JP2010518832A - ベータ−２−ミクログロブリン遺伝子からのｄｎａ標的配列を切断するメガヌクレアーゼ変異型及びその使用 - Google Patents
ベータ−２−ミクログロブリン遺伝子からのｄｎａ標的配列を切断するメガヌクレアーゼ変異型及びその使用 Download PDFInfo
- Publication number
- JP2010518832A JP2010518832A JP2009550342A JP2009550342A JP2010518832A JP 2010518832 A JP2010518832 A JP 2010518832A JP 2009550342 A JP2009550342 A JP 2009550342A JP 2009550342 A JP2009550342 A JP 2009550342A JP 2010518832 A JP2010518832 A JP 2010518832A
- Authority
- JP
- Japan
- Prior art keywords
- beta
- sequence
- positions
- crei
- gene
- 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
- 108010081355 beta 2-Microglobulin Proteins 0.000 title claims abstract description 99
- 108010050663 endodeoxyribonuclease CreI Proteins 0.000 claims abstract description 165
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 100
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 54
- 238000006467 substitution reaction Methods 0.000 claims abstract description 40
- 241001465754 Metazoa Species 0.000 claims abstract description 32
- 102000015736 beta 2-Microglobulin Human genes 0.000 claims abstract description 22
- 230000009261 transgenic effect Effects 0.000 claims abstract description 16
- 230000001575 pathological effect Effects 0.000 claims abstract description 4
- 230000002265 prevention Effects 0.000 claims abstract description 4
- 108020004414 DNA Proteins 0.000 claims description 151
- 238000003776 cleavage reaction Methods 0.000 claims description 89
- 239000000178 monomer Substances 0.000 claims description 89
- 230000007017 scission Effects 0.000 claims description 88
- 239000013598 vector Substances 0.000 claims description 87
- 239000002773 nucleotide Substances 0.000 claims description 86
- 125000003729 nucleotide group Chemical group 0.000 claims description 85
- 210000004027 cell Anatomy 0.000 claims description 77
- 230000035772 mutation Effects 0.000 claims description 74
- 102220527593 Prostaglandin E synthase_R70S_mutation Human genes 0.000 claims description 67
- 238000000034 method Methods 0.000 claims description 44
- 102220556562 Delta and Notch-like epidermal growth factor-related receptor_Y33R_mutation Human genes 0.000 claims description 34
- 230000008685 targeting Effects 0.000 claims description 32
- 102000040430 polynucleotide Human genes 0.000 claims description 29
- 108091033319 polynucleotide Proteins 0.000 claims description 29
- 239000002157 polynucleotide Substances 0.000 claims description 29
- 150000001413 amino acids Chemical class 0.000 claims description 28
- 102220591832 Potassium voltage-gated channel subfamily B member 1_D75R_mutation Human genes 0.000 claims description 27
- 238000012216 screening Methods 0.000 claims description 23
- 102220556561 Delta and Notch-like epidermal growth factor-related receptor_Q44W_mutation Human genes 0.000 claims description 22
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 21
- 239000013604 expression vector Substances 0.000 claims description 20
- 239000003550 marker Substances 0.000 claims description 20
- 239000012634 fragment Substances 0.000 claims description 19
- 230000014509 gene expression Effects 0.000 claims description 19
- 239000000833 heterodimer Substances 0.000 claims description 19
- 230000000295 complement effect Effects 0.000 claims description 16
- 230000002441 reversible effect Effects 0.000 claims description 16
- 108700026244 Open Reading Frames Proteins 0.000 claims description 15
- 102220005406 rs28928875 Human genes 0.000 claims description 15
- 102220510130 Coagulation factor VIII_D75Y_mutation Human genes 0.000 claims description 14
- 108091026890 Coding region Proteins 0.000 claims description 14
- 230000007018 DNA scission Effects 0.000 claims description 12
- 102220569779 Pyridoxal-dependent decarboxylase domain-containing protein 1_S40Q_mutation Human genes 0.000 claims description 12
- 238000004519 manufacturing process Methods 0.000 claims description 12
- 230000027455 binding Effects 0.000 claims description 11
- 230000005030 transcription termination Effects 0.000 claims description 10
- 102220580831 Serine/threonine-protein kinase STK11_K96R_mutation Human genes 0.000 claims description 7
- 102220560339 Stromal cell-derived factor 1_Y33A_mutation Human genes 0.000 claims description 7
- 102200155456 rs35947557 Human genes 0.000 claims description 7
- 238000011144 upstream manufacturing Methods 0.000 claims description 7
- 102220485790 Destrin_S40R_mutation Human genes 0.000 claims description 6
- 102220606761 Gap junction beta-1 protein_N30V_mutation Human genes 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 6
- 102220160907 rs886062986 Human genes 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 229910052700 potassium Inorganic materials 0.000 claims description 5
- 238000002054 transplantation Methods 0.000 claims description 5
- 102220548720 Delta and Notch-like epidermal growth factor-related receptor_Q38A_mutation Human genes 0.000 claims description 4
- 101000937544 Homo sapiens Beta-2-microglobulin Proteins 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 210000003734 kidney Anatomy 0.000 claims description 4
