CA2259139A1 - Cationic polymer and lipoprotein-containing system for gene delivery - Google Patents
Cationic polymer and lipoprotein-containing system for gene delivery Download PDFInfo
- Publication number
- CA2259139A1 CA2259139A1 CA002259139A CA2259139A CA2259139A1 CA 2259139 A1 CA2259139 A1 CA 2259139A1 CA 002259139 A CA002259139 A CA 002259139A CA 2259139 A CA2259139 A CA 2259139A CA 2259139 A1 CA2259139 A1 CA 2259139A1
- Authority
- CA
- Canada
- Prior art keywords
- composition
- nucleic acid
- lipoprotein
- stearyl
- weight
- 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
- 102000004895 Lipoproteins Human genes 0.000 title claims abstract description 34
- 108090001030 Lipoproteins Proteins 0.000 title claims abstract description 34
- 238000001476 gene delivery Methods 0.000 title description 10
- 229920006317 cationic polymer Polymers 0.000 title description 3
- 239000000203 mixture Substances 0.000 claims abstract description 72
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 42
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 42
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 42
- 238000000034 method Methods 0.000 claims abstract description 33
- 239000013612 plasmid Substances 0.000 claims abstract description 29
- 108091034117 Oligonucleotide Proteins 0.000 claims abstract description 19
- 229920000249 biocompatible polymer Polymers 0.000 claims abstract description 19
- 230000002209 hydrophobic effect Effects 0.000 claims abstract description 18
- 108010007622 LDL Lipoproteins Proteins 0.000 claims description 50
- 102000007330 LDL Lipoproteins Human genes 0.000 claims description 50
- 108010038025 stearyl-poly(lysine) Proteins 0.000 claims description 39
- -1 poly(L-lysine) Polymers 0.000 claims description 31
- 229920000729 poly(L-lysine) polymer Polymers 0.000 claims description 29
- 229920000642 polymer Polymers 0.000 claims description 19
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 12
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 7
- 108010010234 HDL Lipoproteins Proteins 0.000 claims description 6
- 102000015779 HDL Lipoproteins Human genes 0.000 claims description 6
- 230000012010 growth Effects 0.000 claims description 6
- 108010062497 VLDL Lipoproteins Proteins 0.000 claims description 5
- 238000000338 in vitro Methods 0.000 claims description 4
- 229920006395 saturated elastomer Polymers 0.000 claims description 4
- 150000001768 cations Chemical class 0.000 claims description 3
- 230000002349 favourable effect Effects 0.000 claims description 3
- 238000012258 culturing Methods 0.000 claims description 2
- 230000001131 transforming effect Effects 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 abstract description 4
- 230000009881 electrostatic interaction Effects 0.000 abstract description 4
- 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 abstract description 2
- 210000004027 cell Anatomy 0.000 description 58
- 108020004414 DNA Proteins 0.000 description 38
- 238000001890 transfection Methods 0.000 description 16
- 231100000135 cytotoxicity Toxicity 0.000 description 8
- 230000003013 cytotoxicity Effects 0.000 description 8
- 108090000623 proteins and genes Proteins 0.000 description 8
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 6
- 239000012091 fetal bovine serum Substances 0.000 description 6
- 108010087776 Proto-Oncogene Proteins c-myb Proteins 0.000 description 5
- 102000009096 Proto-Oncogene Proteins c-myb Human genes 0.000 description 5
- 239000000074 antisense oligonucleotide Substances 0.000 description 5
- 238000012230 antisense oligonucleotides Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000001415 gene therapy Methods 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 5
- WHTVZRBIWZFKQO-AWEZNQCLSA-N (S)-chloroquine Chemical compound ClC1=CC=C2C(N[C@@H](C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-AWEZNQCLSA-N 0.000 description 4
- 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 4
- 238000004458 analytical method Methods 0.000 description 4
- 229960003677 chloroquine Drugs 0.000 description 4
- WHTVZRBIWZFKQO-UHFFFAOYSA-N chloroquine Natural products ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-UHFFFAOYSA-N 0.000 description 4
- 238000001556 precipitation Methods 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- 230000002776 aggregation Effects 0.000 description 3
- 238000004220 aggregation Methods 0.000 description 3
- 125000002091 cationic group Chemical group 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000002502 liposome Substances 0.000 description 3
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 108010001831 LDL receptors Proteins 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 230000001028 anti-proliverative effect Effects 0.000 description 2
- 238000002983 circular dichroism Methods 0.000 description 2
