CA3034882A1 - Regulation of gene expression using engineered nucleases - Google Patents
Regulation of gene expression using engineered nucleases Download PDFInfo
- Publication number
- CA3034882A1 CA3034882A1 CA3034882A CA3034882A CA3034882A1 CA 3034882 A1 CA3034882 A1 CA 3034882A1 CA 3034882 A CA3034882 A CA 3034882A CA 3034882 A CA3034882 A CA 3034882A CA 3034882 A1 CA3034882 A1 CA 3034882A1
- Authority
- CA
- Canada
- Prior art keywords
- cell
- cells
- dna
- sequence
- cleavage
- 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
- 101710163270 Nuclease Proteins 0.000 title description 134
- 230000014493 regulation of gene expression Effects 0.000 title description 2
- 230000004048 modification Effects 0.000 claims abstract description 49
- 238000012986 modification Methods 0.000 claims abstract description 49
- 238000010362 genome editing Methods 0.000 claims abstract description 19
- 210000004027 cell Anatomy 0.000 claims description 377
- 108010017070 Zinc Finger Nucleases Proteins 0.000 claims description 128
- 238000000034 method Methods 0.000 claims description 108
- 230000014509 gene expression Effects 0.000 claims description 94
- 101000903703 Homo sapiens B-cell lymphoma/leukemia 11A Proteins 0.000 claims description 86
- 102100022976 B-cell lymphoma/leukemia 11A Human genes 0.000 claims description 84
- 108060003196 globin Proteins 0.000 claims description 65
- 239000002157 polynucleotide Substances 0.000 claims description 64
- 102000040430 polynucleotide Human genes 0.000 claims description 64
- 108091033319 polynucleotide Proteins 0.000 claims description 64
- 108020004999 messenger RNA Proteins 0.000 claims description 63
- 102000018146 globin Human genes 0.000 claims description 60
- 102100038617 Hemoglobin subunit gamma-2 Human genes 0.000 claims description 37
- 108091005886 Hemoglobin subunit gamma Proteins 0.000 claims description 36
- 108020001507 fusion proteins Proteins 0.000 claims description 26
- 102000037865 fusion proteins Human genes 0.000 claims description 26
- 108700028146 Genetic Enhancer Elements Proteins 0.000 claims description 24
- 210000000130 stem cell Anatomy 0.000 claims description 24
- 238000012217 deletion Methods 0.000 claims description 23
- 230000037430 deletion Effects 0.000 claims description 23
- 238000003780 insertion Methods 0.000 claims description 22
- 230000037431 insertion Effects 0.000 claims description 22
- 108091005904 Hemoglobin subunit beta Proteins 0.000 claims description 20
- 208000007056 sickle cell anemia Diseases 0.000 claims description 20
- 102100021519 Hemoglobin subunit beta Human genes 0.000 claims description 19
- 230000001965 increasing effect Effects 0.000 claims description 17
- 208000034737 hemoglobinopathy Diseases 0.000 claims description 15
- 239000002243 precursor Substances 0.000 claims description 14
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 13
- 208000005980 beta thalassemia Diseases 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 102000004127 Cytokines Human genes 0.000 claims description 5
- 108090000695 Cytokines Proteins 0.000 claims description 5
- 210000005260 human cell Anatomy 0.000 claims description 5
- 230000004936 stimulating effect Effects 0.000 claims description 3
- 210000003958 hematopoietic stem cell Anatomy 0.000 abstract description 15
- 108090000623 proteins and genes Proteins 0.000 description 175
- 238000003776 cleavage reaction Methods 0.000 description 162
- 230000007017 scission Effects 0.000 description 162
- 230000035772 mutation Effects 0.000 description 87
- 108020004414 DNA Proteins 0.000 description 78
- 102000004169 proteins and genes Human genes 0.000 description 76
- 235000018102 proteins Nutrition 0.000 description 75
- 150000007523 nucleic acids Chemical class 0.000 description 71
- 230000027455 binding Effects 0.000 description 69
- 102000039446 nucleic acids Human genes 0.000 description 67
- 108020004707 nucleic acids Proteins 0.000 description 67
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 60
- 239000011701 zinc Substances 0.000 description 60
- 229910052725 zinc Inorganic materials 0.000 description 60
- 230000004568 DNA-binding Effects 0.000 description 59
- 239000013598 vector Substances 0.000 description 59
- 101710185494 Zinc finger protein Proteins 0.000 description 51
- 102100023597 Zinc finger protein 816 Human genes 0.000 description 51
- 239000003623 enhancer Substances 0.000 description 48
- 125000003729 nucleotide group Chemical group 0.000 description 44
- 108090000765 processed proteins & peptides Proteins 0.000 description 43
- 239000002773 nucleotide Substances 0.000 description 41
- 230000010354 integration Effects 0.000 description 36
- 239000000203 mixture Substances 0.000 description 36
- 102000004196 processed proteins & peptides Human genes 0.000 description 36
- 229920001184 polypeptide Polymers 0.000 description 33
- 230000000925 erythroid effect Effects 0.000 description 30
- 108700019146 Transgenes Proteins 0.000 description 28
- 241000699670 Mus sp. Species 0.000 description 27
- 210000003743 erythrocyte Anatomy 0.000 description 27
- 230000004069 differentiation Effects 0.000 description 26
- 230000000694 effects Effects 0.000 description 26
- 238000011282 treatment Methods 0.000 description 26
- 230000003612 virological effect Effects 0.000 description 26
- 210000001185 bone marrow Anatomy 0.000 description 25
- 230000004927 fusion Effects 0.000 description 25
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 24
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 24
- 238000004458 analytical method Methods 0.000 description 24
- 235000001014 amino acid Nutrition 0.000 description 23
- 238000006471 dimerization reaction Methods 0.000 description 21
- 108010077544 Chromatin Proteins 0.000 description 20
- 102000052510 DNA-Binding Proteins Human genes 0.000 description 20
- 229910019142 PO4 Inorganic materials 0.000 description 20
- 150000001413 amino acids Chemical class 0.000 description 20
- 210000003483 chromatin Anatomy 0.000 description 20
- 238000001727 in vivo Methods 0.000 description 20
- 235000021317 phosphate Nutrition 0.000 description 20
- 238000012239 gene modification Methods 0.000 description 19
- 238000000338 in vitro Methods 0.000 description 19
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 18
- 210000004369 blood Anatomy 0.000 description 18
- 239000008280 blood Substances 0.000 description 18
- 230000001413 cellular effect Effects 0.000 description 18
- 108700020911 DNA-Binding Proteins Proteins 0.000 description 17
- 230000006870 function Effects 0.000 description 17
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 17
- 239000010452 phosphate Substances 0.000 description 17
- 239000000047 product Substances 0.000 description 17
- 101001105486 Homo sapiens Proteasome subunit alpha type-7 Proteins 0.000 description 16
- 102100021201 Proteasome subunit alpha type-7 Human genes 0.000 description 16
- 210000001519 tissue Anatomy 0.000 description 16
- 108091034117 Oligonucleotide Proteins 0.000 description 15
- 238000012546 transfer Methods 0.000 description 15
- 239000013603 viral vector Substances 0.000 description 15
- PZNPLUBHRSSFHT-RRHRGVEJSA-N 1-hexadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCCCCCCCCCCCCC PZNPLUBHRSSFHT-RRHRGVEJSA-N 0.000 description 14
- 241001465754 Metazoa Species 0.000 description 14
- 230000005782 double-strand break Effects 0.000 description 14
- 238000001890 transfection Methods 0.000 description 14
- 125000000539 amino acid group Chemical group 0.000 description 13
- 230000001105 regulatory effect Effects 0.000 description 13
- 108091026890 Coding region Proteins 0.000 description 12
- 108010054147 Hemoglobins Proteins 0.000 description 12
- 102000001554 Hemoglobins Human genes 0.000 description 12
- 101100493741 Homo sapiens BCL11A gene Proteins 0.000 description 12
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 12
- 238000013461 design Methods 0.000 description 12
- 238000001415 gene therapy Methods 0.000 description 12
- 238000002347 injection Methods 0.000 description 12
- 239000007924 injection Substances 0.000 description 12
- 239000013612 plasmid Substances 0.000 description 12
- -1 silencers Substances 0.000 description 12
- 108091028043 Nucleic acid sequence Proteins 0.000 description 11
- 208000002903 Thalassemia Diseases 0.000 description 11
- 238000003556 assay Methods 0.000 description 11
- 238000012350 deep sequencing Methods 0.000 description 11
- 230000001404 mediated effect Effects 0.000 description 11
- 102000004190 Enzymes Human genes 0.000 description 10
- 108090000790 Enzymes Proteins 0.000 description 10
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 10
- 241000699666 Mus <mouse, genus> Species 0.000 description 10
- 241000700605 Viruses Species 0.000 description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
- 238000004520 electroporation Methods 0.000 description 10
- 239000012634 fragment Substances 0.000 description 10
- 230000003993 interaction Effects 0.000 description 10
- 210000005259 peripheral blood Anatomy 0.000 description 10
- 239000011886 peripheral blood Substances 0.000 description 10
- 238000002054 transplantation Methods 0.000 description 10
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 9
- 206010068051 Chimerism Diseases 0.000 description 9
- 108010042407 Endonucleases Proteins 0.000 description 9
- 102000004533 Endonucleases Human genes 0.000 description 9
- 238000010459 TALEN Methods 0.000 description 9
- 108010043645 Transcription Activator-Like Effector Nucleases Proteins 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 9
- 201000010099 disease Diseases 0.000 description 9
- 239000003550 marker Substances 0.000 description 9
- 230000007246 mechanism Effects 0.000 description 9
- 239000002953 phosphate buffered saline Substances 0.000 description 9
- 239000000523 sample Substances 0.000 description 9
- 238000006467 substitution reaction Methods 0.000 description 9
- 230000002103 transcriptional effect Effects 0.000 description 9
- 241000701161 unidentified adenovirus Species 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 108700028369 Alleles Proteins 0.000 description 8