- 102220289727 rs1253463092 Human genes 0.000 claims description 4
- 230000001225 therapeutic effect Effects 0.000 claims description 4
- 230000035897 transcription Effects 0.000 claims description 4
- 238000013518 transcription Methods 0.000 claims description 4
- 229910052727 yttrium Inorganic materials 0.000 claims description 4
- 102220476563 NF-kappa-B inhibitor alpha_S32A_mutation Human genes 0.000 claims description 3
- 102220476565 NF-kappa-B inhibitor alpha_S32T_mutation Human genes 0.000 claims description 3
- 102220527083 Procollagen C-endopeptidase enhancer 1_D75S_mutation Human genes 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 210000000496 pancreas Anatomy 0.000 claims description 3
- 102220556550 Delta and Notch-like epidermal growth factor-related receptor_R68A_mutation Human genes 0.000 claims description 2
- 102220576068 HLA class I histocompatibility antigen, B alpha chain_Y33D_mutation Human genes 0.000 claims description 2
- 102220617997 Phenylalanine-4-hydroxylase_R68S_mutation Human genes 0.000 claims description 2
- 102220577261 Stromal cell-derived factor 1_R68E_mutation Human genes 0.000 claims description 2
- 229910052698 phosphorus Inorganic materials 0.000 claims description 2
- 102220017736 rs137854215 Human genes 0.000 claims description 2
- 102220005407 rs28928875 Human genes 0.000 claims description 2
- 102220079853 rs797045893 Human genes 0.000 claims description 2
- 229910052720 vanadium Inorganic materials 0.000 claims description 2
- 102220014375 rs397517056 Human genes 0.000 claims 5
- 102220558444 Proteinase-activated receptor 2_N30A_mutation Human genes 0.000 claims 2
- 102220195310 rs1057517867 Human genes 0.000 claims 2
- 102200081526 rs121913583 Human genes 0.000 claims 2
- 102220634135 Cystatin-A_D75E_mutation Human genes 0.000 claims 1
- 102220577259 Stromal cell-derived factor 1_R68Q_mutation Human genes 0.000 claims 1
- 210000002064 heart cell Anatomy 0.000 claims 1
- 210000000663 muscle cell Anatomy 0.000 claims 1
- 102220225706 rs1014627144 Human genes 0.000 claims 1
- 235000018102 proteins Nutrition 0.000 description 52
- 150000007523 nucleic acids Chemical class 0.000 description 44
- 102000039446 nucleic acids Human genes 0.000 description 43
- 108020004707 nucleic acids Proteins 0.000 description 43
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 41
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 36
- 108010042407 Endonucleases Proteins 0.000 description 34
- 102000004533 Endonucleases Human genes 0.000 description 34
- 230000005782 double-strand break Effects 0.000 description 26
- 235000001014 amino acid Nutrition 0.000 description 25
- 229940024606 amino acid Drugs 0.000 description 25
- 230000000694 effects Effects 0.000 description 19
- 231100000350 mutagenesis Toxicity 0.000 description 19
- 238000002703 mutagenesis Methods 0.000 description 18
- 230000008439 repair process Effects 0.000 description 18
- 102000004196 processed proteins & peptides Human genes 0.000 description 15
- 238000002744 homologous recombination Methods 0.000 description 14
- 230000006801 homologous recombination Effects 0.000 description 14
- 238000003556 assay Methods 0.000 description 12
- 238000003780 insertion Methods 0.000 description 12
- 230000037431 insertion Effects 0.000 description 12
- 229920001184 polypeptide Polymers 0.000 description 12
- 101100437218 Homo sapiens B2M gene Proteins 0.000 description 11
- 108091081548 Palindromic sequence Proteins 0.000 description 11
- 230000002779 inactivation Effects 0.000 description 11
- 238000013459 approach Methods 0.000 description 10
- 102220369054 c.94A>G Human genes 0.000 description 10
- 230000013011 mating Effects 0.000 description 10
- 230000006798 recombination Effects 0.000 description 10
- 238000005215 recombination Methods 0.000 description 10
- 102220101373 rs878854666 Human genes 0.000 description 10
- 238000012163 sequencing technique Methods 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 230000004186 co-expression Effects 0.000 description 9
- 238000012217 deletion Methods 0.000 description 9
- 230000037430 deletion Effects 0.000 description 9
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 8
- 210000004899 c-terminal region Anatomy 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 238000001727 in vivo Methods 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 230000006780 non-homologous end joining Effects 0.000 description 8
- 238000002708 random mutagenesis Methods 0.000 description 8
- 210000000130 stem cell Anatomy 0.000 description 8
- 239000004475 Arginine Substances 0.000 description 7
- 241000700605 Viruses Species 0.000 description 7
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 7
- 230000001939 inductive effect Effects 0.000 description 7
- 210000001161 mammalian embryo Anatomy 0.000 description 7
- 239000013612 plasmid Substances 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- 230000004568 DNA-binding Effects 0.000 description 6
- 241000196324 Embryophyta Species 0.000 description 6
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 6
