AU708658B2 - Methods and compounds for curing diseases caused by mutations - Google Patents
Methods and compounds for curing diseases caused by mutations Download PDFInfo
- Publication number
- AU708658B2 AU708658B2 AU28225/97A AU2822597A AU708658B2 AU 708658 B2 AU708658 B2 AU 708658B2 AU 28225/97 A AU28225/97 A AU 28225/97A AU 2822597 A AU2822597 A AU 2822597A AU 708658 B2 AU708658 B2 AU 708658B2
- Authority
- AU
- Australia
- Prior art keywords
- seq
- nucleic acid
- sequence
- region
- dna
- 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.)
- Ceased
Links
- 230000035772 mutation Effects 0.000 title claims description 108
- 238000000034 method Methods 0.000 title claims description 35
- 201000010099 disease Diseases 0.000 title claims description 23
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims description 23
- 150000001875 compounds Chemical class 0.000 title description 5
- 108020004707 nucleic acids Proteins 0.000 claims description 121
- 102000039446 nucleic acids Human genes 0.000 claims description 121
- 150000007523 nucleic acids Chemical class 0.000 claims description 121
- 210000004027 cell Anatomy 0.000 claims description 114
- 108090000623 proteins and genes Proteins 0.000 claims description 79
- 239000002773 nucleotide Substances 0.000 claims description 50
- 125000003729 nucleotide group Chemical group 0.000 claims description 50
- 239000012634 fragment Substances 0.000 claims description 46
- 239000002336 ribonucleotide Substances 0.000 claims description 34
- 108091028664 Ribonucleotide Proteins 0.000 claims description 33
- 125000002652 ribonucleotide group Chemical group 0.000 claims description 33
- 210000003958 hematopoietic stem cell Anatomy 0.000 claims description 29
- 108700028369 Alleles Proteins 0.000 claims description 23
- 108020004774 Alkaline Phosphatase Proteins 0.000 claims description 14
- 239000005547 deoxyribonucleotide Substances 0.000 claims description 13
- 108010017544 Glucosylceramidase Proteins 0.000 claims description 12
- 101800002712 p27 Proteins 0.000 claims description 12
- 102000002260 Alkaline Phosphatase Human genes 0.000 claims description 10
- 108020004414 DNA Proteins 0.000 description 143
- 108091034117 Oligonucleotide Proteins 0.000 description 52
- 230000008439 repair process Effects 0.000 description 34
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 19
- 238000006243 chemical reaction Methods 0.000 description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- 238000001890 transfection Methods 0.000 description 18
- 208000015872 Gaucher disease Diseases 0.000 description 17
- 108091033380 Coding strand Proteins 0.000 description 16
- 208000002903 Thalassemia Diseases 0.000 description 15
- 108020004705 Codon Proteins 0.000 description 13
- 239000000523 sample Substances 0.000 description 13
- 210000001185 bone marrow Anatomy 0.000 description 12
- 239000013612 plasmid Substances 0.000 description 12
- 238000012937 correction Methods 0.000 description 11
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 10
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 10
- 208000007056 sickle cell anemia Diseases 0.000 description 10
- 239000013598 vector Substances 0.000 description 10
- 238000001712 DNA sequencing Methods 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 9
- 238000010322 bone marrow transplantation Methods 0.000 description 9
- 239000000499 gel Substances 0.000 description 9
- 238000009396 hybridization Methods 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- 238000006467 substitution reaction Methods 0.000 description 9
- 102000004547 Glucosylceramidase Human genes 0.000 description 8
- 108091028043 Nucleic acid sequence Proteins 0.000 description 8
- 238000012217 deletion Methods 0.000 description 8
- 230000037430 deletion Effects 0.000 description 8
- 239000012091 fetal bovine serum Substances 0.000 description 8
- 108060003196 globin Proteins 0.000 description 8
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- KSXTUUUQYQYKCR-LQDDAWAPSA-M 2,3-bis[[(z)-octadec-9-enoyl]oxy]propyl-trimethylazanium;chloride Chemical compound [Cl-].CCCCCCCC\C=C/CCCCCCCC(=O)OCC(C[N+](C)(C)C)OC(=O)CCCCCCC\C=C/CCCCCCCC KSXTUUUQYQYKCR-LQDDAWAPSA-M 0.000 description 7
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 7
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 7
- -1 e.g. Proteins 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 238000003780 insertion Methods 0.000 description 7
- 230000037431 insertion Effects 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 238000010186 staining Methods 0.000 description 7
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 6
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 6
- 230000002255 enzymatic effect Effects 0.000 description 6
- 230000001744 histochemical effect Effects 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 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 5
- 101150040459 RAS gene Proteins 0.000 description 5
- HMNZFMSWFCAGGW-XPWSMXQVSA-N [3-[hydroxy(2-hydroxyethoxy)phosphoryl]oxy-2-[(e)-octadec-9-enoyl]oxypropyl] (e)-octadec-9-enoate Chemical compound CCCCCCCC\C=C\CCCCCCCC(=O)OCC(COP(O)(=O)OCCO)OC(=O)CCCCCCC\C=C\CCCCCCCC HMNZFMSWFCAGGW-XPWSMXQVSA-N 0.000 description 5