- 238000001142 circular dichroism spectrum Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000012202 endocytosis Effects 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 101150066555 lacZ gene Proteins 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 102000017172 low-density lipoprotein particle receptor activity proteins Human genes 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- 230000002080 lysosomotropic effect Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000013598 vector Substances 0.000 description 2
- 101150084750 1 gene Proteins 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- WSULSMOGMLRGKU-UHFFFAOYSA-N 1-bromooctadecane Chemical compound CCCCCCCCCCCCCCCCCCBr WSULSMOGMLRGKU-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- KUWPCJHYPSUOFW-YBXAARCKSA-N 2-nitrophenyl beta-D-galactoside Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1OC1=CC=CC=C1[N+]([O-])=O KUWPCJHYPSUOFW-YBXAARCKSA-N 0.000 description 1
- 101150033839 4 gene Proteins 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 101100037762 Caenorhabditis elegans rnh-2 gene Proteins 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 108091029865 Exogenous DNA Proteins 0.000 description 1
- 102000002464 Galactosidases Human genes 0.000 description 1
- 108010093031 Galactosidases Proteins 0.000 description 1
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
- 240000000233 Melia azedarach Species 0.000 description 1
- 229930191564 Monensin Natural products 0.000 description 1
- GAOZTHIDHYLHMS-UHFFFAOYSA-N Monensin A Natural products O1C(CC)(C2C(CC(O2)C2C(CC(C)C(O)(CO)O2)C)C)CCC1C(O1)(C)CCC21CC(O)C(C)C(C(C)C(OC)C(C)C(O)=O)O2 GAOZTHIDHYLHMS-UHFFFAOYSA-N 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 101100252165 Mus musculus Rnd2 gene Proteins 0.000 description 1
- 238000007126 N-alkylation reaction Methods 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 101710185500 Small t antigen Proteins 0.000 description 1
- 108700009124 Transcription Initiation Site Proteins 0.000 description 1
- 108700005077 Viral Genes Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 229920002988 biodegradable polymer Polymers 0.000 description 1
- 239000004621 biodegradable polymer Substances 0.000 description 1
- 239000012888 bovine serum Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000004700 cellular uptake Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000007398 colorimetric assay Methods 0.000 description 1
- 230000009918 complex formation Effects 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 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 1
- 229960005542 ethidium bromide Drugs 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical group 0.000 description 1
- 108010064060 high density lipoprotein receptors Proteins 0.000 description 1
- 102000054823 high-density lipoprotein particle receptor activity proteins Human genes 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000002356 laser light scattering Methods 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 229960005358 monensin Drugs 0.000 description 1
- GAOZTHIDHYLHMS-KEOBGNEYSA-N monensin A Chemical compound C([C@@](O1)(C)[C@H]2CC[C@@](O2)(CC)[C@H]2[C@H](C[C@@H](O2)[C@@H]2[C@H](C[C@@H](C)[C@](O)(CO)O2)C)C)C[C@@]21C[C@H](O)[C@@H](C)[C@@H]([C@@H](C)[C@@H](OC)[C@H](C)C(O)=O)O2 GAOZTHIDHYLHMS-KEOBGNEYSA-N 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 150000004713 phosphodiesters Chemical group 0.000 description 1
- 229920000740 poly(D-lysine) polymer Polymers 0.000 description 1
- 229920000724 poly(L-arginine) polymer Polymers 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 108010011110 polyarginine Proteins 0.000 description 1
- 210000002729 polyribosome Anatomy 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 230000010837 receptor-mediated endocytosis Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000005406 washing Methods 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
- C12N15/1135—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 against oncogenes or tumor suppressor genes
-
- 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
- C12N15/64—General methods for preparing the vector, for introducing it into the cell or for selecting the vector-containing host
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
- A61K47/645—Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6905—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion
- A61K47/6917—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion the form being a lipoprotein vesicle, e.g. HDL or LDL proteins
-
- 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
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
-
- 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
- C12N2310/30—Chemical structure
- C12N2310/35—Nature of the modification
- C12N2310/351—Conjugate
- C12N2310/3513—Protein; Peptide
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/29—Coated or structually defined flake, particle, cell, strand, strand portion, rod, filament, macroscopic fiber or mass thereof
- Y10T428/2982—Particulate matter [e.g., sphere, flake, etc.]