- 102220476113 Vacuolar protein sorting-associated protein 33A_K28R_mutation Human genes 0.000 description 6
- 239000013611 chromosomal DNA Substances 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 238000010363 gene targeting Methods 0.000 description 6
- 229930027917 kanamycin Natural products 0.000 description 6
- 229960000318 kanamycin Drugs 0.000 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 description 6
- 229930182823 kanamycin A Natural products 0.000 description 6
- 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 6
- 210000004962 mammalian cell Anatomy 0.000 description 6
- 239000013641 positive control Substances 0.000 description 6
- 230000009466 transformation Effects 0.000 description 6
- 108700024394 Exon Proteins 0.000 description 5
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 5
- 229910009891 LiAc Inorganic materials 0.000 description 5
- 241000124008 Mammalia Species 0.000 description 5
- 108700008625 Reporter Genes Proteins 0.000 description 5
- 230000002378 acidificating effect Effects 0.000 description 5
- 230000003197 catalytic effect Effects 0.000 description 5
- 230000002759 chromosomal effect Effects 0.000 description 5
- 235000013922 glutamic acid Nutrition 0.000 description 5
- 239000004220 glutamic acid Substances 0.000 description 5
- 239000000710 homodimer Substances 0.000 description 5
- 210000005260 human cell Anatomy 0.000 description 5
- 239000011159 matrix material Substances 0.000 description 5
- 102200052872 rs118203897 Human genes 0.000 description 5
- 102220005171 rs33914359 Human genes 0.000 description 5
- 229910052717 sulfur Inorganic materials 0.000 description 5
- 229920000936 Agarose Polymers 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 108010091358 Hypoxanthine Phosphoribosyltransferase Proteins 0.000 description 4
- 101710163270 Nuclease Proteins 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 4
- 238000012790 confirmation Methods 0.000 description 4
- 238000010276 construction Methods 0.000 description 4
- 230000029087 digestion Effects 0.000 description 4
- 230000004927 fusion Effects 0.000 description 4
- 229930182830 galactose Natural products 0.000 description 4
- 230000003902 lesion Effects 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 239000013642 negative control Substances 0.000 description 4
- 210000004940 nucleus Anatomy 0.000 description 4
- 230000037361 pathway Effects 0.000 description 4
- 229920001451 polypropylene glycol Polymers 0.000 description 4
- 239000002243 precursor Substances 0.000 description 4
- 230000010076 replication Effects 0.000 description 4
- 102220280971 rs1253463092 Human genes 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 210000005253 yeast cell Anatomy 0.000 description 4
- BUZOGVVQWCXXDP-VPENINKCSA-N 8-oxo-dGTP Chemical compound O=C1NC=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 BUZOGVVQWCXXDP-VPENINKCSA-N 0.000 description 3
- 108700028369 Alleles Proteins 0.000 description 3
- 101150076800 B2M gene Proteins 0.000 description 3
- 102100026189 Beta-galactosidase Human genes 0.000 description 3
- 102000053602 DNA Human genes 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 102000018251 Hypoxanthine Phosphoribosyltransferase Human genes 0.000 description 3
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 3
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 3
- 239000004472 Lysine Substances 0.000 description 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
- 102000043129 MHC class I family Human genes 0.000 description 3
- 108091054437 MHC class I family Proteins 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 238000012408 PCR amplification Methods 0.000 description 3
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 3
- 101710185494 Zinc finger protein Proteins 0.000 description 3
- 102100023597 Zinc finger protein 816 Human genes 0.000 description 3
- 125000000539 amino acid group Chemical group 0.000 description 3
- 108010005774 beta-Galactosidase Proteins 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 210000000349 chromosome Anatomy 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 230000002950 deficient Effects 0.000 description 3
- 210000003527 eukaryotic cell Anatomy 0.000 description 3
- 238000001415 gene therapy Methods 0.000 description 3
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 3
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 210000001082 somatic cell Anatomy 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- OPIFSICVWOWJMJ-AEOCFKNESA-N 5-bromo-4-chloro-3-indolyl beta-D-galactoside Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1OC1=CNC2=CC=C(Br)C(Cl)=C12 OPIFSICVWOWJMJ-AEOCFKNESA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
- 241000271566 Aves Species 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 108091092195 Intron Proteins 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 239000004677 Nylon Substances 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 229920002873 Polyethylenimine Polymers 0.000 description 2
- 108010072866 Prostate-Specific Antigen Proteins 0.000 description 2
- 102100038358 Prostate-specific antigen Human genes 0.000 description 2
