 viral insertion Methods 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 239000002676 xenobiotic agent Substances 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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/475—Quinolines; Isoquinolines having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- 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
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- 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
- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/13011—Gammaretrovirus, e.g. murine leukeamia virus
- C12N2740/13041—Use of virus, viral particle or viral elements as a vector
- C12N2740/13043—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)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Biophysics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Diabetes (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Toxicology (AREA)
- Emergency Medicine (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Virology (AREA)
- Physics & Mathematics (AREA)
- Endocrinology (AREA)
- Cell Biology (AREA)
- Gastroenterology & Hepatology (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Immunology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US96247492A | 1992-10-16 | 1992-10-16 | |
| US07/962,474 | 1992-10-16 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2146929A1 true CA2146929A1 (fr) | 1994-04-28 |
Family
ID=25505916
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002146929A Abandoned CA2146929A1 (fr) | 1992-10-16 | 1993-10-15 | Transfert via un processus retroviral d'un gene humain polypharmacoresistant |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP0672119A4 (fr) |
| JP (1) | JPH08506719A (fr) |
| AU (1) | AU687765B2 (fr) |
| CA (1) | CA2146929A1 (fr) |
| WO (1) | WO1994009120A1 (fr) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2135645A1 (fr) * | 1992-05-22 | 1993-12-09 | Genetic Therapy, Inc. | Expression amelioree de genes humains de resistance a plusieurs medicaments et selection amelioree des cellules transduites avec lesdits genes |
| EP0781343B1 (fr) * | 1994-09-08 | 2003-07-02 | Vision 7 GmbH | Hybrides vectoriels retroviraux et leur utilisation pour le transfert de genes |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6333612A (ja) * | 1986-07-29 | 1988-02-13 | Toshiba Corp | 光フアイバジヤイロ |
| JPS63300906A (ja) * | 1987-06-01 | 1988-12-08 | Tokyo Keiki Co Ltd | 光ファイバ回転角速度計 |
| JPH0690037B2 (ja) * | 1988-06-03 | 1994-11-14 | 日本航空電子工業株式会社 | 光ファイバコイル |
| JPH0755434Y2 (ja) * | 1989-08-30 | 1995-12-20 | カルソニック株式会社 | パイプの接続構造 |
| CA2135645A1 (fr) * | 1992-05-22 | 1993-12-09 | Genetic Therapy, Inc. | Expression amelioree de genes humains de resistance a plusieurs medicaments et selection amelioree des cellules transduites avec lesdits genes |
-
1993
- 1993-10-15 JP JP6510348A patent/JPH08506719A/ja not_active Expired - Lifetime
- 1993-10-15 EP EP93924952A patent/EP0672119A4/fr not_active Withdrawn
- 1993-10-15 AU AU54445/94A patent/AU687765B2/en not_active Expired
- 1993-10-15 WO PCT/US1993/009988 patent/WO1994009120A1/fr not_active Application Discontinuation
- 1993-10-15 CA CA002146929A patent/CA2146929A1/fr not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| AU5444594A (en) | 1994-05-09 |
| WO1994009120A1 (fr) | 1994-04-28 |
| AU687765B2 (en) | 1998-03-05 |
| JPH08506719A (ja) | 1996-07-23 |
| EP0672119A1 (fr) | 1995-09-20 |
| EP0672119A4 (fr) | 1997-06-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Mosca et al. | Mesenchymal stem cells as vehicles for gene delivery. | |
| Donahue et al. | Helper virus induced T cell lymphoma in nonhuman primates after retroviral mediated gene transfer. | |
| Rosenzweig et al. | Induction of cytotoxic T lymphocyte and antibody responses to enhanced green fluorescent protein following transplantation of transduced CD34+ hematopoietic cells | |
| US5928638A (en) | Methods for gene transfer | |
| Eckert et al. | High-dose multidrug resistance in primary human hematopoietic progenitor cells transduced with optimized retroviral vectors | |
| US20150224209A1 (en) | Lentiviral vector for stem cell gene therapy of sickle cell disease | |
| JP2003501482A (ja) | 移植片対宿主疾患の処置のためのｃｄ２０に対する抗体の使用 | |
| JPH07505045A (ja) | 移植における特異的寛容 | |
| JP2001169789A (ja) | ウイルス仲介ｄｎａ導入の増強 | |
| Havenga et al. | Retroviral stem cell gene therapy | |
| JPH10507905A (ja) | ヒト血清による溶解耐性生産者細胞系で生産されるレトロウイルスベクター | |
| WO1995034639A1 (fr) | Nouvelle enveloppe retrovirale et long segment terminal a repetitions (ltr) et particules de vecteur retroviral comprenant cette enveloppe et/ou le ltr | |
| DelaFlor-Weiss et al. | Transfer and expression of the human multidrug resistance gene in mouse erythroleukemia cells | |
| US6090608A (en) | SV-40 derived DNA constructs comprising exogenous DNA sequences | |
| NZ300795A (en) | Retroviral Plasmid Vectors (enhancer region of LTR replaced, primer binding site replaced or mutated), packaging/transduced cells, use for gene therapy | |
| AU687765B2 (en) | Retroviral mediated transfer of the human multiple drug resistance gene | |
| US6022738A (en) | Vectors for expression of globin genes | |
| CN115947865A (zh) | 一种嵌合抗原受体、表达构建物、car-t细胞及其应用 | |
| Shafer et al. | Expression of a swine class II gene in murine bone marrow hematopoietic cells by retroviral-mediated gene transfer. | |
| EP1521839B1 (fr) | Methodes permettant d'obtenir des particules presentant une activite de liaison cellulaire modifiee et utilisations correspondantes | |
| Peters et al. | Retrovirus mediated gene transfer of the self antigen MBP into the bone marrow of mice alters resistance to experimental autoimmune encephalomyelitis | |
| WO2001066150A2 (fr) | Transfert genique a efficacite elevee dans des cellules souches humaines de repopulation a l'aide de particules de vecteur retroviral pseudotype rd114 | |
| Bank et al. | Transfer of the MDR-1 gene into hematopoietic cells | |
| JP2003500050A (ja) | 改善されたベクターの選択方法 | |
| Bertolini et al. | Gene transfer-mediated generation of drug-resistant hemopoiesis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Dead |