- Y10T428/2984—Microcapsule with fluid core [includes liposome]
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Organic Chemistry (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Veterinary Medicine (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Dispersion Chemistry (AREA)
- Oncology (AREA)
- Cell Biology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Compositions Of Macromolecular Compounds (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/675,120 | 1996-07-03 | ||
| US08/675,120 US5679559A (en) | 1996-07-03 | 1996-07-03 | Cationic polymer and lipoprotein-containing system for gene delivery |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2259139A1 true CA2259139A1 (en) | 1998-01-08 |
Family
ID=24709138
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002259139A Abandoned CA2259139A1 (en) | 1996-07-03 | 1997-07-03 | Cationic polymer and lipoprotein-containing system for gene delivery |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US5679559A (enExample) |
| EP (1) | EP0958369A4 (enExample) |
| JP (1) | JP2001501812A (enExample) |
| KR (1) | KR100536979B1 (enExample) |
| AU (1) | AU717109B2 (enExample) |
| CA (1) | CA2259139A1 (enExample) |
| NZ (1) | NZ333621A (enExample) |
| WO (1) | WO1998000556A1 (enExample) |
Families Citing this family (62)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE69725878T2 (de) | 1996-08-13 | 2004-07-29 | Chiron Corp. (N.D.Ges.D. Staates Delaware), Emeryville | Zusammensetzungen zur polynukleotidabgabe |
| US6635623B1 (en) | 1997-06-13 | 2003-10-21 | Baylor College Of Medicine | Lipoproteins as nucleic acid vectors |
| DE69838584T2 (de) | 1997-08-04 | 2008-06-26 | Cell Genesys, Inc., Foster City | Enhancer des menschlichen glandulären kallikreingens, vektoren die ihn enthalten und methoden für seine verwendung |
| US6197332B1 (en) * | 1997-08-13 | 2001-03-06 | Chiron Corporation | Lipid-conjugated polyamide compounds and related compositions and methods thereof |
| US5973119A (en) * | 1998-06-05 | 1999-10-26 | Amgen Inc. | Cyclin E genes and proteins |
| US6344541B1 (en) * | 1998-09-25 | 2002-02-05 | Amgen Inc. | DKR polypeptides |
| US7708993B2 (en) * | 1999-02-03 | 2010-05-04 | Amgen Inc. | Polypeptides involved in immune response |
| CN1309734C (zh) * | 1999-02-03 | 2007-04-11 | 安姆根有限公司 | 与免疫应答有关的新颖多肽 |
| US8624010B1 (en) | 1999-02-03 | 2014-01-07 | Steven K. Yoshinaga | Nucleic acids encoding B7RP1 |
| AU3770800A (en) | 1999-03-26 | 2000-10-16 | Amgen, Inc. | Beta secretase genes and polypeptides |
| US6281005B1 (en) | 1999-05-14 | 2001-08-28 | Copernicus Therapeutics, Inc. | Automated nucleic acid compaction device |
| WO2001013723A1 (en) * | 1999-08-20 | 2001-03-01 | Mirus Corporation | Charge reversal of polyion complexes |
| US7459540B1 (en) * | 1999-09-07 | 2008-12-02 | Amgen Inc. | Fibroblast growth factor-like polypeptides |
| US7408047B1 (en) | 1999-09-07 | 2008-08-05 | Amgen Inc. | Fibroblast growth factor-like polypeptides |
| US6900043B1 (en) | 1999-09-21 | 2005-05-31 | Amgen Inc. | Phosphatases which activate map kinase pathways |
| US20050239061A1 (en) * | 2000-03-01 | 2005-10-27 | Marshall William S | Identification and use of effectors and allosteric molecules for the alteration of gene expression |
| US7514239B2 (en) | 2000-03-28 | 2009-04-07 | Amgen Inc. | Nucleic acid molecules encoding beta-like glycoprotein hormone polypeptides and heterodimers thereof |
| CA2413547A1 (en) * | 2000-06-28 | 2002-01-03 | Amgen, Inc. | B7-like molecules and uses thereof |
| PT2077279E (pt) | 2000-06-28 | 2012-09-14 | Amgen Inc | Moléculas do receptor de linfopoietina estromal tímica e suas utilizações |