- 102220471762 Proteasome subunit alpha type-7_K28A_mutation Human genes 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
- 241000700584 Simplexvirus Species 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- 206010052779 Transplant rejections Diseases 0.000 description 2
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 2
- 102220533129 WW domain-containing oxidoreductase_K28T_mutation Human genes 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 206010002022 amyloidosis Diseases 0.000 description 2
- 210000004102 animal cell Anatomy 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 2
- 235000009582 asparagine Nutrition 0.000 description 2
- 229960001230 asparagine Drugs 0.000 description 2
- 102220369055 c.96C>G Human genes 0.000 description 2
- 238000002659 cell therapy Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 238000012761 co-transfection Methods 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 230000011559 double-strand break repair via nonhomologous end joining Effects 0.000 description 2
- 241001493065 dsRNA viruses Species 0.000 description 2
- 210000002257 embryonic structure Anatomy 0.000 description 2
- 231100000221 frame shift mutation induction Toxicity 0.000 description 2
- 230000037433 frameshift Effects 0.000 description 2
- 108020001507 fusion proteins Proteins 0.000 description 2
- 102000037865 fusion proteins Human genes 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 230000035876 healing Effects 0.000 description 2
- 210000002216 heart Anatomy 0.000 description 2
- 230000008105 immune reaction Effects 0.000 description 2
- 230000002163 immunogen Effects 0.000 description 2
- 230000000415 inactivating effect Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 2
- 150000002614 leucines Chemical group 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 229920001778 nylon Polymers 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000007320 rich medium Substances 0.000 description 2
- 102200108088 rs1555526742 Human genes 0.000 description 2
- 102220131518 rs201347216 Human genes 0.000 description 2
- 102220082053 rs201520438 Human genes 0.000 description 2
- 102220056952 rs730880947 Human genes 0.000 description 2
- 102220095173 rs756946899 Human genes 0.000 description 2
- 102220262471 rs767354237 Human genes 0.000 description 2
- 239000012064 sodium phosphate buffer Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical group CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
- 241000701161 unidentified adenovirus Species 0.000 description 2
- 241001430294 unidentified retrovirus Species 0.000 description 2
- 239000013603 viral vector Substances 0.000 description 2
- DIGQNXIGRZPYDK-WKSCXVIASA-N (2R)-6-amino-2-[[2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-[[(2R,3S)-2-[[2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S,3S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2R)-2-[[2-[[2-[[2-[(2-amino-1-hydroxyethylidene)amino]-3-carboxy-1-hydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1,5-dihydroxy-5-iminopentylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]hexanoic acid Chemical compound C[C@@H]([C@@H](C(=N[C@@H](CS)C(=N[C@@H](C)C(=N[C@@H](CO)C(=NCC(=N[C@@H](CCC(=N)O)C(=NC(CS)C(=N[C@H]([C@H](C)O)C(=N[C@H](CS)C(=N[C@H](CO)C(=NCC(=N[C@H](CS)C(=NCC(=N[C@H](CCCCN)C(=O)O)O)O)O)O)O)O)O)O)O)O)O)O)O)N=C([C@H](CS)N=C([C@H](CO)N=C([C@H](CO)N=C([C@H](C)N=C(CN=C([C@H](CO)N=C([C@H](CS)N=C(CN=C(C(CS)N=C(C(CC(=O)O)N=C(CN)O)O)O)O)O)O)O)O)O)O)O)O DIGQNXIGRZPYDK-WKSCXVIASA-N 0.000 description 1
- 230000006269 (delayed) early viral mRNA transcription Effects 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 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
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 description 1
- 102220560627 ATP-binding cassette sub-family C member 8_S38A_mutation Human genes 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 102000055025 Adenosine deaminases Human genes 0.000 description 1
- 241000710929 Alphavirus Species 0.000 description 1
- 102000009091 Amyloidogenic Proteins Human genes 0.000 description 1
- 108010048112 Amyloidogenic Proteins Proteins 0.000 description 1
- 102220488155 Bone morphogenetic protein receptor type-2_Q92L_mutation Human genes 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 102220600549 C-C chemokine receptor type 5_S40D_mutation Human genes 0.000 description 1
- 101710167800 Capsid assembly scaffolding protein Proteins 0.000 description 1
- 102000011632 Caseins Human genes 0.000 description 1
- 108010076119 Caseins Proteins 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 108020004638 Circular DNA Proteins 0.000 description 1
- 108091028075 Circular RNA Proteins 0.000 description 1
- 102220510142 Coagulation factor VIII_D75E_mutation Human genes 0.000 description 1
- 241000711573 Coronaviridae Species 0.000 description 1
- 241000938605 Crocodylia Species 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- 230000005778 DNA damage Effects 0.000 description 1
- 231100000277 DNA damage Toxicity 0.000 description 1
