CA2473434A1 - Methods for making polynucleotides and purifying double-stranded polynucleotides - Google Patents
Methods for making polynucleotides and purifying double-stranded polynucleotides Download PDFInfo
- Publication number
- CA2473434A1 CA2473434A1 CA002473434A CA2473434A CA2473434A1 CA 2473434 A1 CA2473434 A1 CA 2473434A1 CA 002473434 A CA002473434 A CA 002473434A CA 2473434 A CA2473434 A CA 2473434A CA 2473434 A1 CA2473434 A1 CA 2473434A1
- Authority
- CA
- Canada
- Prior art keywords
- library
- nucleic acid
- oligonucleotide
- polypeptide
- double
- 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
- 238000000034 method Methods 0.000 title claims abstract description 554
- 108091033319 polynucleotide Proteins 0.000 title claims abstract description 307
- 102000040430 polynucleotide Human genes 0.000 title claims abstract description 307
- 239000002157 polynucleotide Substances 0.000 title claims abstract description 307
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 483
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 478
- 229920001184 polypeptide Polymers 0.000 claims abstract description 476
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 380
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 364
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 364
- 230000027455 binding Effects 0.000 claims abstract description 192
- 239000000427 antigen Substances 0.000 claims abstract description 182
- 108091007433 antigens Proteins 0.000 claims abstract description 182
- 102000036639 antigens Human genes 0.000 claims abstract description 182
- 125000003729 nucleotide group Chemical group 0.000 claims abstract description 110
- 239000002773 nucleotide Substances 0.000 claims abstract description 109
- 238000012217 deletion Methods 0.000 claims abstract description 102
- 230000037430 deletion Effects 0.000 claims abstract description 102
- 238000003780 insertion Methods 0.000 claims abstract description 92
- 230000037431 insertion Effects 0.000 claims abstract description 92
- 108091028043 Nucleic acid sequence Proteins 0.000 claims abstract description 15
- 108700005078 Synthetic Genes Proteins 0.000 claims abstract description 10
- 108091034117 Oligonucleotide Proteins 0.000 claims description 398
- 108020004705 Codon Proteins 0.000 claims description 155
- 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 claims description 145
- 108091008146 restriction endonucleases Proteins 0.000 claims description 143
- 238000002703 mutagenesis Methods 0.000 claims description 139
- 231100000350 mutagenesis Toxicity 0.000 claims description 139
- 108090000623 proteins and genes Proteins 0.000 claims description 97
- 230000003321 amplification Effects 0.000 claims description 89
- 238000003199 nucleic acid amplification method Methods 0.000 claims description 89
- 238000006243 chemical reaction Methods 0.000 claims description 87
- 108091026890 Coding region Proteins 0.000 claims description 84
- 102000004190 Enzymes Human genes 0.000 claims description 56
- 108090000790 Enzymes Proteins 0.000 claims description 56
- 239000012634 fragment Substances 0.000 claims description 54
- 238000003752 polymerase chain reaction Methods 0.000 claims description 54
- 150000001413 amino acids Chemical class 0.000 claims description 53
- 108020004414 DNA Proteins 0.000 claims description 48
- 239000000758 substrate Substances 0.000 claims description 47
- 102000011724 DNA Repair Enzymes Human genes 0.000 claims description 39
- 210000004027 cell Anatomy 0.000 claims description 36
- 108010076525 DNA Repair Enzymes Proteins 0.000 claims description 32
- 239000011324 bead Substances 0.000 claims description 30
- 238000005304 joining Methods 0.000 claims description 30
- 239000003550 marker Substances 0.000 claims description 29
- 230000017730 intein-mediated protein splicing Effects 0.000 claims description 26
- 102000010645 MutS Proteins Human genes 0.000 claims description 25
- 108010038272 MutS Proteins Proteins 0.000 claims description 25
- 238000012216 screening Methods 0.000 claims description 25
- 238000013518 transcription Methods 0.000 claims description 24
- 230000035897 transcription Effects 0.000 claims description 24
- 238000005215 recombination Methods 0.000 claims description 22
- 230000006798 recombination Effects 0.000 claims description 22
- 210000001072 colon Anatomy 0.000 claims description 20
- 230000029087 digestion Effects 0.000 claims description 20
- 239000003155 DNA primer Substances 0.000 claims description 19
- 108010047041 Complementarity Determining Regions Proteins 0.000 claims description 18
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 17
- 239000002299 complementary DNA Substances 0.000 claims description 17
- 230000033607 mismatch repair Effects 0.000 claims description 17
- 238000002741 site-directed mutagenesis Methods 0.000 claims description 17
- 108020001507 fusion proteins Proteins 0.000 claims description 16
- 102000037865 fusion proteins Human genes 0.000 claims description 16
- 102000003960 Ligases Human genes 0.000 claims description 15
- 108090000364 Ligases Proteins 0.000 claims description 15
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 claims description 14