| MXPA03004578A (es) | 2000-11-28 | 2004-05-05 | Amgen Inc | Nuevos polipeptidos involucrados en respuesta inmune. |
| US6652886B2 (en) | 2001-02-16 | 2003-11-25 | Expression Genetics | Biodegradable cationic copolymers of poly (alkylenimine) and poly (ethylene glycol) for the delivery of bioactive agents |
| AU2003217693A1 (en) * | 2002-02-22 | 2003-09-09 | Board Of Trustees Of The University Of Illinois | Beta chain-associated regulator of apoptosis |
| US7662924B2 (en) * | 2002-02-22 | 2010-02-16 | The Board Of Trustees Of The University Of Illinois | Beta chain-associated regulator of apoptosis |
| US20030186916A1 (en) * | 2002-03-12 | 2003-10-02 | Lei Yu | Vector for transfection of eukaryotic cells |
| GB0212826D0 (en) * | 2002-05-31 | 2002-07-10 | Dna Res Innovations Ltd | Materials and methods relating to polyions and substance delivery |
| AU2003299971A1 (en) * | 2002-12-30 | 2004-07-29 | Amgen Inc. | Combination therapy with co-stimulatory factors |
| MXPA06012076A (es) * | 2004-04-20 | 2007-01-25 | Nastech Pharm Co | Metodos y composiciones para mejorar el suministro de arn bicatenario o un acido nucleico hibrido bicatenario para regular la expresion genetica en celulas de mamifero. |
| US20060040882A1 (en) * | 2004-05-04 | 2006-02-23 | Lishan Chen | Compostions and methods for enhancing delivery of nucleic acids into cells and for modifying expression of target genes in cells |
| US20060035815A1 (en) * | 2004-05-04 | 2006-02-16 | Nastech Pharmaceutical Company Inc. | Pharmaceutical compositions for delivery of ribonucleic acid to a cell |
| EP2298896A1 (en) | 2004-06-22 | 2011-03-23 | The Board of Trustees of the University of Illinois | Methods of inhibiting tumor cell proliferation with FOXM1 siRNA |
| GB0513702D0 (en) | 2005-07-04 | 2005-08-10 | Sterix Ltd | Compound |
| CA2621694A1 (en) * | 2005-09-08 | 2007-03-15 | Nastech Pharmaceutical Company Inc. | Pharmaceutical compositions for delivery of ribonucleic acid to a cell |
| US20100129460A1 (en) * | 2005-10-14 | 2010-05-27 | Nastech Pharmaceutical Company Inc. | Compounds and methods for peptide ribonucleic acid condensate particles for rna therapeutics |
| US20070281900A1 (en) * | 2006-05-05 | 2007-12-06 | Nastech Pharmaceutical Company Inc. | COMPOSITIONS AND METHODS FOR LIPID AND POLYPEPTIDE BASED siRNA INTRACELLULAR DELIVERY |
| US20070269892A1 (en) * | 2006-05-18 | 2007-11-22 | Nastech Pharmaceutical Company Inc. | FORMULATIONS FOR INTRACELLULAR DELIVERY dsRNA |
| US20070275923A1 (en) * | 2006-05-25 | 2007-11-29 | Nastech Pharmaceutical Company Inc. | CATIONIC PEPTIDES FOR siRNA INTRACELLULAR DELIVERY |
| US8282918B2 (en) * | 2007-07-30 | 2012-10-09 | University Of Iowa Research Foundation | Polynucleotides encoding RPA4/RPA32 hybrid polypeptides |
| CN101903018B (zh) * | 2007-10-17 | 2012-09-05 | 韩国科学技术院 | 用于递送核酸基因的ldl样阳离子纳米微粒、其制备方法以及使用其递送核酸基因的方法 |
| JOP20190083A1 (ar) | 2008-06-04 | 2017-06-16 | Amgen Inc | بولي ببتيدات اندماجية طافرة لـfgf21 واستخداماتها |
| EA032727B1 (ru) | 2008-10-10 | 2019-07-31 | Амген Инк. | Мутантный резистентный к протеолизу полипептид fgf21 и его применение |
| MX2011011815A (es) | 2009-05-05 | 2012-01-27 | Amgen Inc | Mutantes fgf21 y usos de los mismos. |
| PT3248610T (pt) | 2009-05-05 | 2024-02-01 | Amgen Inc | Mutantes fgf21 e suas utilizações |
| EP2443145A1 (en) * | 2009-06-17 | 2012-04-25 | Amgen, Inc | Chimeric fgf19 polypeptides and uses thereof |
| TWI373338B (en) * | 2009-08-27 | 2012-10-01 | Nat Univ Chung Cheng | Pharmaceutical composition containing transcription factor decoys and their preparation method and applications |