- 238000012270 DNA recombination Methods 0.000 description 1
- 241000450599 DNA viruses Species 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 102220476893 Developmental pluripotency-associated protein 3_S33G_mutation Human genes 0.000 description 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- 101100162704 Emericella nidulans I-AniI gene Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000289695 Eutheria Species 0.000 description 1
- 108091029865 Exogenous DNA Proteins 0.000 description 1
- 241000710831 Flavivirus Species 0.000 description 1
- 208000000666 Fowlpox Diseases 0.000 description 1
- 102220576563 HLA class I histocompatibility antigen, A alpha chain_R68K_mutation Human genes 0.000 description 1
- 101710197836 HLA class I histocompatibility antigen, alpha chain G Proteins 0.000 description 1
- 102220466851 HLA class II histocompatibility antigen, DR beta 4 chain_V59A_mutation Human genes 0.000 description 1
- 101100467529 Homo sapiens RAG1 gene Proteins 0.000 description 1
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 108010025815 Kanamycin Kinase Proteins 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 241000713666 Lentivirus Species 0.000 description 1
- 102000043131 MHC class II family Human genes 0.000 description 1
- 108091054438 MHC class II family Proteins 0.000 description 1
- 108010059343 MM Form Creatine Kinase Proteins 0.000 description 1
- 241000701076 Macacine alphaherpesvirus 1 Species 0.000 description 1
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 1
- 201000005505 Measles Diseases 0.000 description 1
- 102000003939 Membrane transport proteins Human genes 0.000 description 1
- 108090000301 Membrane transport proteins Proteins 0.000 description 1
- 102000003792 Metallothionein Human genes 0.000 description 1
- 108090000157 Metallothionein Proteins 0.000 description 1
- 108700005084 Multigene Family Proteins 0.000 description 1
- PYUSHNKNPOHWEZ-YFKPBYRVSA-N N-formyl-L-methionine Chemical compound CSCC[C@@H](C(O)=O)NC=O PYUSHNKNPOHWEZ-YFKPBYRVSA-N 0.000 description 1
- 230000006051 NK cell activation Effects 0.000 description 1
- 102220574984 Neuronal acetylcholine receptor subunit alpha-2_V73I_mutation Human genes 0.000 description 1
- 241000714209 Norwalk virus Species 0.000 description 1
- 108010077850 Nuclear Localization Signals Proteins 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 241000709664 Picornaviridae Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 108010071690 Prealbumin Proteins 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 101710130420 Probable capsid assembly scaffolding protein Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 102220526774 Protein MTSS 1_D56E_mutation Human genes 0.000 description 1
- 102220537299 Protein NDRG2_N30R_mutation Human genes 0.000 description 1
- 102220620962 Protein pitchfork_P83A_mutation Human genes 0.000 description 1
- 241000125945 Protoparvovirus Species 0.000 description 1
- 206010037742 Rabies Diseases 0.000 description 1
- 241000711798 Rabies lyssavirus Species 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 241000702263 Reovirus sp. Species 0.000 description 1
- 241000712907 Retroviridae Species 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 101710204410 Scaffold protein Proteins 0.000 description 1
- 108091081021 Sense strand Proteins 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 102100032491 Serine protease 1 Human genes 0.000 description 1
- 102220528881 Serum amyloid A-4 protein_I24F_mutation Human genes 0.000 description 1
- 241000713675 Spumavirus Species 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 102220602177 Synaptotagmin-3_F54A_mutation Human genes 0.000 description 1
- 239000004098 Tetracycline Substances 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
- 102100029290 Transthyretin Human genes 0.000 description 1
- 102220585944 Transthyretin_S72P_mutation Human genes 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 108091023045 Untranslated Region Proteins 0.000 description 1
- 206010046865 Vaccinia virus infection Diseases 0.000 description 1
- 241000711975 Vesicular stomatitis virus Species 0.000 description 1
- 108010046377 Whey Proteins Proteins 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- 230000003942 amyloidogenic effect Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- -1 aromatic amino acid Chemical class 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 102220362486 c.167A>G Human genes 0.000 description 1
- 102220347825 c.207C>G Human genes 0.000 description 1
- 102220414144 c.275A>G Human genes 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 102000004419 dihydrofolate reductase Human genes 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000003255 drug test Methods 0.000 description 1
- 235000013601 eggs Nutrition 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 238000010304 firing Methods 0.000 description 1
- 238000003198 gene knock in Methods 0.000 description 1
- 238000003209 gene knockout Methods 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 description 1
- 102000005396 glutamine synthetase Human genes 0.000 description 1