- 238000002617 apheresis Methods 0.000 description 5
- 239000004202 carbamide Substances 0.000 description 5
- 230000000295 complement effect Effects 0.000 description 5
- 239000002299 complementary DNA Substances 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 230000014509 gene expression Effects 0.000 description 5
- 238000011534 incubation Methods 0.000 description 5
- 108700042226 ras Genes Proteins 0.000 description 5
- 238000002798 spectrophotometry method Methods 0.000 description 5
- UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 description 4
- 229930024421 Adenine Natural products 0.000 description 4
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 4
- 108091026890 Coding region Proteins 0.000 description 4
- UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 description 4
- 108010054147 Hemoglobins Proteins 0.000 description 4
- 102000001554 Hemoglobins Human genes 0.000 description 4
- 238000012408 PCR amplification Methods 0.000 description 4
- 229910019142 PO4 Inorganic materials 0.000 description 4
- 229960000643 adenine Drugs 0.000 description 4
- UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 description 4
- 231100000673 dose–response relationship Toxicity 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- 239000002502 liposome Substances 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 4
- 239000010452 phosphate Substances 0.000 description 4
- 150000008300 phosphoramidites Chemical class 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- 208000028782 Hereditary disease Diseases 0.000 description 3
- 208000026350 Inborn Genetic disease Diseases 0.000 description 3
- 208000024556 Mendelian disease Diseases 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 244000301083 Ustilago maydis Species 0.000 description 3
- 235000015919 Ustilago maydis Nutrition 0.000 description 3
- 210000002798 bone marrow cell Anatomy 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000000432 density-gradient centrifugation Methods 0.000 description 3
- 208000016361 genetic disease Diseases 0.000 description 3
- 102000018146 globin Human genes 0.000 description 3
- 208000034737 hemoglobinopathy Diseases 0.000 description 3
- 208000018337 inherited hemoglobinopathy Diseases 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 230000002503 metabolic effect Effects 0.000 description 3
- 230000009871 nonspecific binding Effects 0.000 description 3
- 229920002401 polyacrylamide Polymers 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 230000008707 rearrangement Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 108091008146 restriction endonucleases Proteins 0.000 description 3
- 238000012552 review Methods 0.000 description 3
- 238000012163 sequencing technique Methods 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- 238000003146 transient transfection Methods 0.000 description 3
- 238000002054 transplantation Methods 0.000 description 3
- 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 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 2
- 238000007399 DNA isolation Methods 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 108700024394 Exon Proteins 0.000 description 2
- 208000020322 Gaucher disease type I Diseases 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 108091092195 Intron Proteins 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 241001529936 Murinae Species 0.000 description 2
- 239000012979 RPMI medium Substances 0.000 description 2
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 2
- 238000012300 Sequence Analysis Methods 0.000 description 2
- 108010006785 Taq Polymerase Proteins 0.000 description 2
- 239000007984 Tris EDTA buffer Substances 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000001464 adherent effect Effects 0.000 description 2
- 239000011543 agarose gel Substances 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 239000000908 ammonium hydroxide Substances 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 229960002092 busulfan Drugs 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 239000013592 cell lysate Substances 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 210000004748 cultured cell Anatomy 0.000 description 2
- 230000009089 cytolysis Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 238000001502 gel electrophoresis Methods 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 210000003494 hepatocyte Anatomy 0.000 description 2
- 230000006801 homologous recombination Effects 0.000 description 2
- 238000002744 homologous recombination Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000000329 molecular dynamics simulation Methods 0.000 description 2
- 210000001616 monocyte Anatomy 0.000 description 2
- 210000005087 mononuclear cell Anatomy 0.000 description 2
- DSWNRHCOGVRDOE-UHFFFAOYSA-N n,n-dimethylmethanimidamide Chemical compound CN(C)C=N DSWNRHCOGVRDOE-UHFFFAOYSA-N 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 230000002018 overexpression Effects 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 238000007894 restriction fragment length polymorphism technique Methods 0.000 description 2
- 239000012192 staining solution Substances 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000005945 translocation Effects 0.000 description 2
