CA3109755A1 - Synthesis of dna with improved yield - Google Patents
Synthesis of dna with improved yield Download PDFInfo
- Publication number
- CA3109755A1 CA3109755A1 CA3109755A CA3109755A CA3109755A1 CA 3109755 A1 CA3109755 A1 CA 3109755A1 CA 3109755 A CA3109755 A CA 3109755A CA 3109755 A CA3109755 A CA 3109755A CA 3109755 A1 CA3109755 A1 CA 3109755A1
- Authority
- CA
- Canada
- Prior art keywords
- dna
- salts
- cell
- nucleotide
- synthesis
- 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.)
- Pending
Links
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 73
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 54
- 125000003729 nucleotide group Chemical group 0.000 claims abstract description 231
- 238000000034 method Methods 0.000 claims abstract description 155
- 230000008569 process Effects 0.000 claims abstract description 127
- 239000002773 nucleotide Substances 0.000 claims abstract description 124
- 150000001768 cations Chemical class 0.000 claims abstract description 108
- 230000006820 DNA synthesis Effects 0.000 claims abstract description 93
- 230000002255 enzymatic effect Effects 0.000 claims abstract description 59
- 150000003839 salts Chemical class 0.000 claims description 120
- 239000011777 magnesium Substances 0.000 claims description 54
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 52
- 229910052749 magnesium Inorganic materials 0.000 claims description 52
- 239000011541 reaction mixture Substances 0.000 claims description 51
- 229910001415 sodium ion Inorganic materials 0.000 claims description 40
- 102000004190 Enzymes Human genes 0.000 claims description 39
- 108090000790 Enzymes Proteins 0.000 claims description 39
- 238000006073 displacement reaction Methods 0.000 claims description 39
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 claims description 34
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 34
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 claims description 33
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 claims description 33
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 30
- 239000011734 sodium Substances 0.000 claims description 30
- 229910052708 sodium Inorganic materials 0.000 claims description 29
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 28
- -1 lithium nucleotide salts Chemical class 0.000 claims description 20
- 229910052792 caesium Inorganic materials 0.000 claims description 19
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 claims description 18
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 14
- 102000009609 Pyrophosphatases Human genes 0.000 claims description 14
- 108010009413 Pyrophosphatases Proteins 0.000 claims description 14
- 229910052700 potassium Inorganic materials 0.000 claims description 14
- 239000006172 buffering agent Substances 0.000 claims description 13
- 230000002829 reductive effect Effects 0.000 claims description 13
- 239000011591 potassium Substances 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 10
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- 229910052751 metal Inorganic materials 0.000 claims description 8
- 239000002184 metal Substances 0.000 claims description 8
- 150000003863 ammonium salts Chemical class 0.000 claims description 7
- 229910001417 caesium ion Inorganic materials 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 5
- 239000006179 pH buffering agent Substances 0.000 claims description 5
- 229910052701 rubidium Inorganic materials 0.000 claims description 5
- 102000016559 DNA Primase Human genes 0.000 claims description 3
- 108010092681 DNA Primase Proteins 0.000 claims description 3
- 239000000908 ammonium hydroxide Substances 0.000 claims description 3
- 150000001793 charged compounds Polymers 0.000 claims description 3
- 229910052730 francium Inorganic materials 0.000 claims description 3
- KLMCZVJOEAUDNE-UHFFFAOYSA-N francium atom Chemical compound [Fr] KLMCZVJOEAUDNE-UHFFFAOYSA-N 0.000 claims description 3
- IGLNJRXAVVLDKE-UHFFFAOYSA-N rubidium atom Chemical compound [Rb] IGLNJRXAVVLDKE-UHFFFAOYSA-N 0.000 claims description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 2
- 229910052790 beryllium Inorganic materials 0.000 claims description 2
- ATBAMAFKBVZNFJ-UHFFFAOYSA-N beryllium atom Chemical compound [Be] ATBAMAFKBVZNFJ-UHFFFAOYSA-N 0.000 claims description 2
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- 239000011575 calcium Substances 0.000 claims description 2