- 108020002326 glutamine synthetase Proteins 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000001631 haemodialysis Methods 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 230000000322 hemodialysis Effects 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 238000013537 high throughput screening Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 108010002685 hygromycin-B kinase Proteins 0.000 description 1
- 210000001822 immobilized cell Anatomy 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000000984 immunochemical effect Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000017730 intein-mediated protein splicing Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000009878 intermolecular interaction Effects 0.000 description 1
- 210000004153 islets of langerhan Anatomy 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 238000011819 knockout animal model Methods 0.000 description 1
- 101150066555 lacZ gene Proteins 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000021121 meiosis Effects 0.000 description 1
- 230000009061 membrane transport Effects 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 238000007899 nucleic acid hybridization Methods 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 108010085336 phosphoribosyl-AMP cyclohydrolase Proteins 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 230000003169 placental effect Effects 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 229920002704 polyhistidine Polymers 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 230000016434 protein splicing Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002213 purine nucleotide Substances 0.000 description 1
- 239000002719 pyrimidine nucleotide Substances 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 229960001225 rifampicin Drugs 0.000 description 1
- JQXXHWHPUNPDRT-WLSIYKJHSA-N rifampicin Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(C)/C(=O)NC=2C(O)=C3C([O-])=C4C)C)OC)C4=C1C3=C(O)C=2\C=N\N1CC[NH+](C)CC1 JQXXHWHPUNPDRT-WLSIYKJHSA-N 0.000 description 1
- 102220223852 rs1060502978 Human genes 0.000 description 1
- 102220218299 rs1060503484 Human genes 0.000 description 1
- 102220232576 rs1085307646 Human genes 0.000 description 1
- 102220235661 rs1131691837 Human genes 0.000 description 1
- 102220156594 rs116793431 Human genes 0.000 description 1
- 102200080006 rs118204447 Human genes 0.000 description 1
- 102220014106 rs142059019 Human genes 0.000 description 1
- 102200144532 rs142951029 Human genes 0.000 description 1
- 102220256808 rs149398412 Human genes 0.000 description 1
- 102220279096 rs1554888137 Human genes 0.000 description 1
- 102220340175 rs1555191568 Human genes 0.000 description 1
- 102220050493 rs193921030 Human genes 0.000 description 1
- 102200029475 rs200313585 Human genes 0.000 description 1
- 102220125357 rs201745474 Human genes 0.000 description 1
- 102220005504 rs281860657 Human genes 0.000 description 1
- 102200082929 rs33924146 Human genes 0.000 description 1
- 102200127556 rs34159654 Human genes 0.000 description 1
- 102200091373 rs387906668 Human genes 0.000 description 1
- 102220022283 rs397509331 Human genes 0.000 description 1
- 102220093874 rs558707786 Human genes 0.000 description 1
- 102200123508 rs572237881 Human genes 0.000 description 1
- 102200006402 rs587778189 Human genes 0.000 description 1
- 102220044643 rs587781450 Human genes 0.000 description 1
- 102200025917 rs72547556 Human genes 0.000 description 1
- 102220056650 rs730881057 Human genes 0.000 description 1
- 102220067424 rs757120802 Human genes 0.000 description 1
- 102220261990 rs776085350 Human genes 0.000 description 1
- 102220070981 rs794728706 Human genes 0.000 description 1
- 102220100613 rs878854772 Human genes 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 239000012096 transfection reagent Substances 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 208000007089 vaccinia Diseases 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 108700026220 vif Genes Proteins 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 235000021247 β-casein Nutrition 0.000 description 1
Images
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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
- C12N9/22—Ribonucleases RNAses, DNAses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Biomedical Technology (AREA)
- General Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- General Chemical & Material Sciences (AREA)
- Biotechnology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Plant Pathology (AREA)
- Urology & Nephrology (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Transplantation (AREA)
- Neurology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Enzymes And Modification Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Breeding Of Plants And Reproduction By Means Of Culturing (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/IB2007/001532 WO2008102199A1 (fr) | 2007-02-20 | 2007-02-20 | Variants de méganucléase clivant une séquence cible d'adn provenant du gène de la bêta-2-microglobuline et utilisations de ceux-ci |