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 14
- 230000000295 complement effect Effects 0.000 claims description 14
- 108020001738 DNA Glycosylase Proteins 0.000 claims description 13
- 102000028381 DNA glycosylase Human genes 0.000 claims description 13
- 230000001580 bacterial effect Effects 0.000 claims description 13
- 238000000746 purification Methods 0.000 claims description 13
- 230000010076 replication Effects 0.000 claims description 13
- 239000007787 solid Substances 0.000 claims description 13
- 239000007858 starting material Substances 0.000 claims description 13
- 238000003786 synthesis reaction Methods 0.000 claims description 13
- 239000000539 dimer Substances 0.000 claims description 12
- 238000001727 in vivo Methods 0.000 claims description 11
- 230000001105 regulatory effect Effects 0.000 claims description 11
- 230000015572 biosynthetic process Effects 0.000 claims description 10
- 239000002777 nucleoside Substances 0.000 claims description 10
- 150000003833 nucleoside derivatives Chemical class 0.000 claims description 10
- 230000008685 targeting Effects 0.000 claims description 10
- 230000003115 biocidal effect Effects 0.000 claims description 9
- 238000012219 cassette mutagenesis Methods 0.000 claims description 9
- 238000002804 saturated mutagenesis Methods 0.000 claims description 9
- 102000012410 DNA Ligases Human genes 0.000 claims description 8
- 108010061982 DNA Ligases Proteins 0.000 claims description 8
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 claims description 8
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 claims description 8
- 102100026406 G/T mismatch-specific thymine DNA glycosylase Human genes 0.000 claims description 8
- 101710153534 G/U mismatch-specific DNA glycosylase Proteins 0.000 claims description 8
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 claims description 8
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 claims description 8
- 108010035344 Thymine DNA Glycosylase Proteins 0.000 claims description 8
- 239000000499 gel Substances 0.000 claims description 8
- 230000003100 immobilizing effect Effects 0.000 claims description 8
- 230000001965 increasing effect Effects 0.000 claims description 8
- 238000012163 sequencing technique Methods 0.000 claims description 8
- 108020000946 Bacterial DNA Proteins 0.000 claims description 7
- 238000007845 assembly PCR Methods 0.000 claims description 7
- 230000033590 base-excision repair Effects 0.000 claims description 7
- 229960002685 biotin Drugs 0.000 claims description 7
- 235000020958 biotin Nutrition 0.000 claims description 7
- 239000011616 biotin Substances 0.000 claims description 7
- 230000002950 deficient Effects 0.000 claims description 7
- 230000007717 exclusion Effects 0.000 claims description 7
- 230000001568 sexual effect Effects 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 7
- 238000011144 upstream manufacturing Methods 0.000 claims description 7
- 229940035893 uracil Drugs 0.000 claims description 7
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 claims description 6
- 241000588724 Escherichia coli Species 0.000 claims description 6
- 108010093801 endodeoxyribonuclease BstNBI Proteins 0.000 claims description 6
- 229930027917 kanamycin Natural products 0.000 claims description 6
- 229960000318 kanamycin Drugs 0.000 claims description 6
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 claims description 6
- 229930182823 kanamycin A Natural products 0.000 claims description 6
- 239000002245 particle Substances 0.000 claims description 6
- 230000008439 repair process Effects 0.000 claims description 6
- 230000003362 replicative effect Effects 0.000 claims description 6
- 108090001008 Avidin Proteins 0.000 claims description 5
- 210000000349 chromosome Anatomy 0.000 claims description 5
- 239000003623 enhancer Substances 0.000 claims description 5
- 239000013604 expression vector Substances 0.000 claims description 5
- 239000003446 ligand Substances 0.000 claims description 5
- 238000002823 phage display Methods 0.000 claims description 5
- 241001515965 unidentified phage Species 0.000 claims description 5
- 241001465754 Metazoa Species 0.000 claims description 4
- 229930182555 Penicillin Natural products 0.000 claims description 4
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 claims description 4
- 239000004793 Polystyrene Substances 0.000 claims description 4
- 239000003242 anti bacterial agent Substances 0.000 claims description 4
- 239000011521 glass Substances 0.000 claims description 4
- 230000037361 pathway Effects 0.000 claims description 4
- 229940049954 penicillin Drugs 0.000 claims description 4
- 229920002223 polystyrene Polymers 0.000 claims description 4
- 108020003175 receptors Proteins 0.000 claims description 4
- 102000005962 receptors Human genes 0.000 claims description 4
- 238000002702 ribosome display Methods 0.000 claims description 4
- 229940088597 hormone Drugs 0.000 claims description 3
- 239000005556 hormone Substances 0.000 claims description 3
- 102000040650 (ribonucleotides)n+m Human genes 0.000 claims description 2
- 108010012236 Chemokines Proteins 0.000 claims description 2