- HVCOBJNICQPDBP-UHFFFAOYSA-N 3-[3-[3,5-dihydroxy-6-methyl-4-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid;hydrate Chemical compound O.OC1C(OC(CC(=O)OC(CCCCCCC)CC(O)=O)CCCCCCC)OC(C)C(O)C1OC1C(O)C(O)C(O)C(C)O1 HVCOBJNICQPDBP-UHFFFAOYSA-N 0.000 description 1
- 206010052747 Adenocarcinoma pancreas Diseases 0.000 description 1
- 241000972773 Aulopiformes Species 0.000 description 1
- 101100214867 Autographa californica nuclear polyhedrosis virus AC53 gene Proteins 0.000 description 1
- 238000012935 Averaging Methods 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 1
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 1
- 101100327819 Caenorhabditis elegans chl-1 gene Proteins 0.000 description 1
- 101100368700 Caenorhabditis elegans tac-1 gene Proteins 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 229930105110 Cyclosporin A Natural products 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- 102100033934 DNA repair protein RAD51 homolog 2 Human genes 0.000 description 1
- 206010014561 Emphysema Diseases 0.000 description 1
- 229920001917 Ficoll Polymers 0.000 description 1
- 101710113436 GTPase KRas Proteins 0.000 description 1
- 208000020916 Gaucher disease type II Diseases 0.000 description 1
- 208000028735 Gaucher disease type III Diseases 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 229930186217 Glycolipid Natural products 0.000 description 1
- 208000009329 Graft vs Host Disease Diseases 0.000 description 1
- 208000031220 Hemophilia Diseases 0.000 description 1
- 208000009292 Hemophilia A Diseases 0.000 description 1
- 101100381516 Homo sapiens BCL2 gene Proteins 0.000 description 1
- 101001132307 Homo sapiens DNA repair protein RAD51 homolog 2 Proteins 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
- 102000000853 LDL receptors Human genes 0.000 description 1
- 108010001831 LDL receptors Proteins 0.000 description 1
- VTJUNIYRYIAIHF-IUCAKERBSA-N Leu-Pro Chemical group CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(O)=O VTJUNIYRYIAIHF-IUCAKERBSA-N 0.000 description 1
- OKIZCWYLBDKLSU-UHFFFAOYSA-M N,N,N-Trimethylmethanaminium chloride Chemical compound [Cl-].C[N+](C)(C)C OKIZCWYLBDKLSU-UHFFFAOYSA-M 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 108020005187 Oligonucleotide Probes Proteins 0.000 description 1
- 108020002230 Pancreatic Ribonuclease Proteins 0.000 description 1
- 102000005891 Pancreatic ribonuclease Human genes 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 108020005067 RNA Splice Sites Proteins 0.000 description 1
- 102000001218 Rec A Recombinases Human genes 0.000 description 1
- 108010055016 Rec A Recombinases Proteins 0.000 description 1
- 108091006629 SLC13A2 Proteins 0.000 description 1
- 108010016797 Sickle Hemoglobin Proteins 0.000 description 1
- 206010040642 Sickle cell anaemia with crisis Diseases 0.000 description 1
- 238000002105 Southern blotting Methods 0.000 description 1
- 206010043391 Thalassaemia beta Diseases 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 1
- 238000002679 ablation Methods 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000012382 advanced drug delivery Methods 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 150000005215 alkyl ethers Chemical group 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 238000011316 allogeneic transplantation Methods 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 238000000376 autoradiography Methods 0.000 description 1
- 230000037429 base substitution Effects 0.000 description 1
- 239000003114 blood coagulation factor Substances 0.000 description 1
- 239000000872 buffer 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
- 238000004113 cell culture Methods 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- YTRQFSDWAXHJCC-UHFFFAOYSA-N chloroform;phenol Chemical compound ClC(Cl)Cl.OC1=CC=CC=C1 YTRQFSDWAXHJCC-UHFFFAOYSA-N 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- 239000012568 clinical material Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000005138 cryopreservation Methods 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 229940084983 cyclophosphamide 50 mg Drugs 0.000 description 1
- 229930182912 cyclosporin Natural products 0.000 description 1
- 230000002435 cytoreductive effect Effects 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 230000000925 erythroid effect Effects 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 238000002146 exchange transfusion Methods 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 201000001386 familial hypercholesterolemia Diseases 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 231100000221 frame shift mutation induction Toxicity 0.000 description 1
- 230000037433 frameshift Effects 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000009429 hemophilia B Diseases 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 229940124589 immunosuppressive drug Drugs 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 108010057821 leucylproline Proteins 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 235000015250 liver sausages Nutrition 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 230000002132 lysosomal effect Effects 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 241001515942 marmosets Species 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 210000004967 non-hematopoietic stem cell Anatomy 0.000 description 1