| PCT/IB2008/001334 WO2008102274A2 (fr) | 2007-02-20 | 2008-02-20 | Variants de méganucléase clivant une séquence d'adn cible du gène de la bêta-2-microglobuline et leurs utilisations |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2010518832A true JP2010518832A (ja) | 2010-06-03 |
Family
ID=39167465
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009550342A Pending JP2010518832A (ja) | 2007-02-20 | 2008-02-20 | ベータ−２−ミクログロブリン遺伝子からのｄｎａ標的配列を切断するメガヌクレアーゼ変異型及びその使用 |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP2121036A2 (fr) |
| JP (1) | JP2010518832A (fr) |
| CN (1) | CN101678126A (fr) |
| AU (1) | AU2008218605A1 (fr) |
| CA (1) | CA2678709A1 (fr) |
| WO (2) | WO2008102199A1 (fr) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2017508468A (ja) * | 2014-03-11 | 2017-03-30 | セレクティスＣｅｌｌｅｃｔｉｓ | 同種移植に適合するｔ細胞を作製するための方法 |
| JP2018538000A (ja) * | 2015-12-23 | 2018-12-27 | プレシジョン バイオサイエンシズ，インク． | ヒトβ−２ミクログロブリン遺伝子に見られる認識配列を有する操作されたメガヌクレアーゼ |
| JP2022101530A (ja) * | 2015-06-30 | 2022-07-06 | セレクティス | 特異的エンドヌクレアーゼを使用した遺伝子不活化によってｎｋ細胞の機能性を改善する方法 |
Families Citing this family (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2704383A1 (fr) | 2007-10-31 | 2009-05-07 | James Jefferson Smith | Meganucleases monocatenaires concues rationnellement contenant des sequences de reconnaissance non palindromiques |
| WO2009114321A2 (fr) | 2008-03-11 | 2009-09-17 | Precision Biosciencs, Inc. | Méganucléases rationnellement conçues pour modification par génie génétique du génome du maïs |
| EP4001408A3 (fr) | 2008-07-14 | 2022-06-08 | Precision Biosciences, Inc. | Séquences de reconnaissance de méganucléases dérivées d'i-crei et utilisations associées |
| US9273296B2 (en) * | 2008-09-08 | 2016-03-01 | Cellectis | Meganuclease variants cleaving a DNA target sequence from a glutamine synthetase gene and uses thereof |
| WO2010122367A2 (fr) * | 2009-04-21 | 2010-10-28 | Cellectis | Variants de méganucléases coupant l'insertion génomique d'un virus et applications associées |
| WO2010136981A2 (fr) | 2009-05-26 | 2010-12-02 | Cellectis | Variants de méganucléase clivant le génome d'un virus non intégratif pathogène et leurs utilisations |
| WO2010136841A2 (fr) * | 2009-05-26 | 2010-12-02 | Cellectis | Variants de méganucléase clivant le génome d'un virus à intégration non génomique et leurs utilisations |
| WO2011007193A1 (fr) | 2009-07-17 | 2011-01-20 | Cellectis | Vecteurs viraux codant pour une matrice de réparation d'adn et contenant une méganucléase spécifique de site associée à un virion pour un ciblage de gène |
| WO2011021062A1 (fr) | 2009-08-21 | 2011-02-24 | Cellectis | Variants de méganucléase clivant une séquence dadn cible du gène dacide lysosomique alpha-glucosidase humain et utilisations de ceux-ci |
| EP2569424A1 (fr) | 2010-05-12 | 2013-03-20 | Cellectis | Variants de méganucléase clivant une séquence cible d'adn du gène de dystrophine et leurs utilisations |
| US20130183282A1 (en) | 2010-05-12 | 2013-07-18 | Cellectis | Meganuclease variants cleaving a DNA target sequence from the rhodopsin gene and uses thereof |
| CN103119169B (zh) | 2010-06-09 | 2018-11-20 | 拜尔作物科学公司 | 植物基因组改造中常用的在核苷酸序列上修饰植物基因组的方法和工具 |
| WO2011154158A1 (fr) * | 2010-06-09 | 2011-12-15 | Bayer Bioscience N.V. | Procédés et moyens pour modifier un génome végétal au niveau d'une séquence nucléotidique habituellement utilisée dans l'ingénierie des génomes végétaux |
| EP2582845A2 (fr) | 2010-06-15 | 2013-04-24 | Cellectis | Procédé permettant d'améliorer le clivage d'un adn par une endonucléase sensible à la méthylation |
| US20130189759A1 (en) | 2010-07-07 | 2013-07-25 | Cellectis | Meganucleases variants cleaving a dna target sequence in the nanog gene and uses thereof |
| WO2012010976A2 (fr) | 2010-07-15 | 2012-01-26 | Cellectis | Variants de méganucléases clivant une séquence d'adn cible dans le gène tert et leurs utilisations |
| WO2012007848A2 (fr) | 2010-07-16 | 2012-01-19 | Cellectis | Variants de méganucléase clivant une séquence d'adn cible dans le gène was et leurs utilisations |
| EP2633040B1 (fr) | 2010-10-27 | 2019-07-10 | Cellectis | Procédé permettant d'augmenter l'efficacité d'une mutagenèse induite par des cassures double brin |
| WO2012138901A1 (fr) | 2011-04-05 | 2012-10-11 | Cellectis Sa | Procédé pour l'amélioration de l'efficacité d'endonucléases à coupure rare et ses utilisations |
| DK2694091T3 (da) | 2011-04-05 | 2019-06-03 | Cellectis | Fremgangsmåde til fremstilling af kompakte tale-nukleaser og anvendelse heraf |
| WO2012158778A1 (fr) | 2011-05-16 | 2012-11-22 | Cellectis S.A. | Souches d'algues ou de cyanobactéries transgéniques deux fois plus sûres pour empêcher leur implantation et leur dissémination dans des écosystèmes naturels |
| WO2013009525A1 (fr) | 2011-07-08 | 2013-01-17 | Cellectis S.A. | Procédé d'amélioration de l'efficacité de mutagenèse induite par une cassure double brin |
| CN104046593A (zh) * | 2013-03-14 | 2014-09-17 | 浙江大学 | 一种低免疫原性的人细胞及其制备方法 |
| CN115261411A (zh) * | 2013-04-04 | 2022-11-01 | 哈佛学院校长同事会 | 利用CRISPR/Cas系统的基因组编辑的治疗性用途 |
| US10968426B2 (en) | 2015-05-08 | 2021-04-06 | President And Fellows Of Harvard College | Universal donor stem cells and related methods |