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- 229910052712 strontium Inorganic materials 0.000 claims description 2
- CIOAGBVUUVVLOB-UHFFFAOYSA-N strontium atom Chemical compound [Sr] CIOAGBVUUVVLOB-UHFFFAOYSA-N 0.000 claims description 2
- 229910052723 transition metal Inorganic materials 0.000 claims description 2
- 150000003624 transition metals Chemical class 0.000 claims description 2
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- 239000011701 zinc Substances 0.000 claims description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 claims 1
- 108020004414 DNA Proteins 0.000 abstract description 233
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- 238000006243 chemical reaction Methods 0.000 abstract description 81
- 230000002349 favourable effect Effects 0.000 abstract 1
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- 238000003199 nucleic acid amplification method Methods 0.000 description 51
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- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 35
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- 239000000203 mixture Substances 0.000 description 28
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- 238000004925 denaturation Methods 0.000 description 11
- 230000036425 denaturation Effects 0.000 description 11
- 238000007792 addition Methods 0.000 description 10
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- 238000012545 processing Methods 0.000 description 10
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- 108020004707 nucleic acids Proteins 0.000 description 8
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- 230000004544 DNA amplification Effects 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- SUYVUBYJARFZHO-RRKCRQDMSA-N dATP Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 SUYVUBYJARFZHO-RRKCRQDMSA-N 0.000 description 7
- RGWHQCVHVJXOKC-SHYZEUOFSA-N dCTP Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO[P@](O)(=O)O[P@](O)(=O)OP(O)(O)=O)[C@@H](O)C1 RGWHQCVHVJXOKC-SHYZEUOFSA-N 0.000 description 7
- HAAZLUGHYHWQIW-KVQBGUIXSA-N dGTP Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 HAAZLUGHYHWQIW-KVQBGUIXSA-N 0.000 description 7
- NHVNXKFIZYSCEB-XLPZGREQSA-N dTTP Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C1 NHVNXKFIZYSCEB-XLPZGREQSA-N 0.000 description 7
- 238000010348 incorporation Methods 0.000 description 7
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- 239000013612 plasmid Substances 0.000 description 7
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- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 6
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- 241000894007 species Species 0.000 description 6
- 108020001019 DNA Primers Proteins 0.000 description 5
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- 108020004682 Single-Stranded DNA Proteins 0.000 description 5
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- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 5
- 235000011180 diphosphates Nutrition 0.000 description 5
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- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 3
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Classifications
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- 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
- C12Q1/6844—Nucleic acid amplification reactions
- C12Q1/6846—Common amplification features
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- 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
- C12Q1/6844—Nucleic acid amplification reactions
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P19/00—Preparation of compounds containing saccharide radicals
- C12P19/26—Preparation of nitrogen-containing carbohydrates
- C12P19/28—N-glycosides
- C12P19/30—Nucleotides
- C12P19/34—Polynucleotides, e.g. nucleic acids, oligoribonucleotides
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- 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
- C12Q2527/00—Reactions demanding special reaction conditions
- C12Q2527/125—Specific component of sample, medium or buffer
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- 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
- C12Q2527/00—Reactions demanding special reaction conditions
- C12Q2527/137—Concentration of a component of medium