| BR112012010755A2 (pt) | 2009-11-05 | 2015-09-22 | Proyecto Biomedicina Cima Sl | constructo de gene que permite a expressão hepato-específica induzível de um polinucleotídeo de interesse em resposta a um agente indutor, vetor, genoma viral recombinante, vírion, método in vitro para a expressão de um polinucleotídeo de interesse em uma célula de origem hepática, composição farmacêutica e operador-promotor bi-direcional induzível adequado para a expressão hepato-específica induzível de dois polinucleotídeos de interesse por um agente indutor |
| EP2679234A3 (en) * | 2009-12-02 | 2014-04-23 | Amgen Inc. | Binding proteins that bind to human FGFR1C, human beta-klotho and both human FGFR1C and human beta-klotho |
| UA109888C2 (uk) | 2009-12-07 | 2015-10-26 | ІЗОЛЬОВАНЕ АНТИТІЛО АБО ЙОГО ФРАГМЕНТ, ЩО ЗВ'ЯЗУЄТЬСЯ З β-КЛОТО, РЕЦЕПТОРАМИ FGF І ЇХНІМИ КОМПЛЕКСАМИ | |
| EP3670534A3 (en) | 2010-04-15 | 2020-09-09 | Amgen Inc. | Human fgf receptor and beta-klotho binding proteins |
| EP3190187A1 (en) | 2010-05-21 | 2017-07-12 | Peptimed, Inc. | Reagents and methods for treating cancer |
| WO2012095548A2 (es) | 2011-01-13 | 2012-07-19 | Centro De Investigación Biomédica En Red De Enfermedades Neurodegenerativas (Ciberned) | Compuestos para el tratamiento de enfermedades neurodegenerativas |
| US9644038B2 (en) | 2011-12-21 | 2017-05-09 | The Regents Of The University Of California | Apolipoprotein nanodiscs with telodendrimer |
| US10005936B2 (en) * | 2012-11-23 | 2018-06-26 | Nanyang Technological University | Photoactive bioadhesive compositions |
| US9458246B2 (en) | 2013-03-13 | 2016-10-04 | Amgen Inc. | Proteins specific for BAFF and B7RP1 |
| PH12022550138A1 (en) | 2013-03-13 | 2023-03-06 | Amgen Inc | Proteins specific for baff and b7rp1 and uses thereof |
| US20160303242A1 (en) | 2013-12-09 | 2016-10-20 | Durect Corporation | Pharmaceutically Active Agent Complexes, Polymer Complexes, and Compositions and Methods Involving the Same |
| US12226529B2 (en) | 2015-08-25 | 2025-02-18 | Lawrence Livermore National Security, Llc | Stable nanolipoprotein particles and related compositions methods and systems |
| US10183058B2 (en) | 2016-06-17 | 2019-01-22 | Nymox Corporation | Method of preventing or reducing the progression of prostate cancer |
| US10172910B2 (en) | 2016-07-28 | 2019-01-08 | Nymox Corporation | Method of preventing or reducing the incidence of acute urinary retention |
| US10532081B2 (en) | 2016-09-07 | 2020-01-14 | Nymox Corporation | Method of ameliorating or preventing the worsening or the progression of symptoms of BPH |
| WO2018204421A2 (en) | 2017-05-02 | 2018-11-08 | Lawrence Livermore National Security, Llc | Momp telonanoparticles, and related compositions, methods and systems |
| WO2018204495A1 (en) * | 2017-05-02 | 2018-11-08 | Synthetic Genomics, Inc. | Nanolipoprotein particles and related compositions methods and systems for loading rna |
| HUE071069T2 (hu) | 2019-10-28 | 2025-07-28 | Medimmune Ltd | Tímusz sztrómális limfopoietint (TSLP) kötõ antitestek szárazpor készítményei és eljárások ezek alkalmazására |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5354844A (en) * | 1989-03-16 | 1994-10-11 | Boehringer Ingelheim International Gmbh | Protein-polycation conjugates |
| US4983401A (en) * | 1989-05-22 | 1991-01-08 | Kinaform Technology, Inc. | Sustained release pharmaceutical preparations having pH controlled membrane coatings |
-
1996
- 1996-07-03 US US08/675,120 patent/US5679559A/en not_active Expired - Lifetime
-
1997