- 102000019034 Chemokines Human genes 0.000 claims description 2
- 102000053602 DNA Human genes 0.000 claims description 2
- 108090000189 Neuropeptides Proteins 0.000 claims description 2
- 102000003797 Neuropeptides Human genes 0.000 claims description 2
- 108010076504 Protein Sorting Signals Proteins 0.000 claims description 2
- 239000011543 agarose gel Substances 0.000 claims description 2
- 239000007791 liquid phase Substances 0.000 claims description 2
- 239000007790 solid phase Substances 0.000 claims description 2
- 102000055501 telomere Human genes 0.000 claims description 2
- 108091035539 telomere Proteins 0.000 claims description 2
- 210000003411 telomere Anatomy 0.000 claims description 2
- 230000009261 transgenic effect Effects 0.000 claims description 2
- 241000701959 Escherichia virus Lambda Species 0.000 claims 6
- 241000394658 Prymnesium kappa Species 0.000 claims 6
- 230000000692 anti-sense effect Effects 0.000 abstract description 10
- 239000000523 sample Substances 0.000 description 34
- 230000008569 process Effects 0.000 description 22
- -1 e.g. Proteins 0.000 description 21
- 238000013461 design Methods 0.000 description 20
- 239000013598 vector Substances 0.000 description 17
- 102000004169 proteins and genes Human genes 0.000 description 16
- 238000007834 ligase chain reaction Methods 0.000 description 14
- 238000004458 analytical method Methods 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 230000035772 mutation Effects 0.000 description 12
- 125000003275 alpha amino acid group Chemical group 0.000 description 11
- 230000004048 modification Effects 0.000 description 11
- 238000012986 modification Methods 0.000 description 11
- 108010066717 Q beta Replicase Proteins 0.000 description 10
- 239000000463 material Substances 0.000 description 9
- 239000013615 primer Substances 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 238000006467 substitution reaction Methods 0.000 description 9
- 238000010367 cloning Methods 0.000 description 8
- 230000028993 immune response Effects 0.000 description 8
- 238000000338 in vitro Methods 0.000 description 8
- 239000002253 acid Substances 0.000 description 7
- 238000009396 hybridization Methods 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 230000001404 mediated effect Effects 0.000 description 7
- 230000002459 sustained effect Effects 0.000 description 7
- 238000002965 ELISA Methods 0.000 description 6
- 206010028980 Neoplasm Diseases 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 230000002349 favourable effect Effects 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 230000002068 genetic effect Effects 0.000 description 6
- 238000002372 labelling Methods 0.000 description 6
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 6
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical compound CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 6
- 238000003127 radioimmunoassay Methods 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 238000004809 thin layer chromatography Methods 0.000 description 6
- 238000013519 translation Methods 0.000 description 6
- 229960005486 vaccine Drugs 0.000 description 6
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 5
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 5
- 238000007792 addition Methods 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000003471 mutagenic agent Substances 0.000 description 5
- 231100000707 mutagenic chemical Toxicity 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 108010042407 Endonucleases Proteins 0.000 description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- 108060003951 Immunoglobulin Proteins 0.000 description 4
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 4
- 108091092195 Intron Proteins 0.000 description 4
- IOVCWXUNBOPUCH-UHFFFAOYSA-N Nitrous acid Chemical compound ON=O IOVCWXUNBOPUCH-UHFFFAOYSA-N 0.000 description 4
- 241000700605 Viruses Species 0.000 description 4
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 4
- 238000003491 array Methods 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 239000002962 chemical mutagen Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 230000007547 defect Effects 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 238000012239 gene modification Methods 0.000 description 4
- 102000018358 immunoglobulin Human genes 0.000 description 4
- 108020004999 messenger RNA Proteins 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 150000004713 phosphodiesters Chemical class 0.000 description 4
- 239000002243 precursor Substances 0.000 description 4
- 230000009897 systematic effect Effects 0.000 description 4
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 4
- RNAMYOYQYRYFQY-UHFFFAOYSA-N 2-(4,4-difluoropiperidin-1-yl)-6-methoxy-n-(1-propan-2-ylpiperidin-4-yl)-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-amine Chemical compound N1=C(N2CCC(F)(F)CC2)N=C2C=C(OCCCN3CCCC3)C(OC)=CC2=C1NC1CCN(C(C)C)CC1 RNAMYOYQYRYFQY-UHFFFAOYSA-N 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- 108010013369 Enteropeptidase Proteins 0.000 description 3
- 102100029727 Enteropeptidase Human genes 0.000 description 3