- 239000002751 oligonucleotide probe Substances 0.000 description 1
- 201000002094 pancreatic adenocarcinoma Diseases 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 238000002205 phenol-chloroform extraction Methods 0.000 description 1
- 150000004713 phosphodiesters Chemical class 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 108010014186 ras Proteins Proteins 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000001054 red pigment Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 235000019515 salmon Nutrition 0.000 description 1
- 238000003345 scintillation counting Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000004017 serum-free culture medium Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000001131 transforming 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
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 230000009452 underexpressoin Effects 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 108700026220 vif Genes Proteins 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/795—Porphyrin- or corrin-ring-containing peptides
- C07K14/805—Haemoglobins; Myoglobins
-
- 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
- C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
-
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/13—Decoys
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/32—Chemical structure of the sugar
- C12N2310/321—2'-O-R Modification
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/50—Physical structure
- C12N2310/53—Physical structure partially self-complementary or closed
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Biophysics (AREA)
- Medicinal Chemistry (AREA)
- Microbiology (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Hematology (AREA)
- Pharmacology & Pharmacy (AREA)
- Diabetes (AREA)
- Gastroenterology & Hepatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Crystallography & Structural Chemistry (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/640517 | 1996-05-01 | ||
| US08/640,517 US5760012A (en) | 1996-05-01 | 1996-05-01 | Methods and compounds for curing diseases caused by mutations |
| PCT/US1997/007362 WO1997041141A1 (en) | 1996-05-01 | 1997-05-01 | Methods and compounds for curing diseases caused by mutations |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2822597A AU2822597A (en) | 1997-11-19 |
| AU708658B2 true AU708658B2 (en) | 1999-08-12 |
Family
ID=24568577
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU28225/97A Ceased AU708658B2 (en) | 1996-05-01 | 1997-05-01 | Methods and compounds for curing diseases caused by mutations |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US5760012A (enExample) |
| EP (1) | EP0906328A4 (enExample) |
| JP (1) | JP2000509282A (enExample) |
| KR (1) | KR20000064969A (enExample) |
| CN (1) | CN1207302C (enExample) |
| AU (1) | AU708658B2 (enExample) |
| CA (1) | CA2252762A1 (enExample) |
| NZ (1) | NZ332297A (enExample) |
| WO (1) | WO1997041141A1 (enExample) |
Families Citing this family (139)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5888983A (en) * | 1996-05-01 | 1999-03-30 | Thomas Jefferson University | Method and oligonucleobase compounds for curing diseases caused by mutations |
| US5731181A (en) * | 1996-06-17 | 1998-03-24 | Thomas Jefferson University | Chimeric mutational vectors having non-natural nucleotides |
| US20040266706A1 (en) * | 2002-11-05 | 2004-12-30 | Muthiah Manoharan | Cross-linked oligomeric compounds and their use in gene modulation |
| US6524613B1 (en) | 1997-04-30 | 2003-02-25 | Regents Of The University Of Minnesota | Hepatocellular chimeraplasty |
| KR20010022652A (ko) * | 1997-08-05 | 2001-03-26 | 키메라젠, 인크. | 식물에서 국소적인 유전자변형을 유발하기 위한 혼성 이중나선올리고뉴클레오티드의 용도 |
| US6004804A (en) | 1998-05-12 | 1999-12-21 | Kimeragen, Inc. | Non-chimeric mutational vectors |
| US6010907A (en) * | 1998-05-12 | 2000-01-04 | Kimeragen, Inc. | Eukaryotic use of non-chimeric mutational vectors |
| US6438561B1 (en) * | 1998-11-19 | 2002-08-20 | Navigation Technologies Corp. | Method and system for using real-time traffic broadcasts with navigation systems |
| US6368861B1 (en) | 1999-01-19 | 2002-04-09 | Maxygen, Inc. | Oligonucleotide mediated nucleic acid recombination |
| US20030054390A1 (en) * | 1999-01-19 | 2003-03-20 | Maxygen, Inc. | Oligonucleotide mediated nucleic acid recombination |
| US6917882B2 (en) * | 1999-01-19 | 2005-07-12 | Maxygen, Inc. | Methods for making character strings, polynucleotides and polypeptides having desired characteristics |
| US6376246B1 (en) | 1999-02-05 | 2002-04-23 | Maxygen, Inc. | Oligonucleotide mediated nucleic acid recombination |
| US6961664B2 (en) | 1999-01-19 | 2005-11-01 | Maxygen | Methods of populating data structures for use in evolutionary simulations |
| JP2002534965A (ja) | 1999-01-19 | 2002-10-22 | マキシジェン， インコーポレイテッド | 所望の特徴を有する文字ストリング、ポリヌクレオチドおよびポリペプチドを作製するための方法 |
| US7024312B1 (en) | 1999-01-19 | 2006-04-04 | Maxygen, Inc. | Methods for making character strings, polynucleotides and polypeptides having desired characteristics |