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12Q2531/10—Reactions of nucleic acids characterised by the purpose being amplify/increase the copy number of target nucleic acid
- C12Q2531/125—Rolling circle
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- Proteomics, Peptides & Aminoacids (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB1813429.6 | 2018-08-17 | ||
| GBGB1813429.6A GB201813429D0 (en) | 2018-08-17 | 2018-08-17 | Synthesis of DNA with improved yield |
| PCT/GB2019/052307 WO2020035698A1 (en) | 2018-08-17 | 2019-08-16 | Synthesis of dna with improved yield |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3109755A1 true CA3109755A1 (en) | 2020-02-20 |
Family
ID=63668172
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3109755A Pending CA3109755A1 (en) | 2018-08-17 | 2019-08-16 | Synthesis of dna with improved yield |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US20210301312A1 (enExample) |
| EP (1) | EP3837382A1 (enExample) |
| JP (2) | JP7548581B2 (enExample) |
| KR (1) | KR20210084431A (enExample) |
| CN (1) | CN113056565A (enExample) |
| AU (1) | AU2019321778B2 (enExample) |
| BR (1) | BR112021002764A2 (enExample) |
| CA (1) | CA3109755A1 (enExample) |
| GB (1) | GB201813429D0 (enExample) |
| IL (1) | IL280817B2 (enExample) |
| MX (1) | MX2021001729A (enExample) |
| SG (1) | SG11202101548YA (enExample) |
| WO (1) | WO2020035698A1 (enExample) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB202002068D0 (en) * | 2020-02-14 | 2020-04-01 | Touchlight Ip Ltd | DNA synthesis yield improvements |
| GB202111742D0 (en) | 2021-08-16 | 2021-09-29 | Touchlight Ip Ltd | Improved process |
| US20250027107A1 (en) | 2021-10-18 | 2025-01-23 | Flagship Pioneering Innovations Vii, Llc | Dna compositions and related methods |
| GB202319998D0 (en) | 2023-12-22 | 2024-02-07 | Touchlight Ip Ltd | duplexing method |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8435774B2 (en) * | 2006-06-28 | 2013-05-07 | Qiagen Gmbh | Enhancing reactivation of thermostable reversibly inactivated enzymes |
| WO2012009206A2 (en) * | 2010-07-12 | 2012-01-19 | Pacific Biosciences Of California, Inc. | Sequencing reactions with alkali metal cations for pulse width control |
| CA2856304C (en) * | 2011-04-20 | 2017-05-16 | Mesa Tech International, Inc. | Oscillating amplification reaction for nucleic acids |
| WO2013101783A2 (en) * | 2011-12-30 | 2013-07-04 | Bio-Rad Laboratories, Inc. | Methods and compositions for performing nucleic acid amplification reactions |
| US9587263B2 (en) * | 2014-03-26 | 2017-03-07 | General Electric Company | Isothermal amplification under low salt condition |
| GB201415789D0 (en) * | 2014-09-05 | 2014-10-22 | Touchlight Genetics Ltd | Synthesis of DNA |
-
2018
- 2018-08-17 GB GBGB1813429.6A patent/GB201813429D0/en not_active Ceased
-
2019
- 2019-08-16 SG SG11202101548YA patent/SG11202101548YA/en unknown
- 2019-08-16 AU AU2019321778A patent/AU2019321778B2/en active Active
- 2019-08-16 IL IL280817A patent/IL280817B2/en unknown
- 2019-08-16 EP EP19755959.4A patent/EP3837382A1/en active Pending
- 2019-08-16 WO PCT/GB2019/052307 patent/WO2020035698A1/en not_active Ceased
- 2019-08-16 MX MX2021001729A patent/MX2021001729A/es unknown
- 2019-08-16 CN CN201980067811.4A patent/CN113056565A/zh active Pending
- 2019-08-16 KR KR1020217007998A patent/KR20210084431A/ko active Pending
- 2019-08-16 JP JP2021507969A patent/JP7548581B2/ja active Active
- 2019-08-16 BR BR112021002764-5A patent/BR112021002764A2/pt unknown
- 2019-08-16 CA CA3109755A patent/CA3109755A1/en active Pending
- 2019-08-16 US US17/268,721 patent/US20210301312A1/en not_active Abandoned
-
2024
- 2024-05-02 JP JP2024074647A patent/JP2024099814A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| US20210301312A1 (en) | 2021-09-30 |
| JP2024099814A (ja) | 2024-07-25 |
| WO2020035698A1 (en) | 2020-02-20 |
| JP2021534746A (ja) | 2021-12-16 |
| IL280817B2 (en) | 2025-08-01 |
| IL280817A (en) | 2021-04-29 |
| BR112021002764A2 (pt) | 2021-07-20 |
| AU2019321778B2 (en) | 2025-05-08 |
| JP7548581B2 (ja) | 2024-09-10 |
| GB201813429D0 (en) | 2018-10-03 |
| SG11202101548YA (en) | 2021-03-30 |
| AU2019321778A1 (en) | 2021-02-25 |
| EP3837382A1 (en) | 2021-06-23 |
| KR20210084431A (ko) | 2021-07-07 |
| CN113056565A (zh) | 2021-06-29 |
| MX2021001729A (es) | 2021-04-19 |
| IL280817B1 (en) | 2025-04-01 |
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