| CA3001008A1 (fr) | 2015-10-05 | 2017-04-13 | Precision Biosciences, Inc. | Meganucleases modifiees avec des sequences de reconnaissances rencontrees dans le gene de la region constante alpha du recepteur des lymphocytes t humains |
| AU2016333898B2 (en) | 2015-10-05 | 2020-11-12 | Precision Biosciences, Inc. | Genetically-modified cells comprising a modified human T cell receptor alpha constant region gene |
| AU2016374253B2 (en) * | 2015-12-18 | 2021-10-21 | Sangamo Therapeutics, Inc. | Targeted disruption of the MHC cell receptor |
| CN110869046A (zh) | 2017-03-31 | 2020-03-06 | 塞勒克提斯公司 | 通用型抗cd22嵌合抗原受体工程化的免疫细胞 |
| JP2020529834A (ja) | 2017-06-30 | 2020-10-15 | プレシジョン バイオサイエンシズ，インク． | Ｔ細胞受容体アルファ遺伝子の改変されたイントロンを含む遺伝子改変ｔ細胞 |
| TW201923073A (zh) * | 2017-11-20 | 2019-06-16 | 新加坡商泰莎治療私人有限公司 | 經修飾之k562細胞 |
| MX2020010795A (es) | 2018-04-12 | 2021-01-08 | Prec Biosciences Inc | Nucleasas modificadas genéticamente optimizadas que tienen especificidad para el gen de la región constante alfa del receptor de linfocitos t humanos. |
| WO2020087010A1 (fr) * | 2018-10-25 | 2020-04-30 | Ling Ming | Compositions et procédés pour la sélection dans l'édition de gènes biallélique |
| CA3135799A1 (fr) | 2019-04-03 | 2020-10-08 | Precision Biosciences, Inc. | Cellules immunitaires genetiquement modifiees comprenant un arnsh adapte au microarn (shrnamir) |
| CN114026228A (zh) * | 2019-05-07 | 2022-02-08 | 精密生物科学公司 | 用于识别序列的工程化大范围核酸酶的优化 |
| US11661459B2 (en) | 2020-12-03 | 2023-05-30 | Century Therapeutics, Inc. | Artificial cell death polypeptide for chimeric antigen receptor and uses thereof |
| CN115475247B (zh) * | 2021-06-16 | 2024-02-20 | 厦门大学 | β2-微球蛋白或其抑制剂的制药用途 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004067753A2 (fr) * | 2003-01-28 | 2004-08-12 | Cellectis | Utilisation de meganucleases pour induire une recombinaison homologue ex vivo et in toto dans des tissus somatiques de vertebre et application de cette utilisation |
| WO2006097784A1 (fr) * | 2005-03-15 | 2006-09-21 | Cellectis | Variants de meganuclease i-crei presentant une specificite modifiee, leur procede de preparation, et leurs utilisations |
| AU2006272634B2 (en) * | 2005-07-26 | 2013-01-24 | Sangamo Therapeutics, Inc. | Targeted integration and expression of exogenous nucleic acid sequences |
-
2007
- 2007-02-20 WO PCT/IB2007/001532 patent/WO2008102199A1/fr active Application Filing
-
2008
- 2008-02-20 JP JP2009550342A patent/JP2010518832A/ja active Pending
- 2008-02-20 CN CN200880005471A patent/CN101678126A/zh active Pending
- 2008-02-20 WO PCT/IB2008/001334 patent/WO2008102274A2/fr active Application Filing
- 2008-02-20 EP EP08751044A patent/EP2121036A2/fr not_active Withdrawn
- 2008-02-20 AU AU2008218605A patent/AU2008218605A1/en not_active Abandoned
- 2008-02-20 CA CA002678709A patent/CA2678709A1/fr not_active Abandoned
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2017508468A (ja) * | 2014-03-11 | 2017-03-30 | セレクティスＣｅｌｌｅｃｔｉｓ | 同種移植に適合するｔ細胞を作製するための方法 |
| JP2020114229A (ja) * | 2014-03-11 | 2020-07-30 | セレクティスＣｅｌｌｅｃｔｉｓ | 同種移植に適合するｔ細胞を作製するための方法 |
| JP7105266B2 (ja) | 2014-03-11 | 2022-07-22 | セレクティス | 同種移植に適合するｔ細胞を作製するための方法 |
| JP2022101530A (ja) * | 2015-06-30 | 2022-07-06 | セレクティス | 特異的エンドヌクレアーゼを使用した遺伝子不活化によってｎｋ細胞の機能性を改善する方法 |
| JP7520062B2 (ja) | 2015-06-30 | 2024-07-22 | セレクティス | 特異的エンドヌクレアーゼを使用した遺伝子不活化によってｎｋ細胞の機能性を改善する方法 |
| JP2018538000A (ja) * | 2015-12-23 | 2018-12-27 | プレシジョン バイオサイエンシズ，インク． | ヒトβ−２ミクログロブリン遺伝子に見られる認識配列を有する操作されたメガヌクレアーゼ |
| JP2021101704A (ja) * | 2015-12-23 | 2021-07-15 | プレシジョン バイオサイエンシズ，インク． | ヒトβ−２ミクログロブリン遺伝子に見られる認識配列を有する操作されたメガヌクレアーゼ |
| JP7203873B2 (ja) | 2015-12-23 | 2023-01-13 | プレシジョン バイオサイエンシズ，インク． | ヒトβ－２ミクログロブリン遺伝子に見られる認識配列を有する操作されたメガヌクレアーゼ |
| JP2023052095A (ja) * | 2015-12-23 | 2023-04-11 | プレシジョン バイオサイエンシズ，インク． | ヒトβ－２ミクログロブリン遺伝子に見られる認識配列を有する操作されたメガヌクレアーゼ |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2008102274A3 (fr) | 2009-02-12 |
| CA2678709A1 (fr) | 2008-08-28 |
| WO2008102199A1 (fr) | 2008-08-28 |
| AU2008218605A1 (en) | 2008-08-28 |
| WO2008102274A2 (fr) | 2008-08-28 |
| CN101678126A (zh) | 2010-03-24 |
| EP2121036A2 (fr) | 2009-11-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2010518832A (ja) | ベータ−２−ミクログロブリン遺伝子からのｄｎａ標的配列を切断するメガヌクレアーゼ変異型及びその使用 | |
| EP2167656B1 (fr) | Variants de méganucléase clivant une séquence cible d'adn du locus rosa26 de souris et leurs utilisations | |
| JP5453097B2 (ja) | Ｈｐｒｔ遺伝子からのｄｎａ標的配列を切断するメガヌクレアーゼ変異型及びその使用 | |
| EP1989299B1 (fr) | Variants de méganucléases coupant une séquence d'adn cible d'un gène de xéroderma pigmentosum et leurs utilisations | |
| US9273296B2 (en) | Meganuclease variants cleaving a DNA target sequence from a glutamine synthetase gene and uses thereof | |
| JP2010535472A (ja) | ヒトインターロイキン−２受容体ガンマ鎖遺伝子からのｄｎａ標的配列を切断するメガヌクレアーゼ変異型及びその使用 | |
| JP2009543574A (ja) | Ｒａｇ遺伝子からのｄｎａ標的配列を切断するメガヌクレアーゼ変異型及びその使用 | |
| JP2010534070A (ja) | ヒトヘモグロビンベータ遺伝子からのｄｎａ標的配列を切断するメガヌクレアーゼ変異型及びその使用 | |
| JP2010528649A (ja) | Ｉ−ＣｒｅＩ由来メガヌクレアーゼの切断活性を増強させる方法 | |
| JP2011504744A (ja) | 新規な基質特異性を有するＩ−ＭｓｏＩホーミングエンドヌクレアーゼ変異型及びその使用 |