| US20070065838A1 (en) * | 1999-01-19 | 2007-03-22 | Maxygen, Inc. | Oligonucleotide mediated nucleic acid recombination |
| EP2368575B1 (en) * | 1999-04-08 | 2014-10-01 | Intercell USA, Inc. | Dry formulation for transcutaneous immunization |
| JP2003502288A (ja) * | 1999-05-21 | 2003-01-21 | ザユニバーシティー オブ マイアミ | 固体組織中の内因性ヌクレオチド配列を変化させるためのキメラ突然変異ベクターの使用 |
| EP1196559B1 (en) * | 1999-07-02 | 2006-07-05 | Invitrogen Corporation | Compositions and methods for enhanced sensitivity and specificity of nucleic acid synthesis |
| US6830902B1 (en) | 1999-07-02 | 2004-12-14 | Invitrogen Corporation | Compositions and methods for enhanced sensitivity and specificity of nucleic acid synthesis |
| US6271360B1 (en) * | 1999-08-27 | 2001-08-07 | Valigen (Us), Inc. | Single-stranded oligodeoxynucleotide mutational vectors |
| AR025996A1 (es) | 1999-10-07 | 2002-12-26 | Valigen Us Inc | Plantas no transgenicas resistentes a los herbicidas. |
| US7430477B2 (en) | 1999-10-12 | 2008-09-30 | Maxygen, Inc. | Methods of populating data structures for use in evolutionary simulations |
| US6656700B2 (en) | 2000-05-26 | 2003-12-02 | Amersham Plc | Isoforms of human pregnancy-associated protein-E |
| US6686188B2 (en) | 2000-05-26 | 2004-02-03 | Amersham Plc | Polynucleotide encoding a human myosin-like polypeptide expressed predominantly in heart and muscle |
| WO2001094610A2 (en) * | 2000-06-05 | 2001-12-13 | Thomas Jefferson University | Binary hybrid mutational vectors |
| US6875907B2 (en) | 2000-09-13 | 2005-04-05 | Pioneer Hi-Bred International, Inc. | Antimicrobial peptides and methods of use |
| US20020123474A1 (en) * | 2000-10-04 | 2002-09-05 | Shannon Mark E. | Human GTP-Rho binding protein2 |
| EP1414840A4 (en) * | 2001-03-27 | 2005-04-13 | Univ Delaware | GENOMICS APPLICATIONS FOR MODIFIED OLIGONUCLEOTIDES |
| US20030045830A1 (en) * | 2001-04-17 | 2003-03-06 | De Bizemont Therese | Gene therapy with chimeric oligonucleotides delivered by a method comprising a step of iontophoresis |
| US20040063922A1 (en) * | 2001-04-17 | 2004-04-01 | Conrad Charles A. | Methods and compositions for catalytic DNA exchange in a sequence specific manner |
| US20040078837A1 (en) * | 2001-08-02 | 2004-04-22 | Shannon Mark E. | Four human zinc-finger-containing proteins: MDZ3, MDZ4, MDZ7 and MDZ12 |
| WO2003013226A2 (en) * | 2001-08-09 | 2003-02-20 | Cibus Genetics | Non-transgenic herbicide resistant plants |
| US20030207327A1 (en) * | 2001-09-27 | 2003-11-06 | Kmiec Eric B. | Coisogenic eukaryotic cell collections |
| US7468244B2 (en) * | 2001-09-27 | 2008-12-23 | University Of Delaware | Polymorphism detection and separation |
| US7566535B2 (en) * | 2002-03-07 | 2009-07-28 | University Of Delaware | Enhanced oligonucleotide-mediated nucleic acid sequence alteration |
| EP1527176B2 (en) | 2002-08-05 | 2017-03-22 | Silence Therapeutics GmbH | Further novel forms of interfering rna molecules |
| AU2003282477A1 (en) * | 2002-10-07 | 2004-05-04 | Napro Bio Therapeutics, Inc. | Methods and compositions for reducing screening in oligonucleotide-directed nucleic acid sequence alteration |
| AU2003283217A1 (en) * | 2002-12-03 | 2004-06-23 | Aarhus Amt | Method for determing predisposition to manifestation of immune system related diseases |
| US20050025753A1 (en) * | 2003-04-30 | 2005-02-03 | Wei Han | Methods for production of non-disease causing hemoglobin by ex vivo oligonucleotide gene editing of human stem/progenitor cells |
| US20070072815A1 (en) * | 2004-05-04 | 2007-03-29 | Kmiec Eric B | Methods and kits to increase the efficiency of oligonucleotide-directed nucleic acid sequence alteration |
| WO2006071219A1 (en) | 2004-12-28 | 2006-07-06 | Pioneer Hi-Bred International, Inc. | Improved grain quality through altered expression of seed proteins |
| WO2006091194A1 (en) | 2005-02-23 | 2006-08-31 | North Carolina State University | Alteration of tobacco alkaloid content through modification of specific cytochrome p450 genes |
| WO2006119775A2 (en) | 2005-05-11 | 2006-11-16 | Aarhus Universitet | Method for diagnosis and treatment, of a mental disease |
| US20060272057A1 (en) | 2005-05-25 | 2006-11-30 | Pioneer Hi-Bred International, Inc. | Methods for improving crop plant architecture and yield |
| CN1880458B (zh) * | 2005-06-15 | 2010-04-28 | 中国医学科学院基础医学研究所 | 人β-珠蛋白基因簇的人源染色体打靶载体及其应用 |
| CN101356279A (zh) | 2005-11-10 | 2009-01-28 | 先锋高级育种国际公司 | Dof(具有一指的dna结合)序列和使用方法 |
| US20070199096A1 (en) | 2005-11-14 | 2007-08-23 | E.I. Du Pont De Nemours And Company | Compositions and Methods for Altering Alpha- and Beta-Tocotrienol Content |
| US7592505B2 (en) | 2005-12-30 | 2009-09-22 | Pioneer Hi-Bred International, Inc. | UDP-xylose synthases (UXS) polynucleotides, polypeptides, and uses thereof |
| CA3077776C (en) | 2006-01-12 | 2022-10-04 | Cibus Europe B.V. | Epsps mutants |
| CA2821436A1 (en) | 2006-02-09 | 2007-08-16 | Pioneer Hi-Bred International, Inc. | Genes for enhancing nitrogen utilization efficiency in crop plants |
| CA2649734A1 (en) | 2006-04-19 | 2007-11-01 | Pioneer Hi-Bred International, Inc. | Isolated polynucleotide molecules corresponding to mutant and wild-type alleles of the maize d9 gene and methods of use |
| AU2007363151B2 (en) * | 2006-06-28 | 2014-12-11 | Cibus Europe B.V. | Alkylester fatty acid blends and uses therefor |