- 241000238631 Hexapoda Species 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- 102000002278 Ribosomal Proteins Human genes 0.000 description 3
- 108010000605 Ribosomal Proteins Proteins 0.000 description 3
- 238000001042 affinity chromatography Methods 0.000 description 3
- 210000003719 b-lymphocyte Anatomy 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 238000002306 biochemical method Methods 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 238000004364 calculation method Methods 0.000 description 3
- 101150039352 can gene Proteins 0.000 description 3
- 238000005251 capillar electrophoresis Methods 0.000 description 3
- 210000000234 capsid Anatomy 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 238000001962 electrophoresis Methods 0.000 description 3
- 238000001502 gel electrophoresis Methods 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 230000001900 immune effect Effects 0.000 description 3
- 230000036039 immunity Effects 0.000 description 3
- 230000000951 immunodiffusion Effects 0.000 description 3
- 238000000760 immunoelectrophoresis Methods 0.000 description 3
- 238000011005 laboratory method Methods 0.000 description 3
- 230000005291 magnetic effect Effects 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 238000010369 molecular cloning Methods 0.000 description 3
- 238000000163 radioactive labelling Methods 0.000 description 3
- 238000002601 radiography Methods 0.000 description 3
- 238000003259 recombinant expression Methods 0.000 description 3
- 238000003345 scintillation counting Methods 0.000 description 3
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 238000002798 spectrophotometry method Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- PIINGYXNCHTJTF-UHFFFAOYSA-N 2-(2-azaniumylethylamino)acetate Chemical group NCCNCC(O)=O PIINGYXNCHTJTF-UHFFFAOYSA-N 0.000 description 2
- MWBWWFOAEOYUST-UHFFFAOYSA-N 2-aminopurine Chemical compound NC1=NC=C2N=CNC2=N1 MWBWWFOAEOYUST-UHFFFAOYSA-N 0.000 description 2
- WTLKTXIHIHFSGU-UHFFFAOYSA-N 2-nitrosoguanidine Chemical compound NC(N)=NN=O WTLKTXIHIHFSGU-UHFFFAOYSA-N 0.000 description 2
- KKAJSJJFBSOMGS-UHFFFAOYSA-N 3,6-diamino-10-methylacridinium chloride Chemical compound [Cl-].C1=C(N)C=C2[N+](C)=C(C=C(N)C=C3)C3=CC2=C1 KKAJSJJFBSOMGS-UHFFFAOYSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- LQLQRFGHAALLLE-UHFFFAOYSA-N 5-bromouracil Chemical compound BrC1=CNC(=O)NC1=O LQLQRFGHAALLLE-UHFFFAOYSA-N 0.000 description 2
- 102100033350 ATP-dependent translocase ABCB1 Human genes 0.000 description 2
- 108010032595 Antibody Binding Sites Proteins 0.000 description 2
- 108010078791 Carrier Proteins Proteins 0.000 description 2
- 108010035563 Chloramphenicol O-acetyltransferase Proteins 0.000 description 2
- 108700010070 Codon Usage Proteins 0.000 description 2
- 241000557626 Corvus corax Species 0.000 description 2
- 102000001996 DNA Polymerase beta Human genes 0.000 description 2
- 108010001132 DNA Polymerase beta Proteins 0.000 description 2
- 102000010719 DNA-(Apurinic or Apyrimidinic Site) Lyase Human genes 0.000 description 2
- 108010063362 DNA-(Apurinic or Apyrimidinic Site) Lyase Proteins 0.000 description 2
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 2
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 2
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 2
- 102100031780 Endonuclease Human genes 0.000 description 2
- 102000004533 Endonucleases Human genes 0.000 description 2
- 108010087819 Fc receptors Proteins 0.000 description 2
- 102000009109 Fc receptors Human genes 0.000 description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 2
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 2
- 108010047230 Member 1 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 description 2
- 229930192392 Mitomycin Natural products 0.000 description 2
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
- 101710163270 Nuclease Proteins 0.000 description 2
- 240000007594 Oryza sativa Species 0.000 description 2
- 235000007164 Oryza sativa Nutrition 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 108091093037 Peptide nucleic acid Proteins 0.000 description 2
- WDVSHHCDHLJJJR-UHFFFAOYSA-N Proflavine Chemical compound C1=CC(N)=CC2=NC3=CC(N)=CC=C3C=C21 WDVSHHCDHLJJJR-UHFFFAOYSA-N 0.000 description 2
- 108091028664 Ribonucleotide Proteins 0.000 description 2
- 241000589500 Thermus aquaticus Species 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 229940023020 acriflavine Drugs 0.000 description 2
- 238000001261 affinity purification Methods 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 210000004436 artificial bacterial chromosome Anatomy 0.000 description 2
- 210000001106 artificial yeast chromosome Anatomy 0.000 description 2
- OGBVRMYSNSKIEF-UHFFFAOYSA-L benzyl-dioxido-oxo-$l^{5}-phosphane Chemical compound [O-]P([O-])(=O)CC1=CC=CC=C1 OGBVRMYSNSKIEF-UHFFFAOYSA-L 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 239000005547 deoxyribonucleotide Substances 0.000 description 2
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- NAGJZTKCGNOGPW-UHFFFAOYSA-K dioxido-sulfanylidene-sulfido-$l^{5}-phosphane Chemical compound [O-]P([O-])([S-])=S NAGJZTKCGNOGPW-UHFFFAOYSA-K 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 238000013467 fragmentation Methods 0.000 description 2