- 108091023040 Transcription factor Proteins 0.000 description 8
- 102000040945 Transcription factor Human genes 0.000 description 8
- 235000009697 arginine Nutrition 0.000 description 8
- 210000002798 bone marrow cell Anatomy 0.000 description 8
- 150000002632 lipids Chemical class 0.000 description 8
- 230000006780 non-homologous end joining Effects 0.000 description 8
- 230000009438 off-target cleavage Effects 0.000 description 8
- 239000002245 particle Substances 0.000 description 8
- 230000008569 process Effects 0.000 description 8
- 230000008439 repair process Effects 0.000 description 8
- 108091008146 restriction endonucleases Proteins 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 230000001225 therapeutic effect Effects 0.000 description 8
- 239000004475 Arginine Substances 0.000 description 7
- 102000053602 DNA Human genes 0.000 description 7
- 206010043391 Thalassaemia beta Diseases 0.000 description 7
- 230000004075 alteration Effects 0.000 description 7
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 229940098773 bovine serum albumin Drugs 0.000 description 7
- 230000003197 catalytic effect Effects 0.000 description 7
- 210000000349 chromosome Anatomy 0.000 description 7
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 7
- 230000003394 haemopoietic effect Effects 0.000 description 7
- 238000002744 homologous recombination Methods 0.000 description 7
- 230000006801 homologous recombination Effects 0.000 description 7
- 208000018337 inherited hemoglobinopathy Diseases 0.000 description 7
- 239000002502 liposome Substances 0.000 description 7
- 238000004806 packaging method and process Methods 0.000 description 7
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 7
- 230000001177 retroviral effect Effects 0.000 description 7
- 238000010453 CRISPR/Cas method Methods 0.000 description 6
- 102000014914 Carrier Proteins Human genes 0.000 description 6
- 241000702421 Dependoparvovirus Species 0.000 description 6
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 6
- 208000026350 Inborn Genetic disease Diseases 0.000 description 6
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 6
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 6
- 230000004913 activation Effects 0.000 description 6
- 108091008324 binding proteins Proteins 0.000 description 6
- 230000002950 deficient Effects 0.000 description 6
- 230000001419 dependent effect Effects 0.000 description 6
- 230000034431 double-strand break repair via homologous recombination Effects 0.000 description 6
- 210000000267 erythroid cell Anatomy 0.000 description 6
- 208000016361 genetic disease Diseases 0.000 description 6
- 230000002779 inactivation Effects 0.000 description 6
- 210000004185 liver Anatomy 0.000 description 6
- 230000014759 maintenance of location Effects 0.000 description 6
- 230000010076 replication Effects 0.000 description 6
- 238000012163 sequencing technique Methods 0.000 description 6
- 238000010361 transduction Methods 0.000 description 6
- 230000026683 transduction Effects 0.000 description 6
- 108091093088 Amplicon Proteins 0.000 description 5
- 230000007018 DNA scission Effects 0.000 description 5
- 102000003951 Erythropoietin Human genes 0.000 description 5
- 108090000394 Erythropoietin Proteins 0.000 description 5
- 230000001594 aberrant effect Effects 0.000 description 5
- 238000013459 approach Methods 0.000 description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 229960002685 biotin Drugs 0.000 description 5
- 239000011616 biotin Substances 0.000 description 5
- 230000002759 chromosomal effect Effects 0.000 description 5
- 238000010276 construction Methods 0.000 description 5
- 238000012937 correction Methods 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 238000009510 drug design Methods 0.000 description 5
- 229940105423 erythropoietin Drugs 0.000 description 5
- 230000002068 genetic effect Effects 0.000 description 5
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 5
- 239000000178 monomer Substances 0.000 description 5
- 239000001301 oxygen Substances 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 5
- 230000002265 prevention Effects 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 238000009738 saturating Methods 0.000 description 5
- 230000008685 targeting Effects 0.000 description 5
- 238000013518 transcription Methods 0.000 description 5
- 230000035897 transcription Effects 0.000 description 5
- 230000009261 transgenic effect Effects 0.000 description 5
- 241001430294 unidentified retrovirus Species 0.000 description 5
- 239000003981 vehicle Substances 0.000 description 5
- 210000003462 vein Anatomy 0.000 description 5
- 239000013607 AAV vector Substances 0.000 description 4
- 241000180579 Arca Species 0.000 description 4
- SPFYMRJSYKOXGV-UHFFFAOYSA-N Baytril Chemical compound C1CN(CC)CCN1C(C(=C1)F)=CC2=C1C(=O)C(C(O)=O)=CN2C1CC1 SPFYMRJSYKOXGV-UHFFFAOYSA-N 0.000 description 4
- 108091033409 CRISPR Proteins 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- 108010008532 Deoxyribonuclease I Proteins 0.000 description 4
- 102000007260 Deoxyribonuclease I Human genes 0.000 description 4
- 108010044495 Fetal Hemoglobin Proteins 0.000 description 4
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 4
- 102100027685 Hemoglobin subunit alpha Human genes 0.000 description 4
- 108091005902 Hemoglobin subunit alpha Proteins 0.000 description 4
- 101100220044 Homo sapiens CD34 gene Proteins 0.000 description 4
- 239000007760 Iscove's Modified Dulbecco's Medium Substances 0.000 description 4
- 241000713666 Lentivirus Species 0.000 description 4
- 239000004472 Lysine Substances 0.000 description 4
- 108010077850 Nuclear Localization Signals Proteins 0.000 description 4
- 210000003719 b-lymphocyte Anatomy 0.000 description 4
- 229940105596 baytril Drugs 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 125000002091 cationic group Chemical group 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 230000000875 corresponding effect Effects 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 230000003828 downregulation Effects 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 230000001605 fetal effect Effects 0.000 description 4
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 4
- 238000001802 infusion Methods 0.000 description 4
- 239000012212 insulator Substances 0.000 description 4
- 230000000670 limiting effect Effects 0.000 description 4
- 238000001638 lipofection Methods 0.000 description 4
- 230000007935 neutral effect Effects 0.000 description 4
- 238000005457 optimization Methods 0.000 description 4
- 230000008488 polyadenylation Effects 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 230000006798 recombination Effects 0.000 description 4
- 238000005215 recombination Methods 0.000 description 4
- 238000010561 standard procedure Methods 0.000 description 4
- 238000011144 upstream manufacturing Methods 0.000 description 4
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 3
- 101710096438 DNA-binding protein Proteins 0.000 description 3
- 102100031690 Erythroid transcription factor Human genes 0.000 description 3
- 101710100588 Erythroid transcription factor Proteins 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 108010085682 Hemoglobin A Proteins 0.000 description 3
- 102000007513 Hemoglobin A Human genes 0.000 description 3
- 102100039894 Hemoglobin subunit delta Human genes 0.000 description 3
- 108091005903 Hemoglobin subunit delta Proteins 0.000 description 3
- 102000006947 Histones Human genes 0.000 description 3
- 108010033040 Histones Proteins 0.000 description 3
- 206010020751 Hypersensitivity Diseases 0.000 description 3
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 3
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 3
- 102000011931 Nucleoproteins Human genes 0.000 description 3
- 108010061100 Nucleoproteins Proteins 0.000 description 3
- 108010047956 Nucleosomes Proteins 0.000 description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 3
- 208000018020 Sickle cell-beta-thalassemia disease syndrome Diseases 0.000 description 3
- 201000006288 alpha thalassemia Diseases 0.000 description 3
- 208000007502 anemia Diseases 0.000 description 3
- 230000003115 biocidal effect Effects 0.000 description 3
- 230000033228 biological regulation Effects 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 235000018417 cysteine Nutrition 0.000 description 3
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 3
- 239000000539 dimer Substances 0.000 description 3
- 230000000447 dimerizing effect Effects 0.000 description 3
- 210000001671 embryonic stem cell Anatomy 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 230000007159 enucleation Effects 0.000 description 3
- 230000002538 fungal effect Effects 0.000 description 3
- 102000034356 gene-regulatory proteins Human genes 0.000 description 3
- 108091006104 gene-regulatory proteins Proteins 0.000 description 3
- 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 description 3
- 239000005090 green fluorescent protein Substances 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 210000004263 induced pluripotent stem cell Anatomy 0.000 description 3
- 238000010255 intramuscular injection Methods 0.000 description 3
- 239000007927 intramuscular injection Substances 0.000 description 3
- 238000010253 intravenous injection Methods 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 230000011987 methylation Effects 0.000 description 3
- 238000007069 methylation reaction Methods 0.000 description 3
- 239000002105 nanoparticle Substances 0.000 description 3
- 210000001623 nucleosome Anatomy 0.000 description 3
- 230000009437 off-target effect Effects 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 238000002823 phage display Methods 0.000 description 3
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 3
- YIQPUIGJQJDJOS-UHFFFAOYSA-N plerixafor Chemical compound C=1C=C(CN2CCNCCCNCCNCCC2)C=CC=1CN1CCCNCCNCCCNCC1 YIQPUIGJQJDJOS-UHFFFAOYSA-N 0.000 description 3
- 229960002169 plerixafor Drugs 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 230000000644 propagated effect Effects 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 208000011580 syndromic disease Diseases 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 238000013519 translation Methods 0.000 description 3
- GJTBSTBJLVYKAU-XVFCMESISA-N 2-thiouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=S)NC(=O)C=C1 GJTBSTBJLVYKAU-XVFCMESISA-N 0.000 description 2
- NMUSYJAQQFHJEW-UHFFFAOYSA-N 5-Azacytidine Natural products O=C1N=C(N)N=CN1C1C(O)C(O)C(CO)O1 NMUSYJAQQFHJEW-UHFFFAOYSA-N 0.000 description 2
- NMUSYJAQQFHJEW-KVTDHHQDSA-N 5-azacytidine Chemical compound O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NMUSYJAQQFHJEW-KVTDHHQDSA-N 0.000 description 2
- 108020005544 Antisense RNA Proteins 0.000 description 2
- 102000008682 Argonaute Proteins Human genes 0.000 description 2
- 108010088141 Argonaute Proteins Proteins 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 2
- 102100022548 Beta-hexosaminidase subunit alpha Human genes 0.000 description 2
- 206010010099 Combined immunodeficiency Diseases 0.000 description 2
- 108020004635 Complementary DNA Proteins 0.000 description 2
- 230000004544 DNA amplification Effects 0.000 description 2
- 108010053770 Deoxyribonucleases Proteins 0.000 description 2
- 102000016911 Deoxyribonucleases Human genes 0.000 description 2
- 208000015872 Gaucher disease Diseases 0.000 description 2
- 241000713813 Gibbon ape leukemia virus Species 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 208000031220 Hemophilia Diseases 0.000 description 2
- 208000009292 Hemophilia A Diseases 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 2
- 101000687346 Homo sapiens PR domain zinc finger protein 2 Proteins 0.000 description 2
- 108090000144 Human Proteins Proteins 0.000 description 2
- 102000003839 Human Proteins Human genes 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 2
- 102100034349 Integrase Human genes 0.000 description 2
- 108010061833 Integrases Proteins 0.000 description 2
- 201000001779 Leukocyte adhesion deficiency Diseases 0.000 description 2
- 108091036060 Linker DNA Proteins 0.000 description 2
- 208000036696 Microcytic anaemia Diseases 0.000 description 2
- 208000002678 Mucopolysaccharidoses Diseases 0.000 description 2
- 206010056886 Mucopolysaccharidosis I Diseases 0.000 description 2
- 241000714177 Murine leukemia virus Species 0.000 description 2
- 108091061960 Naked DNA Proteins 0.000 description 2
- 238000012408 PCR amplification Methods 0.000 description 2
- 102100024885 PR domain zinc finger protein 2 Human genes 0.000 description 2
- 241000235648 Pichia Species 0.000 description 2
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 2
- MUPFEKGTMRGPLJ-RMMQSMQOSA-N Raffinose Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O[C@@]2(CO)[C@H](O)[C@@H](O)[C@@H](CO)O2)O1)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 MUPFEKGTMRGPLJ-RMMQSMQOSA-N 0.000 description 2
- 241000235070 Saccharomyces Species 0.000 description 2
- 241000235346 Schizosaccharomyces Species 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- 241000713311 Simian immunodeficiency virus Species 0.000 description 2
- 206010041660 Splenomegaly Diseases 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- 208000022292 Tay-Sachs disease Diseases 0.000 description 2
- 108010073062 Transcription Activator-Like Effectors Proteins 0.000 description 2
- 229940127174 UCHT1 Drugs 0.000 description 2
- MUPFEKGTMRGPLJ-UHFFFAOYSA-N UNPD196149 Natural products OC1C(O)C(CO)OC1(CO)OC1C(O)C(O)C(O)C(COC2C(C(O)C(O)C(CO)O2)O)O1 MUPFEKGTMRGPLJ-UHFFFAOYSA-N 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- 206010068348 X-linked lymphoproliferative syndrome Diseases 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 229960002756 azacitidine Drugs 0.000 description 2
- 210000003445 biliary tract Anatomy 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 238000012754 cardiac puncture Methods 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 210000003763 chloroplast Anatomy 0.000 description 2
- 208000016532 chronic granulomatous disease Diseases 0.000 description 2
- 230000003750 conditioning effect Effects 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000004925 denaturation Methods 0.000 description 2
- 230000036425 denaturation Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 230000005684 electric field Effects 0.000 description 2
- 238000012407 engineering method Methods 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 230000010437 erythropoiesis Effects 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 239000012894 fetal calf serum Substances 0.000 description 2
- 210000003754 fetus Anatomy 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 229930182830 galactose Natural products 0.000 description 2
- 238000001476 gene delivery Methods 0.000 description 2
- 230000005017 genetic modification Effects 0.000 description 2
- 235000013617 genetically modified food Nutrition 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 210000002767 hepatic artery Anatomy 0.000 description 2
- 210000003494 hepatocyte Anatomy 0.000 description 2
- 229960000890 hydrocortisone Drugs 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 229960001330 hydroxycarbamide Drugs 0.000 description 2
- 230000001506 immunosuppresive effect Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 230000002452 interceptive effect Effects 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000004255 ion exchange chromatography Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 210000001161 mammalian embryo Anatomy 0.000 description 2
- 238000007726 management method Methods 0.000 description 2
- 238000013507 mapping Methods 0.000 description 2
- 230000035800 maturation Effects 0.000 description 2
- 210000002901 mesenchymal stem cell Anatomy 0.000 description 2
- 108091070501 miRNA Proteins 0.000 description 2
- 206010028093 mucopolysaccharidosis Diseases 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 230000001400 myeloablative effect Effects 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 210000004940 nucleus Anatomy 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 210000003463 organelle Anatomy 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 230000000737 periodic effect Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 239000013600 plasmid vector Substances 0.000 description 2
- 229960000502 poloxamer Drugs 0.000 description 2
- 229920001983 poloxamer Polymers 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 210000001236 prokaryotic cell Anatomy 0.000 description 2
- 102000021127 protein binding proteins Human genes 0.000 description 2
- 108091011138 protein binding proteins Proteins 0.000 description 2
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 2
- MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 description 2
- 102000037983 regulatory factors Human genes 0.000 description 2
- 108091008025 regulatory factors Proteins 0.000 description 2
- 238000010187 selection method Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 238000010381 tandem affinity purification Methods 0.000 description 2
- 230000002123 temporal effect Effects 0.000 description 2
- 208000035203 thalassemia minor Diseases 0.000 description 2
- 238000010257 thawing Methods 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 239000003053 toxin Substances 0.000 description 2
- 231100000765 toxin Toxicity 0.000 description 2
- 108700012359 toxins Proteins 0.000 description 2
- 108091008023 transcriptional regulators Proteins 0.000 description 2
- 238000010396 two-hybrid screening Methods 0.000 description 2
- 241000701447 unidentified baculovirus Species 0.000 description 2
- 241001529453 unidentified herpesvirus Species 0.000 description 2
- 239000004474 valine Substances 0.000 description 2
- 125000002987 valine group Chemical group [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- BRCNMMGLEUILLG-NTSWFWBYSA-N (4s,5r)-4,5,6-trihydroxyhexan-2-one Chemical group CC(=O)C[C@H](O)[C@H](O)CO BRCNMMGLEUILLG-NTSWFWBYSA-N 0.000 description 1
- VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 description 1
- 125000003974 3-carbamimidamidopropyl group Chemical group C(N)(=N)NCCC* 0.000 description 1
- 125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 description 1
- ZAYHVCMSTBRABG-UHFFFAOYSA-N 5-Methylcytidine Natural products O=C1N=C(N)C(C)=CN1C1C(O)C(O)C(CO)O1 ZAYHVCMSTBRABG-UHFFFAOYSA-N 0.000 description 1
- ZAYHVCMSTBRABG-JXOAFFINSA-N 5-methylcytidine Chemical compound O=C1N=C(N)C(C)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 ZAYHVCMSTBRABG-JXOAFFINSA-N 0.000 description 1
- 230000005730 ADP ribosylation Effects 0.000 description 1
- 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 description 1
- 102100024643 ATP-binding cassette sub-family D member 1 Human genes 0.000 description 1
- 108010013043 Acetylesterase Proteins 0.000 description 1
- 101710159080 Aconitate hydratase A Proteins 0.000 description 1
- 101710159078 Aconitate hydratase B Proteins 0.000 description 1
- 208000029483 Acquired immunodeficiency Diseases 0.000 description 1
- 201000010028 Acrocephalosyndactylia Diseases 0.000 description 1
- 241001655883 Adeno-associated virus - 1 Species 0.000 description 1
- 241000702423 Adeno-associated virus - 2 Species 0.000 description 1
- 241000202702 Adeno-associated virus - 3 Species 0.000 description 1
- 241000580270 Adeno-associated virus - 4 Species 0.000 description 1
- 241001634120 Adeno-associated virus - 5 Species 0.000 description 1
- 241000972680 Adeno-associated virus - 6 Species 0.000 description 1
- 241001164823 Adeno-associated virus - 7 Species 0.000 description 1
- 241001164825 Adeno-associated virus - 8 Species 0.000 description 1
- 208000002485 Adiposis dolorosa Diseases 0.000 description 1
- 201000011452 Adrenoleukodystrophy Diseases 0.000 description 1
- 208000024341 Aicardi syndrome Diseases 0.000 description 1
- 206010056292 Androgen-Insensitivity Syndrome Diseases 0.000 description 1
- 208000025490 Apert syndrome Diseases 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 1
- 201000005943 Barth syndrome Diseases 0.000 description 1
- 208000015885 Blue rubber bleb nevus Diseases 0.000 description 1
- 206010070918 Bone deformity Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 101000981881 Brevibacillus parabrevis ATP-dependent glycine adenylase Proteins 0.000 description 1
- 101000981889 Brevibacillus parabrevis Linear gramicidin-PCP reductase Proteins 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
- 208000022526 Canavan disease Diseases 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 108090000565 Capsid Proteins Proteins 0.000 description 1
- 108090000994 Catalytic RNA Proteins 0.000 description 1
- 102000053642 Catalytic RNA Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 206010008723 Chondrodystrophy Diseases 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 208000006992 Color Vision Defects Diseases 0.000 description 1
- 206010053138 Congenital aplastic anaemia Diseases 0.000 description 1
- 206010011385 Cri-du-chat syndrome Diseases 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- 230000033616 DNA repair Effects 0.000 description 1
- 241000450599 DNA viruses Species 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 101100278839 Drosophila melanogaster sw gene Proteins 0.000 description 1
- 206010058314 Dysplasia Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 101800001467 Envelope glycoprotein E2 Proteins 0.000 description 1
- 101710091045 Envelope protein Proteins 0.000 description 1
- 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 description 1
- 108060002716 Exonuclease Proteins 0.000 description 1
- 208000024720 Fabry Disease Diseases 0.000 description 1
- 108010076282 Factor IX Proteins 0.000 description 1
- 201000004939 Fanconi anemia Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 241000724791 Filamentous phage Species 0.000 description 1
- 208000001914 Fragile X syndrome Diseases 0.000 description 1
- 201000011240 Frontotemporal dementia Diseases 0.000 description 1
- 102000048120 Galactokinases Human genes 0.000 description 1
- 108700023157 Galactokinases Proteins 0.000 description 1
- 208000009796 Gangliosidoses Diseases 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- 208000034951 Genetic Translocation Diseases 0.000 description 1
- 208000010055 Globoid Cell Leukodystrophy Diseases 0.000 description 1
- 206010053185 Glycogen storage disease type II Diseases 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 1
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 1
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 1
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical group NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 1
- 108020005004 Guide RNA Proteins 0.000 description 1
- 206010018910 Haemolysis Diseases 0.000 description 1
- 208000018565 Hemochromatosis Diseases 0.000 description 1
- 108010085686 Hemoglobin C Proteins 0.000 description 1
- 102100038614 Hemoglobin subunit gamma-1 Human genes 0.000 description 1
- 208000002972 Hepatolenticular Degeneration Diseases 0.000 description 1
- 108091027305 Heteroduplex Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 description 1
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 1
- 101000851181 Homo sapiens Epidermal growth factor receptor Proteins 0.000 description 1
- 101000932480 Homo sapiens Fms-related tyrosine kinase 3 ligand Proteins 0.000 description 1
- 101001031977 Homo sapiens Hemoglobin subunit gamma-1 Proteins 0.000 description 1
- 101001031961 Homo sapiens Hemoglobin subunit gamma-2 Proteins 0.000 description 1
- 101000976075 Homo sapiens Insulin Proteins 0.000 description 1
- 101000716729 Homo sapiens Kit ligand Proteins 0.000 description 1
- 101001046587 Homo sapiens Krueppel-like factor 1 Proteins 0.000 description 1
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 1
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 1
- 101000615488 Homo sapiens Methyl-CpG-binding domain protein 2 Proteins 0.000 description 1
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 1
- 101000581981 Homo sapiens Neural cell adhesion molecule 1 Proteins 0.000 description 1
- 101001109800 Homo sapiens Pro-neuregulin-1, membrane-bound isoform Proteins 0.000 description 1
- 101001000998 Homo sapiens Protein phosphatase 1 regulatory subunit 12C Proteins 0.000 description 1
- 101000799461 Homo sapiens Thrombopoietin Proteins 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 208000015178 Hurler syndrome Diseases 0.000 description 1
- 208000025500 Hutchinson-Gilford progeria syndrome Diseases 0.000 description 1
- 206010049933 Hypophosphatasia Diseases 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 1
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 208000028547 Inborn Urea Cycle disease Diseases 0.000 description 1
- 102000012330 Integrases Human genes 0.000 description 1
- 108010002386 Interleukin-3 Proteins 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- 206010065973 Iron Overload Diseases 0.000 description 1
- 241000581650 Ivesia Species 0.000 description 1
- 208000028226 Krabbe disease Diseases 0.000 description 1
- 102100022248 Krueppel-like factor 1 Human genes 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- 206010050638 Langer-Giedion syndrome Diseases 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 102000006830 Luminescent Proteins Human genes 0.000 description 1
- 108010047357 Luminescent Proteins Proteins 0.000 description 1
- 102000008072 Lymphokines Human genes 0.000 description 1
- 108010074338 Lymphokines Proteins 0.000 description 1
- 208000030289 Lymphoproliferative disease Diseases 0.000 description 1
- 208000015439 Lysosomal storage disease Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 208000000916 Mandibulofacial dysostosis Diseases 0.000 description 1
- 208000001826 Marfan syndrome Diseases 0.000 description 1
- 108010049137 Member 1 Subfamily D ATP Binding Cassette Transporter Proteins 0.000 description 1
- 108010063312 Metalloproteins Proteins 0.000 description 1
- 102000010750 Metalloproteins Human genes 0.000 description 1
- 102100021299 Methyl-CpG-binding domain protein 2 Human genes 0.000 description 1
- 108060004795 Methyltransferase Proteins 0.000 description 1
- 108700011259 MicroRNAs Proteins 0.000 description 1
- 108010059724 Micrococcal Nuclease Proteins 0.000 description 1
- 201000002983 Mobius syndrome Diseases 0.000 description 1
- 208000034167 Moebius syndrome Diseases 0.000 description 1
- 241000713869 Moloney murine leukemia virus Species 0.000 description 1
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 1
- 208000001804 Monosomy 5p Diseases 0.000 description 1
- 108010086093 Mung Bean Nuclease Proteins 0.000 description 1
- 125000000729 N-terminal amino-acid group Chemical group 0.000 description 1
- 208000000175 Nail-Patella Syndrome Diseases 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 108700019961 Neoplasm Genes Proteins 0.000 description 1
- 102000048850 Neoplasm Genes Human genes 0.000 description 1
- 102100027347 Neural cell adhesion molecule 1 Human genes 0.000 description 1
- 208000009905 Neurofibromatoses Diseases 0.000 description 1
- 108010008964 Non-Histone Chromosomal Proteins Proteins 0.000 description 1
- 102000006570 Non-Histone Chromosomal Proteins Human genes 0.000 description 1
- 108091007494 Nucleic acid- binding domains Proteins 0.000 description 1
- 108091005461 Nucleic proteins Proteins 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 206010031243 Osteogenesis imperfecta Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- 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 description 1
- 108700019535 Phosphoprotein Phosphatases Proteins 0.000 description 1
- 102000045595 Phosphoprotein Phosphatases Human genes 0.000 description 1
- 208000000609 Pick Disease of the Brain Diseases 0.000 description 1
- 208000024571 Pick disease Diseases 0.000 description 1
- 241000139306 Platt Species 0.000 description 1
- 241000097929 Porphyria Species 0.000 description 1
- 208000010642 Porphyrias Diseases 0.000 description 1
- 201000010769 Prader-Willi syndrome Diseases 0.000 description 1
- 208000007932 Progeria Diseases 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 108700040121 Protein Methyltransferases Proteins 0.000 description 1
- 102000055027 Protein Methyltransferases Human genes 0.000 description 1
- 101710188315 Protein X Proteins 0.000 description 1
- 102100035620 Protein phosphatase 1 regulatory subunit 12C Human genes 0.000 description 1
- 208000007531 Proteus syndrome Diseases 0.000 description 1
- 241000125945 Protoparvovirus Species 0.000 description 1
- 102000044126 RNA-Binding Proteins Human genes 0.000 description 1
- 230000004570 RNA-binding Effects 0.000 description 1
- 101710105008 RNA-binding protein Proteins 0.000 description 1
- 108091030071 RNAI Proteins 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 238000010240 RT-PCR analysis Methods 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 102000018120 Recombinases Human genes 0.000 description 1
- 108010091086 Recombinases Proteins 0.000 description 1
- 108700005075 Regulator Genes Proteins 0.000 description 1
- 108091081062 Repeated sequence (DNA) Proteins 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 201000000582 Retinoblastoma Diseases 0.000 description 1
- 208000006289 Rett Syndrome Diseases 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 206010039281 Rubinstein-Taybi syndrome Diseases 0.000 description 1
- 101001025539 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) Homothallic switching endonuclease Proteins 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 201000004283 Shwachman-Diamond syndrome Diseases 0.000 description 1
- 108010016797 Sickle Hemoglobin Proteins 0.000 description 1
- 206010040642 Sickle cell anaemia with crisis Diseases 0.000 description 1
- 208000000859 Sickle cell trait Diseases 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- 108091027967 Small hairpin RNA Proteins 0.000 description 1
- 201000001388 Smith-Magenis syndrome Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 208000027077 Stickler syndrome Diseases 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 101800001271 Surface protein Proteins 0.000 description 1
- 241000589499 Thermus thermophilus Species 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 1
- 108010022394 Threonine synthase Proteins 0.000 description 1
- 102000036693 Thrombopoietin Human genes 0.000 description 1
- 108010041111 Thrombopoietin Proteins 0.000 description 1
- 101710183280 Topoisomerase Proteins 0.000 description 1
- 108091028113 Trans-activating crRNA Proteins 0.000 description 1
- 108700009124 Transcription Initiation Site Proteins 0.000 description 1
- 102000004338 Transferrin Human genes 0.000 description 1
- 108090000901 Transferrin Proteins 0.000 description 1
- 201000003199 Treacher Collins syndrome Diseases 0.000 description 1
- 208000035378 Trichorhinophalangeal syndrome type 2 Diseases 0.000 description 1
- 208000037280 Trisomy Diseases 0.000 description 1
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
- 208000026911 Tuberous sclerosis complex Diseases 0.000 description 1
- 208000026928 Turner syndrome Diseases 0.000 description 1
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical group O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- 206010046865 Vaccinia virus infection Diseases 0.000 description 1
- 108020005202 Viral DNA Proteins 0.000 description 1
- 108700005077 Viral Genes Proteins 0.000 description 1
- 208000026724 Waardenburg syndrome Diseases 0.000 description 1
- 206010049644 Williams syndrome Diseases 0.000 description 1
- 208000018839 Wilson disease Diseases 0.000 description 1
- 208000006110 Wiskott-Aldrich syndrome Diseases 0.000 description 1
- 208000022440 X-linked sideroblastic anemia 1 Diseases 0.000 description 1
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 208000008919 achondroplasia Diseases 0.000 description 1
- 201000000761 achromatopsia Diseases 0.000 description 1
- DPKHZNPWBDQZCN-UHFFFAOYSA-N acridine orange free base Chemical compound C1=CC(N(C)C)=CC2=NC3=CC(N(C)C)=CC=C3C=C21 DPKHZNPWBDQZCN-UHFFFAOYSA-N 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 201000009628 adenosine deaminase deficiency Diseases 0.000 description 1
- 230000004931 aggregating effect Effects 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 208000006682 alpha 1-Antitrypsin Deficiency Diseases 0.000 description 1
- 108010069455 alpha(A) globin Proteins 0.000 description 1
- 229960000723 ampicillin Drugs 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
- 210000004102 animal cell Anatomy 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 230000001745 anti-biotin effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 238000002617 apheresis Methods 0.000 description 1
- 150000001483 arginine derivatives Chemical class 0.000 description 1
- 150000001484 arginines Chemical class 0.000 description 1
- 230000003126 arrythmogenic effect Effects 0.000 description 1
- 210000004436 artificial bacterial chromosome Anatomy 0.000 description 1
- 210000001106 artificial yeast chromosome Anatomy 0.000 description 1
- 208000036556 autosomal recessive T cell-negative B cell-negative NK cell-negative due to adenosine deaminase deficiency severe combined immunodeficiency Diseases 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- DZBUGLKDJFMEHC-UHFFFAOYSA-N benzoquinolinylidene Natural products C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 229930189065 blasticidin Natural products 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 210000000234 capsid Anatomy 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000007910 cell fusion Effects 0.000 description 1
- 238000011072 cell harvest Methods 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 108091092356 cellular DNA Proteins 0.000 description 1
- 230000009920 chelation Effects 0.000 description 1
- 230000007073 chemical hydrolysis Effects 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000000749 co-immunoprecipitation Methods 0.000 description 1
- 238000000975 co-precipitation Methods 0.000 description 1
- 238000002288 cocrystallisation Methods 0.000 description 1
- 201000007254 color blindness Diseases 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 239000003184 complementary RNA Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 239000005546 dideoxynucleotide Substances 0.000 description 1
- 102000004419 dihydrofolate reductase Human genes 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 241001493065 dsRNA viruses Species 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 208000002169 ectodermal dysplasia Diseases 0.000 description 1
- 208000031068 ectodermal dysplasia syndrome Diseases 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 210000002308 embryonic cell Anatomy 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 108010048367 enhanced green fluorescent protein Proteins 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 230000007071 enzymatic hydrolysis Effects 0.000 description 1
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
- 230000001973 epigenetic effect Effects 0.000 description 1
- 210000003013 erythroid precursor cell Anatomy 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 102000013165 exonuclease Human genes 0.000 description 1
- 230000001036 exonucleolytic effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 108700014844 flt3 ligand Proteins 0.000 description 1
- 108091006047 fluorescent proteins Proteins 0.000 description 1
- 102000034287 fluorescent proteins Human genes 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 238000003197 gene knockdown Methods 0.000 description 1
- 230000030279 gene silencing Effects 0.000 description 1
- 230000009368 gene silencing by RNA Effects 0.000 description 1
- 238000012226 gene silencing method Methods 0.000 description 1
- 230000009395 genetic defect Effects 0.000 description 1
- 230000007614 genetic variation Effects 0.000 description 1
- 238000012268 genome sequencing Methods 0.000 description 1
- 238000003205 genotyping method Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 229960002743 glutamine Drugs 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 201000004502 glycogen storage disease II Diseases 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 208000035474 group of disease Diseases 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 150000003278 haem Chemical group 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 230000008588 hemolysis Effects 0.000 description 1
- 230000002949 hemolytic effect Effects 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- ZFGMDIBRIDKWMY-PASTXAENSA-N heparin Chemical compound CC(O)=N[C@@H]1[C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O[C@@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O[C@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@@H](O[C@@H]3[C@@H](OC(O)[C@H](OS(O)(=O)=O)[C@H]3O)C(O)=O)O[C@@H]2O)CS(O)(=O)=O)[C@H](O)[C@H]1O ZFGMDIBRIDKWMY-PASTXAENSA-N 0.000 description 1
- 229960001008 heparin sodium Drugs 0.000 description 1
- 208000020451 hereditary persistence of fetal hemoglobin Diseases 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000012165 high-throughput sequencing Methods 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 102000052096 human BCL11A Human genes 0.000 description 1
- 102000055151 human KITLG Human genes 0.000 description 1
- 102000055650 human NRG1 Human genes 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 208000006278 hypochromic anemia Diseases 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 229960000318 kanamycin Drugs 0.000 description 1
- 229930027917 kanamycin Natural products 0.000 description 1
- 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 1
- 229930182823 kanamycin A Natural products 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 208000036546 leukodystrophy Diseases 0.000 description 1
- 208000004731 long QT syndrome Diseases 0.000 description 1
- 210000005265 lung cell Anatomy 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 239000002679 microRNA Substances 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 208000024191 minimally invasive lung adenocarcinoma Diseases 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000009126 molecular therapy Methods 0.000 description 1
- 208000005340 mucopolysaccharidosis III Diseases 0.000 description 1
- 208000011045 mucopolysaccharidosis type 3 Diseases 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 230000002988 nephrogenic effect Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 238000007857 nested PCR Methods 0.000 description 1
- 201000004931 neurofibromatosis Diseases 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 210000003924 normoblast Anatomy 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 230000032696 parturition Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 210000003049 pelvic bone Anatomy 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000008298 phosphoramidates Chemical class 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 102000054765 polymorphisms of proteins Human genes 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 210000003240 portal vein Anatomy 0.000 description 1
- 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 238000003133 propidium iodide exclusion Methods 0.000 description 1
- 230000004224 protection Effects 0.000 description 1
- 230000004853 protein function Effects 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 229950010131 puromycin Drugs 0.000 description 1
- 238000003762 quantitative reverse transcription PCR Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 108010054624 red fluorescent protein Proteins 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 238000010008 shearing Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 235000021391 short chain fatty acids Nutrition 0.000 description 1
- 150000004666 short chain fatty acids Chemical class 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 238000010911 splenectomy Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000012134 supernatant fraction Substances 0.000 description 1
- 230000000153 supplemental effect Effects 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 208000037369 susceptibility to malaria Diseases 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical group [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 210000002303 tibia Anatomy 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 238000000954 titration curve Methods 0.000 description 1
- 230000037426 transcriptional repression Effects 0.000 description 1
- 230000002463 transducing effect Effects 0.000 description 1
- 239000012581 transferrin Substances 0.000 description 1
- 238000012301 transgenic model Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000010474 transient expression Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 201000006532 trichorhinophalangeal syndrome type II Diseases 0.000 description 1
- RYYVLZVUVIJVGH-UHFFFAOYSA-N trimethylxanthine Natural products CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 1
- 238000009966 trimming Methods 0.000 description 1
- 230000010415 tropism Effects 0.000 description 1
- 208000009999 tuberous sclerosis Diseases 0.000 description 1
- 238000003160 two-hybrid assay Methods 0.000 description 1
- 230000034512 ubiquitination Effects 0.000 description 1
- 238000010798 ubiquitination Methods 0.000 description 1
- 210000003954 umbilical cord Anatomy 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 208000030954 urea cycle disease Diseases 0.000 description 1
- 208000007089 vaccinia Diseases 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 239000000277 virosome Substances 0.000 description 1
- 230000036266 weeks of gestation Effects 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- 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 [RNase]; Deoxyribonucleases [DNase]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/28—Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- C—CHEMISTRY; METALLURGY
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
- C12N15/90—Stable introduction of foreign DNA into chromosome
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
- C12N15/90—Stable introduction of foreign DNA into chromosome
- C12N15/902—Stable introduction of foreign DNA into chromosome using homologous recombination
- C12N15/907—Stable introduction of foreign DNA into chromosome using homologous recombination in mammalian cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K2035/124—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells the cells being hematopoietic, bone marrow derived or blood cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/09—Fusion polypeptide containing a localisation/targetting motif containing a nuclear localisation signal
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/80—Fusion polypeptide containing a DNA binding domain, e.g. Lacl or Tet-repressor
- C07K2319/81—Fusion polypeptide containing a DNA binding domain, e.g. Lacl or Tet-repressor containing a Zn-finger domain for DNA binding
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Medicinal Chemistry (AREA)
- Plant Pathology (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Cell Biology (AREA)
- Hematology (AREA)
- Immunology (AREA)
- Developmental Biology & Embryology (AREA)
- Mycology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Virology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Enzymes And Modification Thereof (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662378978P | 2016-08-24 | 2016-08-24 | |
| US62/378,978 | 2016-08-24 | ||
| US201762443981P | 2017-01-09 | 2017-01-09 | |
| US62/443,981 | 2017-01-09 | ||
| US201762545778P | 2017-08-15 | 2017-08-15 | |
| US62/545,778 | 2017-08-15 | ||
| PCT/US2017/048397 WO2018039440A1 (en) | 2016-08-24 | 2017-08-24 | Regulation of gene expression using engineered nucleases |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3034882A1 true CA3034882A1 (en) | 2018-03-01 |
Family
ID=61246246
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3034882A Pending CA3034882A1 (en) | 2016-08-24 | 2017-08-24 | Regulation of gene expression using engineered nucleases |
Country Status (32)
Families Citing this family (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2853829C (en) | 2011-07-22 | 2023-09-26 | President And Fellows Of Harvard College | Evaluation and improvement of nuclease cleavage specificity |
| US9163284B2 (en) | 2013-08-09 | 2015-10-20 | President And Fellows Of Harvard College | Methods for identifying a target site of a Cas9 nuclease |
| US9359599B2 (en) | 2013-08-22 | 2016-06-07 | President And Fellows Of Harvard College | Engineered transcription activator-like effector (TALE) domains and uses thereof |
| US9388430B2 (en) | 2013-09-06 | 2016-07-12 | President And Fellows Of Harvard College | Cas9-recombinase fusion proteins and uses thereof |
| US9526784B2 (en) | 2013-09-06 | 2016-12-27 | President And Fellows Of Harvard College | Delivery system for functional nucleases |
| US9228207B2 (en) | 2013-09-06 | 2016-01-05 | President And Fellows Of Harvard College | Switchable gRNAs comprising aptamers |
| US20150166982A1 (en) | 2013-12-12 | 2015-06-18 | President And Fellows Of Harvard College | Methods for correcting pi3k point mutations |
| EP3177718B1 (en) | 2014-07-30 | 2022-03-16 | President and Fellows of Harvard College | Cas9 proteins including ligand-dependent inteins |
| SG11201803173VA (en) | 2015-10-23 | 2018-05-30 | Harvard College | Nucleobase editors and uses thereof |
| JP7231935B2 (ja) | 2016-08-03 | 2023-03-08 | プレジデント アンド フェローズ オブ ハーバード カレッジ | アデノシン核酸塩基編集因子およびそれらの使用 |
| CA3033327A1 (en) | 2016-08-09 | 2018-02-15 | President And Fellows Of Harvard College | Programmable cas9-recombinase fusion proteins and uses thereof |
| CA3034882A1 (en) * | 2016-08-24 | 2018-03-01 | Sangamo Therapeutics, Inc. | Regulation of gene expression using engineered nucleases |
| WO2018039438A1 (en) | 2016-08-24 | 2018-03-01 | President And Fellows Of Harvard College | Incorporation of unnatural amino acids into proteins using base editing |
| BR112019003327A2 (pt) | 2016-08-24 | 2019-07-02 | Sangamo Therapeutics, Inc. | nucleases manipuladas de alvo específico |
| WO2018071868A1 (en) | 2016-10-14 | 2018-04-19 | President And Fellows Of Harvard College | Aav delivery of nucleobase editors |
| KR102674612B1 (ko) * | 2016-12-01 | 2024-06-14 | 상가모 테라퓨틱스, 인코포레이티드 | Tau 조절제 및 그것의 전달을 위한 방법 및 조성물 |
| US10745677B2 (en) | 2016-12-23 | 2020-08-18 | President And Fellows Of Harvard College | Editing of CCR5 receptor gene to protect against HIV infection |
| TW201839136A (zh) | 2017-02-06 | 2018-11-01 | 瑞士商諾華公司 | 治療血色素異常症之組合物及方法 |
| US12390514B2 (en) | 2017-03-09 | 2025-08-19 | President And Fellows Of Harvard College | Cancer vaccine |
| EP3592853A1 (en) | 2017-03-09 | 2020-01-15 | President and Fellows of Harvard College | Suppression of pain by gene editing |
| JP2020510439A (ja) | 2017-03-10 | 2020-04-09 | プレジデント アンド フェローズ オブ ハーバード カレッジ | シトシンからグアニンへの塩基編集因子 |
| KR20240116572A (ko) | 2017-03-23 | 2024-07-29 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | 핵산 프로그램가능한 dna 결합 단백질을 포함하는 핵염기 편집제 |
| US11560566B2 (en) | 2017-05-12 | 2023-01-24 | President And Fellows Of Harvard College | Aptazyme-embedded guide RNAs for use with CRISPR-Cas9 in genome editing and transcriptional activation |
| EP3658573A1 (en) | 2017-07-28 | 2020-06-03 | President and Fellows of Harvard College | Methods and compositions for evolving base editors using phage-assisted continuous evolution (pace) |
| WO2019139645A2 (en) | 2017-08-30 | 2019-07-18 | President And Fellows Of Harvard College | High efficiency base editors comprising gam |
| AU2018352592C1 (en) | 2017-10-16 | 2025-09-25 | Beam Therapeutics, Inc. | Uses of adenosine base editors |
| JP2021502085A (ja) * | 2017-11-09 | 2021-01-28 | サンガモ セラピューティクス， インコーポレイテッド | サイトカイン誘導性ｓｈ２含有タンパク質（ｃｉｓｈ）遺伝子の遺伝子改変 |
| EP3724214A4 (en) | 2017-12-15 | 2021-09-01 | The Broad Institute Inc. | SYSTEMS AND METHODS FOR PREDICTING REPAIR RESULTS IN GENETIC ENGINEERING |
| CA3089587A1 (en) | 2018-02-08 | 2019-08-15 | Sangamo Therapeutics, Inc. | Engineered target specific nucleases |
| US12157760B2 (en) | 2018-05-23 | 2024-12-03 | The Broad Institute, Inc. | Base editors and uses thereof |
| WO2020072677A1 (en) | 2018-10-02 | 2020-04-09 | Sangamo Therapeutics, Inc. | Methods and compositions for modulation of tau proteins |
| US12281338B2 (en) | 2018-10-29 | 2025-04-22 | The Broad Institute, Inc. | Nucleobase editors comprising GeoCas9 and uses thereof |
| US12351837B2 (en) | 2019-01-23 | 2025-07-08 | The Broad Institute, Inc. | Supernegatively charged proteins and uses thereof |
| GB2601617B (en) | 2019-03-19 | 2024-02-21 | Broad Inst Inc | Methods and compositions for editing nucleotide sequences |
| JP2022519949A (ja) | 2019-04-02 | 2022-03-25 | サンガモ セラピューティクス， インコーポレイテッド | ベータ－サラセミアの治療のための方法 |
| US12473543B2 (en) | 2019-04-17 | 2025-11-18 | The Broad Institute, Inc. | Adenine base editors with reduced off-target effects |
| US12435330B2 (en) | 2019-10-10 | 2025-10-07 | The Broad Institute, Inc. | Methods and compositions for prime editing RNA |
| DE112021002672T5 (de) | 2020-05-08 | 2023-04-13 | President And Fellows Of Harvard College | Vefahren und zusammensetzungen zum gleichzeitigen editieren beider stränge einer doppelsträngigen nukleotid-zielsequenz |
| CN114149990A (zh) * | 2020-09-08 | 2022-03-08 | 甘李药业股份有限公司 | 编辑造血干/祖细胞中bcl11a基因的方法 |
| US11514747B2 (en) | 2020-09-30 | 2022-11-29 | Aristocrat Technologies, Inc. | Latching assembly for a pushbutton of an electronic gaming machine |
| WO2023014839A1 (en) * | 2021-08-03 | 2023-02-09 | Sangamo Therapeutics, Inc. | Methods for the treatment of sickle cell disease |
| WO2025128871A2 (en) | 2023-12-13 | 2025-06-19 | Renagade Therapeutics Management Inc. | Lipid nanoparticles comprising coding rna molecules for use in gene editing and as vaccines and therapeutic agents |
| WO2025174765A1 (en) | 2024-02-12 | 2025-08-21 | Renagade Therapeutics Management Inc. | Lipid nanoparticles comprising coding rna molecules for use in gene editing and as vaccines and therapeutic agents |
Family Cites Families (123)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4217344A (en) | 1976-06-23 | 1980-08-12 | L'oreal | Compositions containing aqueous dispersions of lipid spheres |
| US4235871A (en) | 1978-02-24 | 1980-11-25 | Papahadjopoulos Demetrios P | Method of encapsulating biologically active materials in lipid vesicles |
| US4186183A (en) | 1978-03-29 | 1980-01-29 | The United States Of America As Represented By The Secretary Of The Army | Liposome carriers in chemotherapy of leishmaniasis |
| US4261975A (en) | 1979-09-19 | 1981-04-14 | Merck & Co., Inc. | Viral liposome particle |
| US4485054A (en) | 1982-10-04 | 1984-11-27 | Lipoderm Pharmaceuticals Limited | Method of encapsulating biologically active materials in multilamellar lipid vesicles (MLV) |
| US4501728A (en) | 1983-01-06 | 1985-02-26 | Technology Unlimited, Inc. | Masking of liposomes from RES recognition |
| US4897355A (en) | 1985-01-07 | 1990-01-30 | Syntex (U.S.A.) Inc. | N[ω,(ω-1)-dialkyloxy]- and N-[ω,(ω-1)-dialkenyloxy]-alk-1-yl-N,N,N-tetrasubstituted ammonium lipids and uses therefor |
| US5049386A (en) | 1985-01-07 | 1991-09-17 | Syntex (U.S.A.) Inc. | N-ω,(ω-1)-dialkyloxy)- and N-(ω,(ω-1)-dialkenyloxy)Alk-1-YL-N,N,N-tetrasubstituted ammonium lipids and uses therefor |
| US4946787A (en) | 1985-01-07 | 1990-08-07 | Syntex (U.S.A.) Inc. | N-(ω,(ω-1)-dialkyloxy)- and N-(ω,(ω-1)-dialkenyloxy)-alk-1-yl-N,N,N-tetrasubstituted ammonium lipids and uses therefor |
| US4797368A (en) | 1985-03-15 | 1989-01-10 | The United States Of America As Represented By The Department Of Health And Human Services | Adeno-associated virus as eukaryotic expression vector |
| US4774085A (en) | 1985-07-09 | 1988-09-27 | 501 Board of Regents, Univ. of Texas | Pharmaceutical administration systems containing a mixture of immunomodulators |
| US5422251A (en) | 1986-11-26 | 1995-06-06 | Princeton University | Triple-stranded nucleic acids |
| US4837028A (en) | 1986-12-24 | 1989-06-06 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
| US5176996A (en) | 1988-12-20 | 1993-01-05 | Baylor College Of Medicine | Method for making synthetic oligonucleotides which bind specifically to target sites on duplex DNA molecules, by forming a colinear triplex, the synthetic oligonucleotides and methods of use |
| US5264618A (en) | 1990-04-19 | 1993-11-23 | Vical, Inc. | Cationic lipids for intracellular delivery of biologically active molecules |
| WO1991017424A1 (en) | 1990-05-03 | 1991-11-14 | Vical, Inc. | Intracellular delivery of biologically active substances by means of self-assembling lipid complexes |
| US5173414A (en) | 1990-10-30 | 1992-12-22 | Applied Immune Sciences, Inc. | Production of recombinant adeno-associated virus vectors |
| US5356802A (en) | 1992-04-03 | 1994-10-18 | The Johns Hopkins University | Functional domains in flavobacterium okeanokoites (FokI) restriction endonuclease |
| US5436150A (en) | 1992-04-03 | 1995-07-25 | The Johns Hopkins University | Functional domains in flavobacterium okeanokoities (foki) restriction endonuclease |
| US5487994A (en) | 1992-04-03 | 1996-01-30 | The Johns Hopkins University | Insertion and deletion mutants of FokI restriction endonuclease |
| US5587308A (en) | 1992-06-02 | 1996-12-24 | The United States Of America As Represented By The Department Of Health & Human Services | Modified adeno-associated virus vector capable of expression from a novel promoter |
| US6140466A (en) | 1994-01-18 | 2000-10-31 | The Scripps Research Institute | Zinc finger protein derivatives and methods therefor |
| US6242568B1 (en) | 1994-01-18 | 2001-06-05 | The Scripps Research Institute | Zinc finger protein derivatives and methods therefor |
| AU704601B2 (en) | 1994-01-18 | 1999-04-29 | Scripps Research Institute, The | Zinc finger protein derivatives and methods therefor |
| AU696455C (en) | 1994-03-23 | 2006-03-02 | Case Western Reserve University | Compacted nucleic acids and their delivery to cells |
| USRE39229E1 (en) | 1994-08-20 | 2006-08-08 | Gendaq Limited | Binding proteins for recognition of DNA |
| GB9824544D0 (en) | 1998-11-09 | 1999-01-06 | Medical Res Council | Screening system |
| US5789538A (en) | 1995-02-03 | 1998-08-04 | Massachusetts Institute Of Technology | Zinc finger proteins with high affinity new DNA binding specificities |
| US5925523A (en) | 1996-08-23 | 1999-07-20 | President & Fellows Of Harvard College | Intraction trap assay, reagents and uses thereof |
| GB2338237B (en) | 1997-02-18 | 2001-02-28 | Actinova Ltd | In vitro peptide or protein expression library |
| GB9703369D0 (en) | 1997-02-18 | 1997-04-09 | Lindqvist Bjorn H | Process |
| GB9710807D0 (en) | 1997-05-23 | 1997-07-23 | Medical Res Council | Nucleic acid binding proteins |
| GB9710809D0 (en) | 1997-05-23 | 1997-07-23 | Medical Res Council | Nucleic acid binding proteins |
| US6989264B2 (en) | 1997-09-05 | 2006-01-24 | Targeted Genetics Corporation | Methods for generating high titer helper-free preparations of released recombinant AAV vectors |
| US6410248B1 (en) | 1998-01-30 | 2002-06-25 | Massachusetts Institute Of Technology | General strategy for selecting high-affinity zinc finger proteins for diverse DNA target sites |
| US6479626B1 (en) | 1998-03-02 | 2002-11-12 | Massachusetts Institute Of Technology | Poly zinc finger proteins with improved linkers |
| US6140081A (en) | 1998-10-16 | 2000-10-31 | The Scripps Research Institute | Zinc finger binding domains for GNN |
| US6534261B1 (en) | 1999-01-12 | 2003-03-18 | Sangamo Biosciences, Inc. | Regulation of endogenous gene expression in cells using zinc finger proteins |
| US6599692B1 (en) | 1999-09-14 | 2003-07-29 | Sangamo Bioscience, Inc. | Functional genomics using zinc finger proteins |
| US7013219B2 (en) | 1999-01-12 | 2006-03-14 | Sangamo Biosciences, Inc. | Regulation of endogenous gene expression in cells using zinc finger proteins |
| US6453242B1 (en) | 1999-01-12 | 2002-09-17 | Sangamo Biosciences, Inc. | Selection of sites for targeting by zinc finger proteins and methods of designing zinc finger proteins to bind to preselected sites |
| US7070934B2 (en) | 1999-01-12 | 2006-07-04 | Sangamo Biosciences, Inc. | Ligand-controlled regulation of endogenous gene expression |
| US6794136B1 (en) | 2000-11-20 | 2004-09-21 | Sangamo Biosciences, Inc. | Iterative optimization in the design of binding proteins |
| US7030215B2 (en) | 1999-03-24 | 2006-04-18 | Sangamo Biosciences, Inc. | Position dependent recognition of GNN nucleotide triplets by zinc fingers |
| EP1236045B1 (en) | 1999-12-06 | 2005-11-09 | Sangamo Biosciences Inc. | Methods of using randomized libraries of zinc finger proteins for the identification of gene function |
| CA2398590C (en) | 2000-02-08 | 2012-08-28 | Sangamo Biosciences, Inc. | Cells for drug discovery |
| US20020061512A1 (en) | 2000-02-18 | 2002-05-23 | Kim Jin-Soo | Zinc finger domains and methods of identifying same |
| WO2001088197A2 (en) | 2000-05-16 | 2001-11-22 | Massachusetts Institute Of Technology | Methods and compositions for interaction trap assays |
| JP2002060786A (ja) | 2000-08-23 | 2002-02-26 | Kao Corp | 硬質表面用殺菌防汚剤 |
| US7067317B2 (en) | 2000-12-07 | 2006-06-27 | Sangamo Biosciences, Inc. | Regulation of angiogenesis with zinc finger proteins |
| US20050267061A1 (en) | 2004-04-08 | 2005-12-01 | Sangamo Biosciences, Inc. | Methods and compositions for treating neuropathic and neurodegenerative conditions |
| EP1353941B1 (en) | 2001-01-22 | 2013-03-13 | Sangamo BioSciences, Inc. | Modified zinc finger binding proteins |
| GB0108491D0 (en) | 2001-04-04 | 2001-05-23 | Gendaq Ltd | Engineering zinc fingers |
| WO2003016496A2 (en) | 2001-08-20 | 2003-02-27 | The Scripps Research Institute | Zinc finger binding domains for cnn |
| US6723551B2 (en) | 2001-11-09 | 2004-04-20 | The United States Of America As Represented By The Department Of Health And Human Services | Production of adeno-associated virus in insect cells |
| WO2003042361A2 (en) | 2001-11-09 | 2003-05-22 | Government Of The United States Of America, Department Of Health And Human Services | Production of adeno-associated virus in insect cells |
| US7262054B2 (en) | 2002-01-22 | 2007-08-28 | Sangamo Biosciences, Inc. | Zinc finger proteins for DNA binding and gene regulation in plants |
| JP4968498B2 (ja) | 2002-01-23 | 2012-07-04 | ユニバーシティ オブ ユタ リサーチ ファウンデーション | ジンクフィンガーヌクレアーゼを用いる、標的化された染色体変異誘発 |
| EP2368982A3 (en) | 2002-03-21 | 2011-10-12 | Sangamo BioSciences, Inc. | Methods and compositions for using zinc finger endonucleases to enhance homologous recombination |
| US7074596B2 (en) | 2002-03-25 | 2006-07-11 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Synthesis and use of anti-reverse mRNA cap analogues |
| US7419817B2 (en) | 2002-05-17 | 2008-09-02 | The United States Of America As Represented By The Secretary Department Of Health And Human Services, Nih. | Scalable purification of AAV2, AAV4 or AAV5 using ion-exchange chromatography |
| US7361635B2 (en) | 2002-08-29 | 2008-04-22 | Sangamo Biosciences, Inc. | Simultaneous modulation of multiple genes |
| US9447434B2 (en) | 2002-09-05 | 2016-09-20 | California Institute Of Technology | Use of chimeric nucleases to stimulate gene targeting |
| US7888121B2 (en) | 2003-08-08 | 2011-02-15 | Sangamo Biosciences, Inc. | Methods and compositions for targeted cleavage and recombination |
| US8409861B2 (en) | 2003-08-08 | 2013-04-02 | Sangamo Biosciences, Inc. | Targeted deletion of cellular DNA sequences |
| US7972854B2 (en) | 2004-02-05 | 2011-07-05 | Sangamo Biosciences, Inc. | Methods and compositions for targeted cleavage and recombination |
| CA2562193A1 (en) | 2004-04-08 | 2005-10-27 | Sangamo Biosciences, Inc. | Treatment of neuropathic pain with zinc finger proteins |
| CA2579677A1 (en) | 2004-09-16 | 2006-03-30 | Sangamo Biosciences, Inc. | Compositions and methods for protein production |
| MX2007013757A (es) | 2005-05-05 | 2008-01-24 | Univ Arizona | Reagrupacion permitida de secuencia (seer)-met odo de novedad para visualizar secuencias de adn especificas. |
| ATE462783T1 (de) | 2006-05-25 | 2010-04-15 | Sangamo Biosciences Inc | Variante foki-spaltungshälften-domänen |
| EP2765195A1 (en) | 2006-05-25 | 2014-08-13 | Sangamo BioSciences, Inc. | Methods and compositions for gene inactivation |
| EP2049663B1 (en) | 2006-08-11 | 2015-02-25 | Dow AgroSciences LLC | Zinc finger nuclease-mediated homologous recombination |
| DE602008003684D1 (de) | 2007-04-26 | 2011-01-05 | Sangamo Biosciences Inc | Gezielte integration in die ppp1r12c-position |
| US8585526B2 (en) | 2007-06-18 | 2013-11-19 | American Axle & Manufacturing, Inc. | Vehicle driveline component having heat sink for increased heat rejection capabilities |
| WO2008157688A2 (en) | 2007-06-19 | 2008-12-24 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Synthesis and use of anti-reverse phosphorothioate analogs of the messenger rna cap |
| US9506120B2 (en) | 2007-09-27 | 2016-11-29 | Sangamo Biosciences, Inc. | Rapid in vivo identification of biologically active nucleases |
| AU2008317354B2 (en) | 2007-10-25 | 2014-04-10 | Ospedale San Raffaele S.R.L. | Methods and compositions for targeted integration |
| DE102007056956B4 (de) | 2007-11-27 | 2009-10-29 | Moosbauer, Peter, Dipl.-Ing.(FH) | Schaltung zur Regelung der Stromversorgung eines Verbrauchers und Verfahren zum Betrieb einer Schaltung |
| EP2281050B1 (en) | 2008-04-14 | 2014-04-02 | Sangamo BioSciences, Inc. | Linear donor constructs for targeted integration |
| CA2725773C (en) | 2008-05-28 | 2017-12-05 | Sangamo Biosciences, Inc. | Compositions for linking dna-binding domains and cleavage domains |
| CA2734235C (en) | 2008-08-22 | 2019-03-26 | Sangamo Biosciences, Inc. | Methods and compositions for targeted single-stranded cleavage and targeted integration |
| EP2334794B8 (en) | 2008-09-15 | 2017-04-19 | The Children's Medical Center Corporation | Modulation of bcl11a for treatment of hemoglobinopathies |
| WO2010065123A1 (en) | 2008-12-04 | 2010-06-10 | Sangamo Biosciences, Inc. | Genome editing in rats using zinc-finger nucleases |
| EP3165234B1 (de) | 2009-07-31 | 2019-04-03 | ethris GmbH | Rna mit einer kombination aus unmodifizierten und modifizierten nucleotiden zur proteinexpression |
| US8956828B2 (en) | 2009-11-10 | 2015-02-17 | Sangamo Biosciences, Inc. | Targeted disruption of T cell receptor genes using engineered zinc finger protein nucleases |
| JP2013511979A (ja) | 2009-11-27 | 2013-04-11 | ビーエーエスエフ プラント サイエンス カンパニー ゲーエムベーハー | キメラエンドヌクレアーゼおよびその使用 |
| CN102947453A (zh) | 2010-01-28 | 2013-02-27 | 费城儿童医院 | 用于病毒载体纯化的可扩缩生产平台和用于基因治疗中的如此纯化的病毒载体 |
| EP2615106B1 (en) | 2010-02-08 | 2018-04-25 | Sangamo Therapeutics, Inc. | Engineered cleavage half-domains |
| AU2011215557B2 (en) | 2010-02-09 | 2016-03-10 | Sangamo Therapeutics, Inc. | Targeted genomic modification with partially single-stranded donor molecules |
| WO2011130624A2 (en) * | 2010-04-16 | 2011-10-20 | Immune Disease Institute, Inc. | Sustained polypeptide expression from synthetic, modified rnas and uses thereof |
| WO2011139336A1 (en) | 2010-04-26 | 2011-11-10 | Sangamo Biosciences, Inc. | Genome editing of a rosa locus using nucleases |
| KR101974036B1 (ko) | 2010-05-03 | 2019-04-30 | 상가모 테라퓨틱스, 인코포레이티드 | 아연 핑거 모듈을 연결하기 위한 조성물 |
| EP2571512B1 (en) | 2010-05-17 | 2017-08-23 | Sangamo BioSciences, Inc. | Novel dna-binding proteins and uses thereof |
| US8945868B2 (en) | 2010-07-21 | 2015-02-03 | Sangamo Biosciences, Inc. | Methods and compositions for modification of a HLA locus |
| US9057057B2 (en) | 2010-07-27 | 2015-06-16 | The Johns Hopkins University | Obligate heterodimer variants of foki cleavage domain |
| GB201014169D0 (en) * | 2010-08-25 | 2010-10-06 | Cambridge Entpr Ltd | In vitro hepatic differentiation |
| US9405700B2 (en) | 2010-11-04 | 2016-08-02 | Sonics, Inc. | Methods and apparatus for virtualization in an integrated circuit |
| CN102358902B (zh) | 2011-04-02 | 2013-01-02 | 西南大学 | 家蚕丝素重链基因突变序列及突变的方法和应用 |
| IL293650B2 (en) | 2011-09-21 | 2024-10-01 | Sangamo Therapeutics Inc | Methods and compositions for regulation of transgene expression |
| AU2012328682B2 (en) | 2011-10-27 | 2017-09-21 | Sangamo Therapeutics, Inc. | Methods and compositions for modification of the HPRT locus |
| WO2013074999A1 (en) | 2011-11-16 | 2013-05-23 | Sangamo Biosciences, Inc. | Modified dna-binding proteins and uses thereof |
| CN103361328B (zh) * | 2012-03-30 | 2017-08-18 | 复旦大学 | 介导整合的hiv‑1前病毒基因敲除的锌指核酸内切酶及其制法和应用 |
| US10174331B2 (en) | 2012-05-07 | 2019-01-08 | Sangamo Therapeutics, Inc. | Methods and compositions for nuclease-mediated targeted integration of transgenes |
| EP2855666B1 (en) | 2012-05-25 | 2019-12-04 | Cellectis | Use of pre t alpha or functional variant thereof for expanding tcr alpha deficient t cells |
| SG11201500852WA (en) * | 2012-08-29 | 2015-04-29 | Sangamo Biosciences Inc | Methods and compositions for treatment of a genetic condition |
| EP2929017A4 (en) | 2012-12-05 | 2016-09-28 | Sangamo Biosciences Inc | METHOD AND COMPOSITIONS FOR REGULATING METABOLISM DISEASES |
| JP6392245B2 (ja) * | 2012-12-18 | 2018-09-19 | ノバルティス アーゲー | 遺伝子改変哺乳動物細胞における治療用タンパク質の産生 |
| KR102874079B1 (ko) | 2013-03-15 | 2025-10-22 | 더 제너럴 하스피탈 코포레이션 | Rna-안내 게놈 편집을 위해 특이성을 증가시키기 위한 절단된 안내 rna(tru-grnas)의 이용 |
| WO2014186585A2 (en) * | 2013-05-15 | 2014-11-20 | Sangamo Biosciences, Inc. | Methods and compositions for treatment of a genetic condition |
| CA2920899C (en) | 2013-08-28 | 2023-02-28 | Sangamo Biosciences, Inc. | Compositions for linking dna-binding domains and cleavage domains |
| WO2015073683A2 (en) | 2013-11-13 | 2015-05-21 | Children's Medical Center Corporation | Nuclease-mediated regulation of gene expression |
| DK3080274T3 (da) | 2013-12-09 | 2020-08-31 | Sangamo Therapeutics Inc | Fremgangsmåder og sammensætninger til genom-manipulation |
| US20170037431A1 (en) * | 2014-05-01 | 2017-02-09 | University Of Washington | In vivo Gene Engineering with Adenoviral Vectors |
| BR112016025849A2 (pt) | 2014-05-08 | 2017-10-17 | Chdi Foundation Inc | métodos e composições para o tratamento da doença de huntington |
| WO2016014794A1 (en) * | 2014-07-25 | 2016-01-28 | Sangamo Biosciences, Inc. | Methods and compositions for modulating nuclease-mediated genome engineering in hematopoietic stem cells |
| EP3054007A1 (en) | 2015-02-09 | 2016-08-10 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Recombinant adeno-associated virus particle purification comprising an immuno-affinity purification step |
| MX382223B (es) * | 2015-05-12 | 2025-03-13 | Sangamo Therapeutics Inc | Regulacion de expresion genica mediada por nucleasa. |
| US9957501B2 (en) * | 2015-06-18 | 2018-05-01 | Sangamo Therapeutics, Inc. | Nuclease-mediated regulation of gene expression |
| CA2991301A1 (en) | 2015-07-13 | 2017-01-19 | Sangamo Therapeutics, Inc. | Delivery methods and compositions for nuclease-mediated genome engineering |
| CA3034882A1 (en) | 2016-08-24 | 2018-03-01 | Sangamo Therapeutics, Inc. | Regulation of gene expression using engineered nucleases |
| BR112019003327A2 (pt) | 2016-08-24 | 2019-07-02 | Sangamo Therapeutics, Inc. | nucleases manipuladas de alvo específico |
| WO2018107026A1 (en) | 2016-12-09 | 2018-06-14 | Sangamo Therapeutics, Inc. | Delivery of target specific nucleases |
| BR112020002438A2 (pt) | 2017-08-08 | 2020-07-28 | Sangamo Therapeutics, Inc. | direcionamento celular mediado por receptores de antígenos quiméricos |
-
2017
- 2017-08-24 CA CA3034882A patent/CA3034882A1/en active Pending
- 2017-08-24 MY MYPI2019000673A patent/MY193234A/en unknown
- 2017-08-24 TN TNP/2019/000048A patent/TN2019000048A1/en unknown
- 2017-08-24 BR BR112019003100-6A patent/BR112019003100A2/pt not_active IP Right Cessation
- 2017-08-24 HU HUE17844404A patent/HUE056707T2/hu unknown
- 2017-08-24 HR HRP20212025TT patent/HRP20212025T1/hr unknown
- 2017-08-24 CN CN201780050637.3A patent/CN110325635B/zh active Active
- 2017-08-24 CR CR20190098A patent/CR20190098A/es unknown
- 2017-08-24 SG SG10201913315SA patent/SG10201913315SA/en unknown
- 2017-08-24 DK DK17844404.8T patent/DK3504229T3/da active
- 2017-08-24 WO PCT/US2017/048397 patent/WO2018039440A1/en not_active Ceased
- 2017-08-24 RS RS20211591A patent/RS62758B1/sr unknown
- 2017-08-24 IL IL264639A patent/IL264639B2/en unknown
- 2017-08-24 EP EP21198842.3A patent/EP3995574A1/en not_active Withdrawn
- 2017-08-24 JP JP2019510787A patent/JP7203014B2/ja active Active
- 2017-08-24 KR KR1020197005015A patent/KR102572759B1/ko active Active
- 2017-08-24 PE PE2019000410A patent/PE20190568A1/es unknown
- 2017-08-24 LT LTEPPCT/US2017/048397T patent/LT3504229T/lt unknown
- 2017-08-24 ES ES17844404T patent/ES2900317T3/es active Active
- 2017-08-24 EP EP17844404.8A patent/EP3504229B1/en active Active
- 2017-08-24 PL PL17844404T patent/PL3504229T3/pl unknown
- 2017-08-24 AU AU2017315406A patent/AU2017315406B2/en active Active
- 2017-08-24 NZ NZ750938A patent/NZ750938A/en unknown
- 2017-08-24 SG SG11201901531TA patent/SG11201901531TA/en unknown
- 2017-08-24 MX MX2019002207A patent/MX2019002207A/es unknown
- 2017-08-24 PT PT178444048T patent/PT3504229T/pt unknown
- 2017-08-24 SI SI201731029T patent/SI3504229T1/sl unknown
-
2019
- 2019-02-06 ZA ZA2019/00765A patent/ZA201900765B/en unknown
- 2019-02-08 PH PH12019500281A patent/PH12019500281A1/en unknown
- 2019-02-14 CL CL2019000399A patent/CL2019000399A1/es unknown
- 2019-02-14 DO DO2019000031A patent/DOP2019000031A/es unknown
- 2019-02-15 CO CONC2019/0001364A patent/CO2019001364A2/es unknown
- 2019-02-21 US US16/281,751 patent/US10563184B2/en active Active
- 2019-03-12 EC ECSENADI201917082A patent/ECSP19017082A/es unknown
-
2020
- 2020-01-09 US US16/738,766 patent/US11845965B2/en active Active
-
2021
- 2021-06-29 AU AU2021204432A patent/AU2021204432B2/en active Active
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2021204432B2 (en) | Regulation of gene expression using engineered nucleases | |
| JP7365374B2 (ja) | ヌクレアーゼ介在性遺伝子発現調節 | |
| EP3068881B1 (en) | Nuclease-mediated regulation of gene expression | |
| US9957501B2 (en) | Nuclease-mediated regulation of gene expression | |
| EP3102673B1 (en) | Methods and compositions for treatment of a beta thalessemia | |
| TWI758316B (zh) | 使用經工程改造之核酸酶調控基因表現 | |
| HK40074078A (en) | Regulation of gene expression using engineered nucleases | |
| HK40008885B (en) | Regulation of gene expression using engineered nucleases | |
| OA19369A (en) | Regulation of gene expression using engineered nucleases. | |
| NZ791706A (en) | Regulation of gene expression using engineered nucleases | |
| EA045868B1 (ru) | Регулирование экспрессии генов с использованием сконструированных нуклеаз |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20211220 |
|
| EEER | Examination request |
Effective date: 20211220 |
|
| EEER | Examination request |
Effective date: 20211220 |
|
| EEER | Examination request |
Effective date: 20211220 |
|
| EEER | Examination request |
Effective date: 20211220 |
|
| EEER | Examination request |
Effective date: 20211220 |