| UA107442C2 (uk) | 2006-06-28 | 2015-01-12 | Nucelis Inc | Суміш жирних кислот та її застосування |
| UA125846C2 (uk) | 2007-04-04 | 2022-06-22 | Басф Плант Саєнс Гмбх | Мутант ahas |
| CN101679493A (zh) | 2007-05-25 | 2010-03-24 | 克罗普迪塞恩股份有限公司 | 在植物中通过调节玉米alfin的产量增强 |
| EA202092479A3 (ru) * | 2007-10-05 | 2021-06-30 | СИБАС ЕУРОП Би.Ви. | Растение и семя масличного рапса brassica napus, содержащие мутированные гены синтазы ацетогидроксикислот |
| US8124851B2 (en) | 2007-11-12 | 2012-02-28 | North Carolina State University | Alteration of tobacco alkaloid content through modification of specific cytochrome P450 genes |
| CN103952415A (zh) | 2007-11-20 | 2014-07-30 | 先锋国际良种公司 | 用于改善植物应激耐性的玉米乙烯信号转导基因及其调节 |
| WO2009143490A1 (en) | 2008-05-23 | 2009-11-26 | Cibus International, L.P. | Production of squalene using yeast |
| CN103834675A (zh) | 2008-09-26 | 2014-06-04 | 巴斯夫农化产品有限公司 | 除草剂-抗性的ahas-突变体及使用方法 |
| CN102197137A (zh) | 2008-10-30 | 2011-09-21 | 先锋国际良种公司 | 对谷氨酰胺合成酶(gs)进行操作以改善高等植物中的氮利用效率和籽粒产量 |
| CA2743707A1 (en) | 2008-12-04 | 2010-06-10 | Pioneer Hi-Bred International, Inc. | Methods and compositions for enhanced yield by targeted expression of knotted1 |
| AU2010204723A1 (en) | 2009-01-14 | 2011-08-18 | The Salk Institute For Biological Studies | Methods for screening and compounds that protect against amyloid diseases |
| US8716553B2 (en) | 2009-03-02 | 2014-05-06 | Pioneer Hi Bred International Inc | NAC transcriptional activators involved in abiotic stress tolerance |
| MX2011010845A (es) | 2009-04-14 | 2011-11-02 | Pioneer Hi Bred Int | La modulacion de acc sintasa mejora el rendimiento de las plantas en condiciones de bajo contenido de nitrogeno. |
| EP2427481A1 (en) | 2009-05-04 | 2012-03-14 | Pioneer Hi-Bred International Inc. | Yield enhancement in plants by modulation of ap2 transcription factor |
| CA2768571A1 (en) | 2009-07-24 | 2011-01-27 | Pioneer Hi-Bred International, Inc. | The use of dimerization domain component stacks to modulate plant architecture |
| WO2011017492A2 (en) | 2009-08-05 | 2011-02-10 | Pioneer Hi-Bred International, Inc. | Novel eto1 genes and use of same for reduced ethylene and improved stress tolerance in plants |
| EP2483404A1 (en) | 2009-10-02 | 2012-08-08 | Pioneer Hi-Bred International Inc. | Down-regulation of acc synthase for improved plant performance |
| DK2504421T3 (en) * | 2009-11-23 | 2017-05-22 | Nucelis Inc | METHODS AND COMPOSITIONS FOR PREPARING SQUAL USING Yeast |
| US20110191903A1 (en) | 2009-12-31 | 2011-08-04 | Pioneer Hi-Bred International, Inc. | Engineering plant resistance to diseases caused by pathogens |
| CN102906267A (zh) | 2010-01-06 | 2013-01-30 | 先锋国际良种公司 | 玉米光合作用组织和非光合作用组织昼夜节律的鉴定及其在改良作物方面的用途 |
| BR112012018616A2 (pt) | 2010-01-26 | 2017-01-10 | Pioneer Hi Bred Int | marcador de polinucleotídeo, polinucleotídeo isolado, polipeptídeo transportador abc isolado, planta, célula, semente, método para seleção de uma planta ou germoplasma de soja, método de introgressão de um alelo de resistência a herbicida em uma planta de soja, método para conferir tolerância ou tolerância melhorada a um ou mais herbicidas, método para controlar de modo seletivo plantas daninhas em um campo contendo uma cultura |
| WO2011139431A1 (en) | 2010-05-06 | 2011-11-10 | Pioneer Hi-Bred International, Inc. | Maize acc synthase 3 gene and protein and uses thereof |
| UA112969C2 (uk) | 2010-08-03 | 2016-11-25 | Сібас Юс Ллс | Рослина, стійка до одного або більше ррх-інгібуючих гербіцидів, яка містить мутантний ген протопорфіриноген ix оксидази (ррх) |
| US20120122223A1 (en) | 2010-08-03 | 2012-05-17 | Cibus Us Llc | Mutated protoporphyrinogen ix oxidase (ppx) genes |
| CN103237894A (zh) | 2010-08-13 | 2013-08-07 | 先锋国际良种公司 | 包含具有羟基苯丙酮酸双加氧酶(hppd)活性的序列的组合物和方法 |
| WO2012028673A1 (en) | 2010-09-02 | 2012-03-08 | Ludwig-Maximilians-Universitaet Muenchen | Spontaneous organogenesis in plants |
| EP2426204A1 (en) | 2010-09-02 | 2012-03-07 | Ludwig-Maximilians-Universität München | Spontaneous nodule organogenesis in plants |
| BR112013027860A2 (pt) | 2011-04-29 | 2016-11-29 | Pioneer Hi Bred Int | ácido nucleico isolado, planta ou célula vegetal, método para aumentar a capacidade do dreno, acelerar a remobilização e/ou a senescência e a secagem de grão em uma planta, método para aumentar a tolerância a seca na ausência de uma penalidade de produtividade sob condições sem seca, cassete de expressão e método para reduzir a expressão de zmme293 ou a atividade de zmme293 em uma planta |
| WO2012174139A2 (en) | 2011-06-14 | 2012-12-20 | Synthon Biopharmaceuticals B.V. | Compositions and methods for making and b ioc ont aining auxotrophic transgenic plants |
| US20130097734A1 (en) | 2011-07-12 | 2013-04-18 | Two Blades Foundation | Late blight resistance genes |
| CN104093842B (zh) | 2011-10-31 | 2016-12-07 | 先锋国际良种公司 | 改善植物耐旱性、氮利用效率和产量 |
| WO2013138309A1 (en) | 2012-03-13 | 2013-09-19 | Pioneer Hi-Bred International, Inc. | Genetic reduction of male fertility in plants |
| CN104703998B (zh) | 2012-03-13 | 2020-08-21 | 先锋国际良种公司 | 植物中雄性育性的遗传减少 |
| US10045499B2 (en) | 2012-05-24 | 2018-08-14 | Iowa State University Research Foundation, Inc. | Arabidopsis nonhost resistance gene(s) and use thereof to engineer disease resistant plants |