- 238000006062 fragmentation reaction Methods 0.000 description 2
- 230000002363 herbicidal effect Effects 0.000 description 2
- 239000004009 herbicide Substances 0.000 description 2
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 2
- 229940072221 immunoglobulins Drugs 0.000 description 2
- 238000009169 immunotherapy Methods 0.000 description 2
- 239000000138 intercalating agent Substances 0.000 description 2
- 210000000723 mammalian artificial chromosome Anatomy 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 229960000901 mepacrine Drugs 0.000 description 2
- 150000002739 metals Chemical class 0.000 description 2
- 239000011859 microparticle Substances 0.000 description 2
- 229960004857 mitomycin Drugs 0.000 description 2
- XTGGILXPEMRCFM-UHFFFAOYSA-N morpholin-4-yl carbamate Chemical compound NC(=O)ON1CCOCC1 XTGGILXPEMRCFM-UHFFFAOYSA-N 0.000 description 2
- 230000005298 paramagnetic effect Effects 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 210000004180 plasmocyte Anatomy 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 2
- 229960000286 proflavine Drugs 0.000 description 2
- 230000016434 protein splicing Effects 0.000 description 2
- GPKJTRJOBQGKQK-UHFFFAOYSA-N quinacrine Chemical compound C1=C(OC)C=C2C(NC(C)CCCN(CC)CC)=C(C=CC(Cl)=C3)C3=NC2=C1 GPKJTRJOBQGKQK-UHFFFAOYSA-N 0.000 description 2
- 230000013120 recombinational repair Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000002336 ribonucleotide Substances 0.000 description 2
- 125000002652 ribonucleotide group Chemical group 0.000 description 2
- 235000009566 rice Nutrition 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 230000002103 transcriptional effect Effects 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- WYTZZXDRDKSJID-UHFFFAOYSA-N (3-aminopropyl)triethoxysilane Chemical compound CCO[Si](OCC)(OCC)CCCN WYTZZXDRDKSJID-UHFFFAOYSA-N 0.000 description 1
- ZBMRKNMTMPPMMK-UHFFFAOYSA-N 2-amino-4-[hydroxy(methyl)phosphoryl]butanoic acid;azane Chemical compound [NH4+].CP(O)(=O)CCC(N)C([O-])=O ZBMRKNMTMPPMMK-UHFFFAOYSA-N 0.000 description 1
- SJECZPVISLOESU-UHFFFAOYSA-N 3-trimethoxysilylpropan-1-amine Chemical compound CO[Si](OC)(OC)CCCN SJECZPVISLOESU-UHFFFAOYSA-N 0.000 description 1
- 101150036497 AEBP1 gene Proteins 0.000 description 1
- 208000035657 Abasia Diseases 0.000 description 1
- 108010053754 Aldehyde reductase Proteins 0.000 description 1
- 102100027265 Aldo-keto reductase family 1 member B1 Human genes 0.000 description 1
- 241000203069 Archaea Species 0.000 description 1
- JBRZTFJDHDCESZ-UHFFFAOYSA-N AsGa Chemical compound [As]#[Ga] JBRZTFJDHDCESZ-UHFFFAOYSA-N 0.000 description 1
- 102100026189 Beta-galactosidase Human genes 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- 108090000994 Catalytic RNA Proteins 0.000 description 1
- 102000053642 Catalytic RNA Human genes 0.000 description 1
- 102000007528 DNA Polymerase III Human genes 0.000 description 1
- 108010071146 DNA Polymerase III Proteins 0.000 description 1
- 108090000323 DNA Topoisomerases Proteins 0.000 description 1
- 102000003915 DNA Topoisomerases Human genes 0.000 description 1
- 108010078339 DNA alkyltransferase Proteins 0.000 description 1
- 108010065542 DNA topoisomerase V Proteins 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 108091006149 Electron carriers Proteins 0.000 description 1
- 108090000371 Esterases Proteins 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 108010074860 Factor Xa Proteins 0.000 description 1
- 229910001218 Gallium arsenide Inorganic materials 0.000 description 1
- 102000005720 Glutathione transferase Human genes 0.000 description 1
- 108010070675 Glutathione transferase Proteins 0.000 description 1
- 208000009889 Herpes Simplex Diseases 0.000 description 1
- 108091027305 Heteroduplex Proteins 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 108010044467 Isoenzymes Proteins 0.000 description 1
- 108010025815 Kanamycin Kinase Proteins 0.000 description 1
- 241000588915 Klebsiella aerogenes Species 0.000 description 1
- 108010074338 Lymphokines Proteins 0.000 description 1
- 102000008072 Lymphokines Human genes 0.000 description 1
- 241000252186 Misgurnus fossilis Species 0.000 description 1
- 229910003177 MnII Inorganic materials 0.000 description 1
- 102000004855 Multi drug resistance-associated proteins Human genes 0.000 description 1
- 108090001099 Multi drug resistance-associated proteins Proteins 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 108020004485 Nonsense Codon Proteins 0.000 description 1
- 108020004711 Nucleic Acid Probes Proteins 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 108091081548 Palindromic sequence Proteins 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 229920000297 Rayon Polymers 0.000 description 1
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 1
- 239000004965 Silica aerogel Substances 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 101710172711 Structural protein Proteins 0.000 description 1
- 206010042602 Supraventricular extrasystoles Diseases 0.000 description 1