- 1997-07-03 WO PCT/US1997/012425 patent/WO1998000556A1/en not_active Ceased
- 1997-07-03 EP EP97934981A patent/EP0958369A4/en not_active Withdrawn
- 1997-07-03 NZ NZ333621A patent/NZ333621A/en unknown
- 1997-07-03 AU AU38023/97A patent/AU717109B2/en not_active Ceased
- 1997-07-03 KR KR10-1999-7000048A patent/KR100536979B1/ko not_active Expired - Fee Related
- 1997-07-03 JP JP10504522A patent/JP2001501812A/ja not_active Ceased
- 1997-07-03 CA CA002259139A patent/CA2259139A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| KR20000023602A (ko) | 2000-04-25 |
| EP0958369A4 (en) | 2004-11-17 |
| US5679559A (en) | 1997-10-21 |
| JP2001501812A (ja) | 2001-02-13 |
| KR100536979B1 (ko) | 2005-12-14 |
| NZ333621A (en) | 1999-09-29 |
| AU717109B2 (en) | 2000-03-16 |
| AU3802397A (en) | 1998-01-21 |
| EP0958369A1 (en) | 1999-11-24 |
| WO1998000556A1 (en) | 1998-01-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU717109B2 (en) | Cationic polymer and lipoprotein-containing system for gene delivery | |
| Jeong et al. | Poly (L-lysine)-g-poly (D, L-lactic-co-glycolic acid) micelles for low cytotoxic biodegradable gene delivery carriers | |
| KR101761388B1 (ko) | 트랜스펙션 및 면역 자극을 위한 이황화-크로스링크된 양이온 성분 및 핵산의 복합체 | |
| Lee et al. | PEG grafted polylysine with fusogenic peptide for gene delivery: high transfection efficiency with low cytotoxicity | |
| Nimesh et al. | RETRACTED: Polyethylenimine nanoparticles as efficient transfecting agents for mammalian cells | |
| Debus et al. | Delivery of messenger RNA using poly (ethylene imine)–poly (ethylene glycol)-copolymer blends for polyplex formation: Biophysical characterization and in vitro transfection properties | |
| Dutta et al. | RETRACTED: Dendrimer nanocarriers as versatile vectors in gene delivery | |
| US7772201B2 (en) | Highly branched HK peptides as effective carriers of siRNA | |
| US8658150B2 (en) | Polymer derived from linear polyethylenimine for gene transfer | |
| Kabanov et al. | Efficient transformation of mammalian cells using DNA interpolyelectrolyte complexes with carbon chain polycations | |
| JP2007521247A (ja) | 生体適合性−遺伝子送達剤としての新規カチオン性リポポリマー | |
| CA2395636A1 (en) | Novel colloid synthetic vectors for gene therapy | |
| Cho et al. | Folate receptor-mediated intracellular delivery of recombinant caspase-3 for inducing apoptosis | |
| WO2004087931A1 (en) | Conjugate for gene transfer comprising oligonucleotide and hydrophilic polymer, polyelectrolyte complex micelles formed from the conjugate, and methods for preparation thereof | |
| Nimesh et al. | Guanidinium-grafted polyethylenimine: an efficient transfecting agent for mammalian cells | |
| EP1115428B1 (en) | Cationic dendrimeric compounds and their use as oligonucleotide/polynucleotide carriers | |
| US7163677B2 (en) | Cationic polymers having degradable crosslinks | |
| Kudsiova et al. | Delivery of siRNA using ternary complexes containing branched cationic peptides: the role of peptide sequence, branching and targeting | |
| KR19990063814A (ko) | 핵산 형질감염용으로 유용한 약학 조성물 및 이의 용도 | |
| AU1750400A (en) | Method for the immobilization of oligonucleotides | |
| AU2017242657A1 (en) | Synthetic compound for improving efficiency of transfection | |
| US20050153926A1 (en) | Method for the immobilization of oligonucleotides | |
| Arote et al. | Folate conjugated poly (ester amine) for lung cancer therapy | |
| Han et al. | Selective gene transfer to endometrial cancer cells by a polymer against matrix metalloproteinase 2 (MMP-2) | |
| AU2004212553A1 (en) | Method for the immobilization of oligonucleotides |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Dead |