| WO2014011901A2 (en) * | 2012-07-11 | 2014-01-16 | Sangamo Biosciences, Inc. | Methods and compositions for delivery of biologics |
| EP2885411B1 (en) | 2012-08-16 | 2018-12-05 | VIB vzw | Means and methods for altering the lignin pathway in plants |
| CN105008541A (zh) | 2012-12-21 | 2015-10-28 | 先锋国际良种公司 | 用于生长素类似物缀合的组合物和方法 |
| WO2014164014A1 (en) | 2013-03-11 | 2014-10-09 | Pioneer Hi-Bred International, Inc. | Genes for improving nutrient uptake and abiotic stress tolerance in plants |
| US9803214B2 (en) | 2013-03-12 | 2017-10-31 | Pioneer Hi-Bred International, Inc. | Breeding pair of wheat plants comprising an MS45 promoter inverted repeat that confers male sterility and a construct that restores fertility |
| WO2014164074A1 (en) | 2013-03-13 | 2014-10-09 | Pioneer Hi-Bred International, Inc. | Enhanced nitrate uptake and nitrate translocation by over-expressing maize functional low-affinity nitrate transporters in transgenic maize |
| US20160017360A1 (en) | 2013-03-13 | 2016-01-21 | Pioneer Hi-Bred International, Inc. | Functional expression of bacterial major facilitator superfamily mfs gene in maize to improve agronomic traits and grain yield |
| CN105358696A (zh) | 2013-03-14 | 2016-02-24 | 希博斯美国有限公司 | 突变的丙二烯氧合酶2(aos2)基因 |
| CN105143248A (zh) | 2013-03-14 | 2015-12-09 | 先锋国际良种公司 | 玉蜀黍胁迫相关转录因子18及其用途 |
| WO2014152507A2 (en) | 2013-03-15 | 2014-09-25 | Pioneer Hi-Bred International, Inc. | Modulation of acc deaminase expression |
| CA2903555A1 (en) | 2013-03-15 | 2014-09-18 | Pioneer Hi-Bred International, Inc. | Compositions and methods of use of acc oxidase polynucleotides and polypeptides |
| HUE058351T2 (hu) | 2013-03-15 | 2022-07-28 | Cibus Us Llc | Célzott génmódosítás oligonukleotid-közvetített génjavítás alkalmazásával |
| US12331303B2 (en) | 2013-03-15 | 2025-06-17 | Cibus Us Llc | Methods and compositions for increasing efficiency of targeted gene modification using oligonucleotide-mediated gene repair |
| ES2921207T3 (es) | 2013-03-15 | 2022-08-19 | Cibus Us Llc | Procedimientos y composiciones para aumentar la eficiencia de la modificación genética direccionada utilizando la reparación genética mediada por oligonucleótidos |
| US9957515B2 (en) | 2013-03-15 | 2018-05-01 | Cibus Us Llc | Methods and compositions for targeted gene modification |
| US10017778B2 (en) | 2013-03-21 | 2018-07-10 | Vib Vzw | Means and methods for the reduction of photorespiration in crops |
| US11459579B2 (en) | 2013-07-09 | 2022-10-04 | Board Of Trustees Of Michigan State University | Transgenic plants produced with a K-domain, and methods and expression cassettes related thereto |
| WO2015006105A1 (en) | 2013-07-09 | 2015-01-15 | Board Of Trustees Of Michigan State University | Transgenic plants produced with a k-domain, and methods and expression cassettes related thereto |
| US20170166920A1 (en) | 2014-01-30 | 2017-06-15 | Two Blades Foundation | Plants with enhanced resistance to phytophthora |
| US20170081674A1 (en) | 2014-03-14 | 2017-03-23 | Cibus Us Llc | Methods and compositions for increasing efficiency of targeted gene modification using oligonucleotide-mediated gene repair |
| WO2015171603A1 (en) | 2014-05-06 | 2015-11-12 | Two Blades Foundation | Methods for producing plants with enhanced resistance to oomycete pathogens |
| CA2954201A1 (en) | 2014-07-08 | 2016-01-14 | Vib Vzw | Means and methods to increase plant yield |
| US10435700B2 (en) | 2014-10-06 | 2019-10-08 | Altria Client Services Llc | Genetic control of axillary bud growth in tobacco plants |
| WO2016100309A1 (en) | 2014-12-16 | 2016-06-23 | Pioneer Hi-Bred International, Inc. | Restoration of male fertility in wheat |
| CN107709564B (zh) | 2015-05-09 | 2021-11-02 | 双刃基金会 | 来自少花龙葵的抗晚疫病基因及使用方法 |
| WO2017062790A1 (en) | 2015-10-09 | 2017-04-13 | Two Blades Foundation | Cold shock protein receptors and methods of use |
| EA201891629A1 (ru) | 2016-02-09 | 2019-03-29 | Сибас Юс Ллс | Способы и композиции для повышения эффективности нацеленной модификации генов с применением опосредуемой олигонуклеотидами репарации генов |
| CN117126815A (zh) | 2016-03-11 | 2023-11-28 | 奥驰亚客户服务有限公司 | 用于生产烟杈减少或消除的烟草植物和制品的组合物和方法 |
| JP7066126B2 (ja) | 2016-08-09 | 2022-05-13 | ブイアイビー ブイゼットダブリュ | セルロースシンターゼ阻害剤および突然変異体植物 |
| EP3523439A1 (en) | 2016-10-07 | 2019-08-14 | Altria Client Services LLC | Composition and methods for producing tobacco plants and products having reduced tobacco-specific nitrosamines (tsnas) |
| CA3047121A1 (en) | 2016-12-16 | 2018-06-21 | Two Blades Foundation | Late blight resistance genes and methods of use |
| WO2018140214A1 (en) | 2017-01-24 | 2018-08-02 | Pioneer Hi-Bred International, Inc. | Nematicidal protein from pseudomonas |
| WO2019023587A1 (en) | 2017-07-28 | 2019-01-31 | Two Blades Foundation | POTYVIRUS RESISTANCE GENES AND METHODS OF USE |
| EP3682011A1 (en) | 2017-09-11 | 2020-07-22 | Altria Client Services LLC | Compositions and methods for producing tobacco plants and products having reduced or eliminated suckers |
| WO2019108619A1 (en) | 2017-11-28 | 2019-06-06 | Two Blades Foundation | Methods and compositions for enhancing the disease resistance of plants |
| US11034969B2 (en) | 2017-12-22 | 2021-06-15 | Altria Client Services Llc | Plant comprising recombinant polynucleotides encoding a pigment regulatory transcription factor with a tissue-preferred promoter |
| CA3087266A1 (en) | 2018-01-09 | 2019-07-18 | Cibus Us Llc | Shatterproof genes and mutations |
| CN111954464A (zh) | 2018-01-12 | 2020-11-17 | 双刃基金会 | 秆锈病抗性基因及使用方法 |
| US11377665B2 (en) | 2018-04-03 | 2022-07-05 | Altria Client Services Llc | Composition and methods for producing tobacco plants and products having increased phenylalanine and reduced tobacco-specific nitrosamines (TSNAs) |
| EP3772905A4 (en) | 2018-04-04 | 2022-01-05 | Cibus US LLC | FAD2 GENES AND MUTATIONS |
| GB201815670D0 (en) * | 2018-09-26 | 2018-11-07 | Univ Oxford Innovation Ltd | Protein editing |
| CN113660857A (zh) | 2019-01-24 | 2021-11-16 | 奥驰亚客户服务有限公司 | 包含降低的烟碱和降低的烟草特异性亚硝胺的烟草植物 |
| CN112111528B (zh) * | 2019-06-21 | 2024-04-02 | 华东师范大学 | 一种内含子异常剪接的修复方法 |
| US20220251595A1 (en) | 2019-06-27 | 2022-08-11 | Two Blades Foundation | Engineered atrlp23 pattern recognition receptors and methods of use |
| US20210071193A1 (en) | 2019-07-12 | 2021-03-11 | The Regents Of The University Of California | Plants with enhanced resistance to bacterial pathogens |
| WO2022240931A1 (en) | 2021-05-11 | 2022-11-17 | Two Blades Foundation | Methods for preparing a library of plant disease resistance genes for functional testing for disease resistance |
| WO2023012342A1 (en) | 2021-08-06 | 2023-02-09 | Kws Vegetables B.V. | Durable downy mildew resistance in spinach |
| WO2023056269A1 (en) | 2021-09-30 | 2023-04-06 | Two Blades Foundation | Plant disease resistance genes against stem rust and methods of use |
| EP4460571A1 (en) | 2022-01-05 | 2024-11-13 | Vib Vzw | Means and methods to increase abiotic stress tolerance in plants |
| WO2023131637A1 (en) | 2022-01-06 | 2023-07-13 | Vib Vzw | Improved silage grasses |
| WO2023144199A1 (en) | 2022-01-26 | 2023-08-03 | Vib Vzw | Plants having reduced levels of bitter taste metabolites |
| WO2025019221A1 (en) | 2023-07-15 | 2025-01-23 | Two Blades Foundation | Broad-spectrum polerovirus resistance gene |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE733059T1 (de) * | 1993-12-09 | 1997-08-28 | Univ Jefferson | Verbindungen und verfahren zur ortsspezifischen mutation in eukaryotischen zellen |
-
1996
- 1996-05-01 US US08/640,517 patent/US5760012A/en not_active Expired - Fee Related
-
1997
- 1997-05-01 CN CNB971959498A patent/CN1207302C/zh not_active Expired - Fee Related
- 1997-05-01 CA CA002252762A patent/CA2252762A1/en not_active Abandoned
- 1997-05-01 WO PCT/US1997/007362 patent/WO1997041141A1/en not_active Ceased
- 1997-05-01 EP EP97922597A patent/EP0906328A4/en not_active Withdrawn
- 1997-05-01 JP JP9539227A patent/JP2000509282A/ja not_active Ceased
- 1997-05-01 KR KR1019980708445A patent/KR20000064969A/ko not_active Ceased
- 1997-05-01 AU AU28225/97A patent/AU708658B2/en not_active Ceased
- 1997-05-01 NZ NZ332297A patent/NZ332297A/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| KR20000064969A (ko) | 2000-11-06 |
| EP0906328A1 (en) | 1999-04-07 |
| EP0906328A4 (en) | 2003-06-18 |
| NZ332297A (en) | 2000-03-27 |
| WO1997041141A1 (en) | 1997-11-06 |
| CA2252762A1 (en) | 1997-11-06 |
| JP2000509282A (ja) | 2000-07-25 |
| CN1223660A (zh) | 1999-07-21 |
| US5760012A (en) | 1998-06-02 |
| AU2822597A (en) | 1997-11-19 |
| CN1207302C (zh) | 2005-06-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU708658B2 (en) | Methods and compounds for curing diseases caused by mutations | |
| US5888983A (en) | Method and oligonucleobase compounds for curing diseases caused by mutations | |
| US5731181A (en) | Chimeric mutational vectors having non-natural nucleotides | |
| US7258854B2 (en) | Targeted chromosomal genomic alterations with modified single stranded oligonucleotides | |
| US7226785B2 (en) | Targeted chromosomal genomic alterations with modified single stranded oligonucleotides | |
| CA2118235C (en) | Synthetic antisense oligodeoxynucleotides and pharmaceutical compositions containing them | |
| CA3093702A1 (en) | Systems and methods for the treatment of hemoglobinopathies | |
| US20110262406A1 (en) | Compositions and methods for targeted inactivation of hiv cell surface receptors | |
| CN109414449A (zh) | 利用和不利用可设计核酸酶编辑基因组的改进方法 | |
| CA2205075C (en) | Reagent and method for inhibition of n-ras expression | |
| JP2010515464A (ja) | Ｈｉｖ細胞表面受容体の標的化不活性化のための組成物および方法 | |
| WO1992022303A1 (en) | Selective inhibition of leukemic cell proliferation by bcr-abl antisense oligonucleotides | |
| EP0722342A1 (en) | REGULATION OF bcl-2 GENE EXPRESSION | |
| WO1996040271A1 (en) | Treatment of hemoglobinopathies | |
| Clark | Antisense therapeutics in chronic myeloid leukaemia: the promise, the progress and the problems | |
| EP4558634A1 (en) | Tandem guide rnas (tg-rnas) and their use in genome editing | |
| TW202111122A (zh) | 藉靶向dmpk基因治療肌肉萎縮症之方法 | |
| AU2001249488C8 (en) | Targeted chromosomal genomic alterations with modified single stranded oligonucleotides | |
| ZA200207742B (en) | Targeted chromosomal genomic alterations with modified single stranded oligonucleotides. | |
| AU2001249488A1 (en) | Targeted chromosomal genomic alterations with modified single stranded oligonucleotides |