- 230000024932 T cell mediated immunity Effects 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 102000002933 Thioredoxin Human genes 0.000 description 1
- 108010022394 Threonine synthase Proteins 0.000 description 1
- 102000006601 Thymidine Kinase Human genes 0.000 description 1
- 108020004440 Thymidine kinase Proteins 0.000 description 1
- 108700029229 Transcriptional Regulatory Elements Proteins 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 241000906064 Zeus faber Species 0.000 description 1
- 230000006229 amino acid addition Effects 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 102000006646 aminoglycoside phosphotransferase Human genes 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 210000004507 artificial chromosome Anatomy 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 230000007321 biological mechanism Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 108010083912 bleomycin N-acetyltransferase Proteins 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000005859 cell recognition Effects 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- 229960005091 chloramphenicol Drugs 0.000 description 1
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 1
- VJYIFXVZLXQVHO-UHFFFAOYSA-N chlorsulfuron Chemical compound COC1=NC(C)=NC(NC(=O)NS(=O)(=O)C=2C(=CC=CC=2)Cl)=N1 VJYIFXVZLXQVHO-UHFFFAOYSA-N 0.000 description 1
- 239000013599 cloning vector Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- 102000004419 dihydrofolate reductase Human genes 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 229940092559 enterobacter aerogenes Drugs 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000037433 frameshift Effects 0.000 description 1
- IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 description 1
- 229960002963 ganciclovir Drugs 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000000710 homodimer Substances 0.000 description 1
- 210000000688 human artificial chromosome Anatomy 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000005931 immune cell recruitment Effects 0.000 description 1
- 239000012642 immune effector Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 230000001024 immunotherapeutic effect Effects 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000000126 in silico method Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 239000004816 latex Substances 0.000 description 1
- 229920000126 latex Polymers 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 239000000696 magnetic material Substances 0.000 description 1
- 239000006249 magnetic particle Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229910052752 metalloid Inorganic materials 0.000 description 1
- 150000002738 metalloids Chemical class 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- ZAHQPTJLOCWVPG-UHFFFAOYSA-N mitoxantrone dihydrochloride Chemical compound Cl.Cl.O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO ZAHQPTJLOCWVPG-UHFFFAOYSA-N 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 239000002853 nucleic acid probe Substances 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- LPMXVESGRSUGHW-HBYQJFLCSA-N ouabain Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@@H]1C[C@@]2(O)CC[C@H]3[C@@]4(O)CC[C@H](C=5COC(=O)C=5)[C@@]4(C)C[C@@H](O)[C@@H]3[C@@]2(CO)[C@H](O)C1 LPMXVESGRSUGHW-HBYQJFLCSA-N 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920000139 polyethylene terephthalate Polymers 0.000 description 1
- 239000005020 polyethylene terephthalate Substances 0.000 description 1
- 229920002704 polyhistidine Polymers 0.000 description 1
- 229920000193 polymethacrylate Polymers 0.000 description 1
- 229920006324 polyoxymethylene Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 239000002987 primer (paints) Substances 0.000 description 1
- 230000012743 protein tagging Effects 0.000 description 1
- 239000010453 quartz Substances 0.000 description 1
- 239000002964 rayon Substances 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- 210000002955 secretory cell Anatomy 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910000077 silane Inorganic materials 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 241001223854 teleost fish Species 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 108060008226 thioredoxin Proteins 0.000 description 1
- 229940094937 thioredoxin Drugs 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 108700026220 vif Genes Proteins 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6806—Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Analytical Chemistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Peptides Or Proteins (AREA)
- Enzymes And Modification Thereof (AREA)
Applications Claiming Priority (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US34876102P | 2002-01-14 | 2002-01-14 | |
| US34876402P | 2002-01-14 | 2002-01-14 | |
| US34860902P | 2002-01-14 | 2002-01-14 | |
| US60/348,609 | 2002-01-14 | ||
| US60/348,761 | 2002-01-14 | ||
| US60/348,764 | 2002-01-14 | ||
| US10/077,474 | 2002-02-14 | ||
| US10/077,474 US6673552B2 (en) | 2002-01-14 | 2002-02-14 | Methods for purifying annealed double-stranded oligonucleotides lacking base pair mismatches or nucleotide gaps |
| PCT/US2003/001189 WO2003060084A2 (en) | 2002-01-14 | 2003-01-14 | Methods for making polynucleotides and purifying double-stranded polynucleotides |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2473434A1 true CA2473434A1 (en) | 2003-07-24 |
Family
ID=34658146
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002473434A Abandoned CA2473434A1 (en) | 2002-01-14 | 2003-01-14 | Methods for making polynucleotides and purifying double-stranded polynucleotides |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US20050130156A1 (https=) |
| EP (1) | EP1472373A4 (https=) |
| JP (1) | JP2005514927A (https=) |
| AU (1) | AU2003217207A1 (https=) |
| CA (1) | CA2473434A1 (https=) |
| WO (1) | WO2003060084A2 (https=) |
Families Citing this family (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7563600B2 (en) | 2002-09-12 | 2009-07-21 | Combimatrix Corporation | Microarray synthesis and assembly of gene-length polynucleotides |
| JP2008523786A (ja) * | 2004-10-18 | 2008-07-10 | コドン デバイシズ インコーポレイテッド | 高忠実度合成ポリヌクレオチドのアセンブリ方法 |
| US20070122817A1 (en) * | 2005-02-28 | 2007-05-31 | George Church | Methods for assembly of high fidelity synthetic polynucleotides |
| US20070231805A1 (en) * | 2006-03-31 | 2007-10-04 | Baynes Brian M | Nucleic acid assembly optimization using clamped mismatch binding proteins |
| US8053191B2 (en) | 2006-08-31 | 2011-11-08 | Westend Asset Clearinghouse Company, Llc | Iterative nucleic acid assembly using activation of vector-encoded traits |
| US9115352B2 (en) * | 2008-03-31 | 2015-08-25 | Sloning Biotechnology Gmbh | Method for the preparation of a nucleic acid library |
| US10207240B2 (en) | 2009-11-03 | 2019-02-19 | Gen9, Inc. | Methods and microfluidic devices for the manipulation of droplets in high fidelity polynucleotide assembly |
| WO2011066185A1 (en) | 2009-11-25 | 2011-06-03 | Gen9, Inc. | Microfluidic devices and methods for gene synthesis |
| WO2011085075A2 (en) | 2010-01-07 | 2011-07-14 | Gen9, Inc. | Assembly of high fidelity polynucleotides |
| WO2012064975A1 (en) | 2010-11-12 | 2012-05-18 | Gen9, Inc. | Protein arrays and methods of using and making the same |
| CN103502448B (zh) | 2010-11-12 | 2017-03-29 | Gen9股份有限公司 | 核酸合成的方法和设备 |
| CN103620032B (zh) * | 2010-12-31 | 2016-02-24 | 生物蛋白有限公司 | 抗体的快速人源化 |
| LT2944693T (lt) | 2011-08-26 | 2019-08-26 | Gen9, Inc. | Kompozicijos ir būdai, skirti nukleorūgščių didelio tikslumo sąrankai |
| US9150853B2 (en) | 2012-03-21 | 2015-10-06 | Gen9, Inc. | Methods for screening proteins using DNA encoded chemical libraries as templates for enzyme catalysis |
| CA2871505C (en) | 2012-04-24 | 2021-10-12 | Gen9, Inc. | Methods for sorting nucleic acids and multiplexed preparative in vitro cloning |
| IL236303B (en) | 2012-06-25 | 2022-07-01 | Gen9 Inc | Methods for high-throughput nucleic acid assembly and sequencing |
| SG11201600853UA (en) | 2013-08-05 | 2016-03-30 | Twist Bioscience Corp | De novo synthesized gene libraries |
| US10669304B2 (en) | 2015-02-04 | 2020-06-02 | Twist Bioscience Corporation | Methods and devices for de novo oligonucleic acid assembly |
| US9981239B2 (en) | 2015-04-21 | 2018-05-29 | Twist Bioscience Corporation | Devices and methods for oligonucleic acid library synthesis |
| EP3350314A4 (en) | 2015-09-18 | 2019-02-06 | Twist Bioscience Corporation | OLIGONUCLEIC ACID VARIANT LIBRARIES VARIANT AND SYNTHESIS THEREOF |
| KR102794025B1 (ko) | 2015-09-22 | 2025-04-09 | 트위스트 바이오사이언스 코포레이션 | 핵산 합성을 위한 가요성 기판 |
| US10417457B2 (en) | 2016-09-21 | 2019-09-17 | Twist Bioscience Corporation | Nucleic acid based data storage |
| EP4556433A3 (en) | 2017-02-22 | 2025-08-06 | Twist Bioscience Corporation | Nucleic acid based data storage |
| WO2018170169A1 (en) | 2017-03-15 | 2018-09-20 | Twist Bioscience Corporation | Variant libraries of the immunological synapse and synthesis thereof |
| WO2018231872A1 (en) | 2017-06-12 | 2018-12-20 | Twist Bioscience Corporation | Methods for seamless nucleic acid assembly |
| WO2018231864A1 (en) | 2017-06-12 | 2018-12-20 | Twist Bioscience Corporation | Methods for seamless nucleic acid assembly |
| US11407837B2 (en) | 2017-09-11 | 2022-08-09 | Twist Bioscience Corporation | GPCR binding proteins and synthesis thereof |
| CN111565834B (zh) | 2017-10-20 | 2022-08-26 | 特韦斯特生物科学公司 | 用于多核苷酸合成的加热的纳米孔 |
| KR102804057B1 (ko) | 2018-01-04 | 2025-05-07 | 트위스트 바이오사이언스 코포레이션 | Dna 기반 디지털 정보 저장 |
| CA3100739A1 (en) | 2018-05-18 | 2019-11-21 | Twist Bioscience Corporation | Polynucleotides, reagents, and methods for nucleic acid hybridization |
| WO2020139871A1 (en) | 2018-12-26 | 2020-07-02 | Twist Bioscience Corporation | Highly accurate de novo polynucleotide synthesis |
| JP2022522668A (ja) | 2019-02-26 | 2022-04-20 | ツイスト バイオサイエンス コーポレーション | 抗体を最適化するための変異体核酸ライブラリ |
| CN113766930B (zh) | 2019-02-26 | 2025-07-22 | 特韦斯特生物科学公司 | Glp1受体的变异核酸文库 |
| US11332738B2 (en) | 2019-06-21 | 2022-05-17 | Twist Bioscience Corporation | Barcode-based nucleic acid sequence assembly |
| JP2022548783A (ja) | 2019-09-23 | 2022-11-21 | ツイスト バイオサイエンス コーポレーション | 単一ドメイン抗体のバリアント核酸ライブラリー |
| EP4034566A4 (en) | 2019-09-23 | 2024-01-24 | Twist Bioscience Corporation | VARIANT NUCLEIC ACID BANKS FOR CRTH2 |
| BR112022011235A2 (pt) | 2019-12-09 | 2022-12-13 | Twist Bioscience Corp | Bibliotecas de variantes de ácido nucleico para receptores de adenosina |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5556750A (en) * | 1989-05-12 | 1996-09-17 | Duke University | Methods and kits for fractionating a population of DNA molecules based on the presence or absence of a base-pair mismatch utilizing mismatch repair systems |
| US5750335A (en) * | 1992-04-24 | 1998-05-12 | Massachusetts Institute Of Technology | Screening for genetic variation |
| US6027877A (en) * | 1993-11-04 | 2000-02-22 | Gene Check, Inc. | Use of immobilized mismatch binding protein for detection of mutations and polymorphisms, purification of amplified DNA samples and allele identification |
| US6294325B1 (en) * | 1996-07-05 | 2001-09-25 | The Mount Sinai School Of Medicine Of The City University Of New York | Cloning and expression of thermostable multi genes and proteins and uses thereof |
| AU5195398A (en) * | 1996-10-25 | 1998-05-15 | Advanced Research And Technology Institute, Inc. | Dna sequences encoding fusions of dna repair proteins and uses thereof |
| WO1999010369A1 (en) * | 1997-08-28 | 1999-03-04 | Thomas Jefferson University | Compositions, kits, and methods for effecting adenine nucleotide modulation of dna mismatch recognition proteins |
| US6033861A (en) * | 1997-11-19 | 2000-03-07 | Incyte Genetics, Inc. | Methods for obtaining nucleic acid containing a mutation |
| US6297010B1 (en) * | 1998-01-30 | 2001-10-02 | Genzyme Corporation | Method for detecting and identifying mutations |
| US7033781B1 (en) * | 1999-09-29 | 2006-04-25 | Diversa Corporation | Whole cell engineering by mutagenizing a substantial portion of a starting genome, combining mutations, and optionally repeating |
| US6365355B1 (en) * | 2000-03-28 | 2002-04-02 | The Regents Of The University Of California | Chimeric proteins for detection and quantitation of DNA mutations, DNA sequence variations, DNA damage and DNA mismatches |
| US6673552B2 (en) * | 2002-01-14 | 2004-01-06 | Diversa Corporation | Methods for purifying annealed double-stranded oligonucleotides lacking base pair mismatches or nucleotide gaps |
-
2003
- 2003-01-14 CA CA002473434A patent/CA2473434A1/en not_active Abandoned
- 2003-01-14 JP JP2003560171A patent/JP2005514927A/ja not_active Abandoned
- 2003-01-14 AU AU2003217207A patent/AU2003217207A1/en not_active Abandoned
- 2003-01-14 US US10/501,592 patent/US20050130156A1/en not_active Abandoned
- 2003-01-14 WO PCT/US2003/001189 patent/WO2003060084A2/en not_active Ceased
- 2003-01-14 EP EP03713244A patent/EP1472373A4/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| WO2003060084A2 (en) | 2003-07-24 |
| EP1472373A4 (en) | 2005-07-27 |
| JP2005514927A (ja) | 2005-05-26 |
| US20050130156A1 (en) | 2005-06-16 |
| WO2003060084A3 (en) | 2004-08-19 |
| EP1472373A2 (en) | 2004-11-03 |
| AU2003217207A1 (en) | 2003-07-30 |
| WO2003060084A9 (en) | 2004-04-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20050130156A1 (en) | Methods for making polynucleotides and purifying double-stranded polynucleotides | |
| US20040009498A1 (en) | Chimeric antigen binding molecules and methods for making and using them | |
| US20030215837A1 (en) | Methods for purifying double-stranded nucleic acids lacking base pair mismatches or nucleotide gaps | |
| US6673552B2 (en) | Methods for purifying annealed double-stranded oligonucleotides lacking base pair mismatches or nucleotide gaps | |
| US11584959B2 (en) | Compositions and methods for selection of nucleic acids | |
| CN114555802B (zh) | 单细胞分析 | |
| KR102475710B1 (ko) | 단일 세포 전체 게놈 라이브러리 및 이의 제조를 위한 조합 인덱싱 방법 | |
| US20220042090A1 (en) | PROGRAMMABLE RNA-TEMPLATED SEQUENCING BY LIGATION (rSBL) | |
| JP7058502B2 (ja) | ゲノム適用および治療適用のための、核酸分子のクローン複製および増幅のためのシステムおよび方法 | |
| KR102354422B1 (ko) | 대량 평행 서열분석을 위한 dna 라이브러리의 생성 방법 및 이를 위한 키트 | |
| CN109415758A (zh) | 使用含接头的经固定化的转座体进行的标签片段化 | |
| JP2004532038A (ja) | 新規抗原結合分子の治療、診断、予防、酵素、産業ならびに農業各分野への応用とそのための新規抗原結合分子の作製とスクリーニングの方法 | |
| WO2011049955A1 (en) | Deducing exon connectivity by rna-templated dna ligation/sequencing | |
| US20090136986A1 (en) | Methods and cells for creating functional diversity and uses thereof | |
| US20030219781A1 (en) | Compositions and methods for making polynucleotides by iterative assembly of codon building blocks | |
| EP3098324A1 (en) | Compositions and methods for preparing sequencing libraries | |
| WO2007136833A2 (en) | Methods and compositions for aptamer production and uses thereof | |
| US20220372566A1 (en) | Immune repertoire profiling by primer extension target enrichment | |
| US20250346951A1 (en) | Methods for amplifying polynucleotide sequences in situ | |
| US20220333178A1 (en) | Methods for improving nucleic acid cluster clonality | |
| EP4673563A2 (en) | Targeted spatial sequencing | |
| US20240229118A1 (en) | Controlled rolling circle amplification | |
| US20260125752A1 (en) | Methods and probes for detecting polynucleotide sequences in cells and tissues | |
| HK40063948A (en) | Systems and methods for clonal replication and amplification of nucleic acid molecules for genomic and therapeutic applications | |
| JP2025504146A (ja) | 免疫細胞受容体の配列決定方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |