KR20240004276A - 아데노신 데아미나아제 변이체 및 이의 용도 - Google Patents
아데노신 데아미나아제 변이체 및 이의 용도 Download PDFInfo
- Publication number
- KR20240004276A KR20240004276A KR1020237033780A KR20237033780A KR20240004276A KR 20240004276 A KR20240004276 A KR 20240004276A KR 1020237033780 A KR1020237033780 A KR 1020237033780A KR 20237033780 A KR20237033780 A KR 20237033780A KR 20240004276 A KR20240004276 A KR 20240004276A
- Authority
- KR
- South Korea
- Prior art keywords
- adenosine deaminase
- variant
- amino acid
- base editor
- editing
- 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
- 102000055025 Adenosine deaminases Human genes 0.000 title claims abstract description 251
- 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 title claims abstract description 248
- 102000040430 polynucleotide Human genes 0.000 claims abstract description 136
- 108091033319 polynucleotide Proteins 0.000 claims abstract description 136
- 239000002157 polynucleotide Substances 0.000 claims abstract description 136
- 230000000694 effects Effects 0.000 claims abstract description 131
- 229930024421 Adenine Natural products 0.000 claims abstract description 39
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 claims abstract description 39
- 229960000643 adenine Drugs 0.000 claims abstract description 39
- 108020001507 fusion proteins Proteins 0.000 claims abstract description 34
- 102000037865 fusion proteins Human genes 0.000 claims abstract description 34
- 102200033353 rs104893953 Human genes 0.000 claims description 1312
- 102220581619 Iron-sulfur cluster co-chaperone protein HscB_I49K_mutation Human genes 0.000 claims description 1238
- 102200005751 rs1554654024 Human genes 0.000 claims description 756
- 102220222910 rs771332058 Human genes 0.000 claims description 449
- 102220627584 Coagulation factor IX_V30I_mutation Human genes 0.000 claims description 342
- 102200115279 rs121918091 Human genes 0.000 claims description 286
- 102220137031 rs3738985 Human genes 0.000 claims description 174
- 102220498084 Lipoma-preferred partner_Y76L_mutation Human genes 0.000 claims description 172
- 102220377863 c.230A>G Human genes 0.000 claims description 145
- 102220098911 rs878854588 Human genes 0.000 claims description 121
- 102220543795 39S ribosomal protein L15, mitochondrial_P29L_mutation Human genes 0.000 claims description 116
- 102220279102 rs1554656403 Human genes 0.000 claims description 107
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 101
- 102220599875 Unconventional myosin-Vb_A143E_mutation Human genes 0.000 claims description 99
- 238000000034 method Methods 0.000 claims description 91
- 210000004027 cell Anatomy 0.000 claims description 65
- 102220622871 Hemoglobin subunit delta_V30L_mutation Human genes 0.000 claims description 64
- 102220599989 Zinc finger CCCH domain-containing protein 3_F149Y_mutation Human genes 0.000 claims description 64
- 102220548949 Translin-associated factor X-interacting protein 1_F84A_mutation Human genes 0.000 claims description 61
- 102220119836 rs186739900 Human genes 0.000 claims description 61
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 claims description 56
- 108010031325 Cytidine deaminase Proteins 0.000 claims description 53
- 102100026846 Cytidine deaminase Human genes 0.000 claims description 51
- 230000008859 change Effects 0.000 claims description 50
- 108090000623 proteins and genes Proteins 0.000 claims description 42
- 230000004075 alteration Effects 0.000 claims description 37
- 102000004169 proteins and genes Human genes 0.000 claims description 34
- 102220585456 Jouberin_I49N_mutation Human genes 0.000 claims description 31
- 239000013598 vector Substances 0.000 claims description 30
- 102000053602 DNA Human genes 0.000 claims description 29
- 108020004414 DNA Proteins 0.000 claims description 29
- 125000003729 nucleotide group Chemical group 0.000 claims description 28
- 239000002773 nucleotide Substances 0.000 claims description 27
- 239000002126 C01EB10 - Adenosine Substances 0.000 claims description 25
- 108091033409 CRISPR Proteins 0.000 claims description 25
- 229960005305 adenosine Drugs 0.000 claims description 25
- 229920002477 rna polymer Polymers 0.000 claims description 25
- 150000001413 amino acids Chemical class 0.000 claims description 23
- 102220279092 rs200738474 Human genes 0.000 claims description 21
- 102220172111 rs774141923 Human genes 0.000 claims description 21
- 230000004568 DNA-binding Effects 0.000 claims description 18
- 108020005004 Guide RNA Proteins 0.000 claims description 17
- 208000026350 Inborn Genetic disease Diseases 0.000 claims description 17
- 208000016361 genetic disease Diseases 0.000 claims description 17
- 230000001965 increasing effect Effects 0.000 claims description 17
- UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 claims description 16
- UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 claims description 16
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 16
- 102220027754 rs17217772 Human genes 0.000 claims description 16
- 102200082936 rs33950507 Human genes 0.000 claims description 16
- 102200029295 rs5742973 Human genes 0.000 claims description 16
- 102200057511 rs587779858 Human genes 0.000 claims description 16
- 102200164336 rs63750206 Human genes 0.000 claims description 16
- 239000012634 fragment Substances 0.000 claims description 15
- 102220201278 rs767831585 Human genes 0.000 claims description 15
- 238000006481 deamination reaction Methods 0.000 claims description 14
- 102000052510 DNA-Binding Proteins Human genes 0.000 claims description 13
- 230000001105 regulatory effect Effects 0.000 claims description 13
- 230000009615 deamination Effects 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 12
- 102220641874 Granule associated Rac and RHOG effector protein 1_S2H_mutation Human genes 0.000 claims description 11
- 102220470439 Melanoregulin_H96N_mutation Human genes 0.000 claims description 11
- 102200006401 rs199907548 Human genes 0.000 claims description 11
- 102220263142 rs529265811 Human genes 0.000 claims description 11
- 102220062667 rs779791579 Human genes 0.000 claims description 11
- 102220221744 rs894664317 Human genes 0.000 claims description 11
- 101710096438 DNA-binding protein Proteins 0.000 claims description 9
- 230000004048 modification Effects 0.000 claims description 9
- 238000012986 modification Methods 0.000 claims description 9
- 102220576479 Matrix metalloproteinase-9_N127K_mutation Human genes 0.000 claims description 8
- 101710163270 Nuclease Proteins 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 229940035893 uracil Drugs 0.000 claims description 8
- 230000000295 complement effect Effects 0.000 claims description 7
- 241000282414 Homo sapiens Species 0.000 claims description 6
- 101100166144 Staphylococcus aureus cas9 gene Proteins 0.000 claims description 6
- 241000124008 Mammalia Species 0.000 claims description 5
- 125000000539 amino acid group Chemical group 0.000 claims description 5
- 230000001580 bacterial effect Effects 0.000 claims description 5
- 102200016928 c.100G>A Human genes 0.000 claims description 5
- 102220129617 rs140406512 Human genes 0.000 claims description 5
- 102200029323 rs142329098 Human genes 0.000 claims description 5
- 102200024060 rs2606921 Human genes 0.000 claims description 5
- 102220010996 rs730880471 Human genes 0.000 claims description 5
- 102220148703 rs772742922 Human genes 0.000 claims description 5
- 108700004991 Cas12a Proteins 0.000 claims description 4
- 210000004899 c-terminal region Anatomy 0.000 claims description 4
- 238000000338 in vitro Methods 0.000 claims description 4
- 238000001727 in vivo Methods 0.000 claims description 4
- 239000013603 viral vector Substances 0.000 claims description 4
- 108010008532 Deoxyribonuclease I Proteins 0.000 claims description 3
- 102000007260 Deoxyribonuclease I Human genes 0.000 claims description 3
- 108010077850 Nuclear Localization Signals Proteins 0.000 claims description 3
- 241000193996 Streptococcus pyogenes Species 0.000 claims description 3
- 238000011282 treatment Methods 0.000 claims description 3
- 102220629272 Alcohol dehydrogenase 6_P48H_mutation Human genes 0.000 claims description 2
- 102220523641 C-C motif chemokine 2_R47F_mutation Human genes 0.000 claims description 2
- 101000648826 Datura stramonium Tropinone reductase homolog Proteins 0.000 claims description 2
- 241000702421 Dependoparvovirus Species 0.000 claims description 2
- 229940113491 Glycosylase inhibitor Drugs 0.000 claims description 2
- 241000238631 Hexapoda Species 0.000 claims description 2
- 102220474346 L-xylulose reductase_R107A_mutation Human genes 0.000 claims description 2
- 241000711408 Murine respirovirus Species 0.000 claims description 2
- 208000009869 Neu-Laxova syndrome Diseases 0.000 claims description 2
- 102220470512 Proteasome subunit beta type-3_V82G_mutation Human genes 0.000 claims description 2
- 102220554681 Putative uncharacterized protein ZNF252P-AS1_L84I_mutation Human genes 0.000 claims description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims description 2
- 241000194020 Streptococcus thermophilus Species 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 239000013604 expression vector Substances 0.000 claims description 2
- 230000002538 fungal effect Effects 0.000 claims description 2
- 210000005260 human cell Anatomy 0.000 claims description 2
- 210000004962 mammalian cell Anatomy 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 230000001177 retroviral effect Effects 0.000 claims description 2
- 102220320468 rs185031797 Human genes 0.000 claims description 2
- 102200012780 rs372685632 Human genes 0.000 claims description 2
- 102220273513 rs373435521 Human genes 0.000 claims description 2
- 102220095227 rs763804037 Human genes 0.000 claims description 2
- 102220062649 rs786204195 Human genes 0.000 claims description 2
- 102220089709 rs869320709 Human genes 0.000 claims description 2
- 241001529453 unidentified herpesvirus Species 0.000 claims description 2
- UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 claims 3
- 102220218334 rs138729094 Human genes 0.000 claims 3
- 102220125566 rs774511117 Human genes 0.000 claims 3
- 101000910035 Streptococcus pyogenes serotype M1 CRISPR-associated endonuclease Cas9/Csn1 Proteins 0.000 claims 2
- 102220473257 Crossover junction endonuclease EME1_I49V_mutation Human genes 0.000 claims 1
- 102220473607 Cytochrome b5_P48A_mutation Human genes 0.000 claims 1
- 102220350016 c.143C>T Human genes 0.000 claims 1
- 230000004927 fusion Effects 0.000 claims 1
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 abstract description 51
- 229940104302 cytosine Drugs 0.000 abstract description 24
- 108010080611 Cytosine Deaminase Proteins 0.000 abstract description 22
- 102000000311 Cytosine Deaminase Human genes 0.000 abstract description 22
- 108010052875 Adenine deaminase Proteins 0.000 abstract description 7
- 235000001014 amino acid Nutrition 0.000 description 60
- 150000007523 nucleic acids Chemical group 0.000 description 45
- 102000039446 nucleic acids Human genes 0.000 description 39
- 108020004707 nucleic acids Proteins 0.000 description 39
- 235000018102 proteins Nutrition 0.000 description 31
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 30
- 102000004196 processed proteins & peptides Human genes 0.000 description 30
- 108090000765 processed proteins & peptides Proteins 0.000 description 30
- 229920001184 polypeptide Polymers 0.000 description 29
- 229940024606 amino acid Drugs 0.000 description 22
- 201000010099 disease Diseases 0.000 description 19
- UHDGCWIWMRVCDJ-XVFCMESISA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-XVFCMESISA-N 0.000 description 15
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 14
- 208000035475 disorder Diseases 0.000 description 12
- 230000027455 binding Effects 0.000 description 11
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 10
- 230000035772 mutation Effects 0.000 description 10
- 239000002777 nucleoside Substances 0.000 description 10
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 8
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 8
- 229940113082 thymine Drugs 0.000 description 7
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound 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 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 229940088598 enzyme Drugs 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 6
- 239000001257 hydrogen Substances 0.000 description 6
- 230000003993 interaction Effects 0.000 description 6
- -1 small molecule chemical compound Chemical class 0.000 description 6
- 235000000346 sugar Nutrition 0.000 description 6
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 5
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 150000003833 nucleoside derivatives Chemical class 0.000 description 5
- 125000003835 nucleoside group Chemical group 0.000 description 5
- 102220253566 rs761381438 Human genes 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical compound CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 description 4
- 108700040115 Adenosine deaminases Proteins 0.000 description 4
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 4
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 4
- 108700020911 DNA-Binding Proteins Proteins 0.000 description 4
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 4
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 4
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 4
- 229930010555 Inosine Natural products 0.000 description 4
- 108020004511 Recombinant DNA Proteins 0.000 description 4
- 230000009977 dual effect Effects 0.000 description 4
- 230000014509 gene expression Effects 0.000 description 4
- 229960003786 inosine Drugs 0.000 description 4
- 230000001717 pathogenic effect Effects 0.000 description 4
- 238000012216 screening Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- ZDTFMPXQUSBYRL-UUOKFMHZSA-N 2-Aminoadenosine Chemical compound C12=NC(N)=NC(N)=C2N=CN1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O ZDTFMPXQUSBYRL-UUOKFMHZSA-N 0.000 description 3
- 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 3
- 108020004705 Codon Proteins 0.000 description 3
- 102220605874 Cytosolic arginine sensor for mTORC1 subunit 2_D10A_mutation Human genes 0.000 description 3
- 108091028043 Nucleic acid sequence Proteins 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 3
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 239000012636 effector Substances 0.000 description 3
- 230000003301 hydrolyzing effect Effects 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- 230000030648 nucleus localization Effects 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000008439 repair process Effects 0.000 description 3
- 102200062498 rs786204855 Human genes 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 229940104230 thymidine Drugs 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 3
- 229940045145 uridine Drugs 0.000 description 3
- 229940075420 xanthine Drugs 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- YKBGVTZYEHREMT-KVQBGUIXSA-N 2'-deoxyguanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 YKBGVTZYEHREMT-KVQBGUIXSA-N 0.000 description 2
- CKTSBUTUHBMZGZ-SHYZEUOFSA-N 2'‐deoxycytidine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 CKTSBUTUHBMZGZ-SHYZEUOFSA-N 0.000 description 2
- FZWGECJQACGGTI-UHFFFAOYSA-N 2-amino-7-methyl-1,7-dihydro-6H-purin-6-one Chemical compound NC1=NC(O)=C2N(C)C=NC2=N1 FZWGECJQACGGTI-UHFFFAOYSA-N 0.000 description 2
- ASJSAQIRZKANQN-CRCLSJGQSA-N 2-deoxy-D-ribose Chemical compound OC[C@@H](O)[C@@H](O)CC=O ASJSAQIRZKANQN-CRCLSJGQSA-N 0.000 description 2
- OIVLITBTBDPEFK-UHFFFAOYSA-N 5,6-dihydrouracil Chemical compound O=C1CCNC(=O)N1 OIVLITBTBDPEFK-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 239000004475 Arginine Substances 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 2
- 102000005381 Cytidine Deaminase Human genes 0.000 description 2
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 2
- CKTSBUTUHBMZGZ-UHFFFAOYSA-N Deoxycytidine Natural products O=C1N=C(N)C=CN1C1OC(CO)C(O)C1 CKTSBUTUHBMZGZ-UHFFFAOYSA-N 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 101150106478 GPS1 gene Proteins 0.000 description 2
- 108091005461 Nucleic proteins Chemical group 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 241000251745 Petromyzon marinus Species 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 229930185560 Pseudouridine Natural products 0.000 description 2
- PTJWIQPHWPFNBW-UHFFFAOYSA-N Pseudouridine C Natural products OC1C(O)C(CO)OC1C1=CNC(=O)NC1=O PTJWIQPHWPFNBW-UHFFFAOYSA-N 0.000 description 2
- 108020004682 Single-Stranded DNA Proteins 0.000 description 2
- 102100022433 Single-stranded DNA cytosine deaminase Human genes 0.000 description 2
- 239000012491 analyte Substances 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- WGDUUQDYDIIBKT-UHFFFAOYSA-N beta-Pseudouridine Natural products OC1OC(CN2C=CC(=O)NC2=O)C(O)C1O WGDUUQDYDIIBKT-UHFFFAOYSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 229940029575 guanosine Drugs 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000000051 modifying effect Effects 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 2
- 150000004713 phosphodiesters Chemical class 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- PTJWIQPHWPFNBW-GBNDHIKLSA-N pseudouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1C1=CNC(=O)NC1=O PTJWIQPHWPFNBW-GBNDHIKLSA-N 0.000 description 2
- 125000004219 purine nucleobase group Chemical group 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 2
- RIFDKYBNWNPCQK-IOSLPCCCSA-N (2r,3s,4r,5r)-2-(hydroxymethyl)-5-(6-imino-3-methylpurin-9-yl)oxolane-3,4-diol Chemical compound C1=2N(C)C=NC(=N)C=2N=CN1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O RIFDKYBNWNPCQK-IOSLPCCCSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
- RKSLVDIXBGWPIS-UAKXSSHOSA-N 1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-iodopyrimidine-2,4-dione Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 RKSLVDIXBGWPIS-UAKXSSHOSA-N 0.000 description 1
- QLOCVMVCRJOTTM-TURQNECASA-N 1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-prop-1-ynylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C#CC)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 QLOCVMVCRJOTTM-TURQNECASA-N 0.000 description 1
- PISWNSOQFZRVJK-XLPZGREQSA-N 1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-2-sulfanylidenepyrimidin-4-one Chemical compound S=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 PISWNSOQFZRVJK-XLPZGREQSA-N 0.000 description 1
- UVBYMVOUBXYSFV-XUTVFYLZSA-N 1-methylpseudouridine Chemical compound O=C1NC(=O)N(C)C=C1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 UVBYMVOUBXYSFV-XUTVFYLZSA-N 0.000 description 1
- VGONTNSXDCQUGY-RRKCRQDMSA-N 2'-deoxyinosine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC2=O)=C2N=C1 VGONTNSXDCQUGY-RRKCRQDMSA-N 0.000 description 1
- MXHRCPNRJAMMIM-SHYZEUOFSA-N 2'-deoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 MXHRCPNRJAMMIM-SHYZEUOFSA-N 0.000 description 1
- JRYMOPZHXMVHTA-DAGMQNCNSA-N 2-amino-7-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1h-pyrrolo[2,3-d]pyrimidin-4-one Chemical compound C1=CC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O JRYMOPZHXMVHTA-DAGMQNCNSA-N 0.000 description 1
- RHFUOMFWUGWKKO-XVFCMESISA-N 2-thiocytidine Chemical compound S=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 RHFUOMFWUGWKKO-XVFCMESISA-N 0.000 description 1
- XXSIICQLPUAUDF-TURQNECASA-N 4-amino-1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-prop-1-ynylpyrimidin-2-one Chemical compound O=C1N=C(N)C(C#CC)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 XXSIICQLPUAUDF-TURQNECASA-N 0.000 description 1
- AGFIRQJZCNVMCW-UAKXSSHOSA-N 5-bromouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 AGFIRQJZCNVMCW-UAKXSSHOSA-N 0.000 description 1
- FHIDNBAQOFJWCA-UAKXSSHOSA-N 5-fluorouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 FHIDNBAQOFJWCA-UAKXSSHOSA-N 0.000 description 1
- ZXIATBNUWJBBGT-JXOAFFINSA-N 5-methoxyuridine Chemical compound O=C1NC(=O)C(OC)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 ZXIATBNUWJBBGT-JXOAFFINSA-N 0.000 description 1
- KDOPAZIWBAHVJB-UHFFFAOYSA-N 5h-pyrrolo[3,2-d]pyrimidine Chemical compound C1=NC=C2NC=CC2=N1 KDOPAZIWBAHVJB-UHFFFAOYSA-N 0.000 description 1
- BXJHWYVXLGLDMZ-UHFFFAOYSA-N 6-O-methylguanine Chemical compound COC1=NC(N)=NC2=C1NC=N2 BXJHWYVXLGLDMZ-UHFFFAOYSA-N 0.000 description 1
- UEHOMUNTZPIBIL-UUOKFMHZSA-N 6-amino-9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-7h-purin-8-one Chemical compound O=C1NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O UEHOMUNTZPIBIL-UUOKFMHZSA-N 0.000 description 1
- OGHAROSJZRTIOK-KQYNXXCUSA-O 7-methylguanosine Chemical compound C1=2N=C(N)NC(=O)C=2[N+](C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OGHAROSJZRTIOK-KQYNXXCUSA-O 0.000 description 1
- HCAJQHYUCKICQH-VPENINKCSA-N 8-Oxo-7,8-dihydro-2'-deoxyguanosine Chemical compound C1=2NC(N)=NC(=O)C=2NC(=O)N1[C@H]1C[C@H](O)[C@@H](CO)O1 HCAJQHYUCKICQH-VPENINKCSA-N 0.000 description 1
- HDZZVAMISRMYHH-UHFFFAOYSA-N 9beta-Ribofuranosyl-7-deazaadenin Natural products C1=CC=2C(N)=NC=NC=2N1C1OC(CO)C(O)C1O HDZZVAMISRMYHH-UHFFFAOYSA-N 0.000 description 1
- 108010029988 AICDA (activation-induced cytidine deaminase) Proteins 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- 235000002198 Annona diversifolia Nutrition 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 101150018129 CSF2 gene Proteins 0.000 description 1
- 101150069031 CSN2 gene Proteins 0.000 description 1
- 241000282832 Camelidae Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 108091060290 Chromatid Proteins 0.000 description 1
- 102220584721 Coordinator of PRMT5 and differentiation stimulator_P48A_mutation Human genes 0.000 description 1
- 101150074775 Csf1 gene Proteins 0.000 description 1
- 102220503606 Cyclin-dependent kinase inhibitor 2A_P48L_mutation Human genes 0.000 description 1
- 230000007018 DNA scission Effects 0.000 description 1
- SHIBSTMRCDJXLN-UHFFFAOYSA-N Digoxigenin Natural products C1CC(C2C(C3(C)CCC(O)CC3CC2)CC2O)(O)C2(C)C1C1=CC(=O)OC1 SHIBSTMRCDJXLN-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 102100038132 Endogenous retrovirus group K member 6 Pro protein Human genes 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 102220637361 Glutathione S-transferase A3_I49V_mutation Human genes 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- UBORTCNDUKBEOP-UHFFFAOYSA-N L-xanthosine Natural products OC1C(O)C(CO)OC1N1C(NC(=O)NC2=O)=C2N=C1 UBORTCNDUKBEOP-UHFFFAOYSA-N 0.000 description 1
- 241000282838 Lama Species 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 101100219625 Mus musculus Casd1 gene Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 101100385413 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) csm-3 gene Proteins 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 101150044917 Prl3b1 gene Proteins 0.000 description 1
- 101150113550 Prl3d1 gene Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 230000004570 RNA-binding Effects 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 101100047461 Rattus norvegicus Trpm8 gene Proteins 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 101710143275 Single-stranded DNA cytosine deaminase Proteins 0.000 description 1
- 108020004688 Small Nuclear RNA Proteins 0.000 description 1
- 102000039471 Small Nuclear RNA Human genes 0.000 description 1
- 108020004459 Small interfering RNA Proteins 0.000 description 1
- 108091081024 Start codon Proteins 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- UBORTCNDUKBEOP-HAVMAKPUSA-N Xanthosine Natural products O[C@@H]1[C@H](O)[C@H](CO)O[C@H]1N1C(NC(=O)NC2=O)=C2N=C1 UBORTCNDUKBEOP-HAVMAKPUSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- 210000004507 artificial chromosome Anatomy 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 description 1
- 230000033590 base-excision repair Effects 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 239000003124 biologic agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 101150055766 cat gene Proteins 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000009614 chemical analysis method Methods 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000012707 chemical precursor Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 210000004756 chromatid Anatomy 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 101150055601 cops2 gene Proteins 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 101150037603 cst-1 gene Proteins 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- VGONTNSXDCQUGY-UHFFFAOYSA-N desoxyinosine Natural products C1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 VGONTNSXDCQUGY-UHFFFAOYSA-N 0.000 description 1
- MXHRCPNRJAMMIM-UHFFFAOYSA-N desoxyuridine Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 MXHRCPNRJAMMIM-UHFFFAOYSA-N 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- QONQRTHLHBTMGP-UHFFFAOYSA-N digitoxigenin Natural products CC12CCC(C3(CCC(O)CC3CC3)C)C3C11OC1CC2C1=CC(=O)OC1 QONQRTHLHBTMGP-UHFFFAOYSA-N 0.000 description 1
- SHIBSTMRCDJXLN-KCZCNTNESA-N digoxigenin Chemical compound C1([C@@H]2[C@@]3([C@@](CC2)(O)[C@H]2[C@@H]([C@@]4(C)CC[C@H](O)C[C@H]4CC2)C[C@H]3O)C)=CC(=O)OC1 SHIBSTMRCDJXLN-KCZCNTNESA-N 0.000 description 1
- ZPTBLXKRQACLCR-XVFCMESISA-N dihydrouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)CC1 ZPTBLXKRQACLCR-XVFCMESISA-N 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000003804 extraction from natural source Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 150000002402 hexoses Chemical class 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000000984 immunochemical effect Effects 0.000 description 1
- 230000008676 import Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000017730 intein-mediated protein splicing Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 239000003471 mutagenic agent Substances 0.000 description 1
- 231100000707 mutagenic chemical Toxicity 0.000 description 1
- 230000005257 nucleotidylation Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 235000019419 proteases Nutrition 0.000 description 1
- 108020001580 protein domains Proteins 0.000 description 1
- 230000016434 protein splicing Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 125000000548 ribosyl group Chemical group C1([C@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- DWRXFEITVBNRMK-JXOAFFINSA-N ribothymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 DWRXFEITVBNRMK-JXOAFFINSA-N 0.000 description 1
- RHFUOMFWUGWKKO-UHFFFAOYSA-N s2C Natural products S=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 RHFUOMFWUGWKKO-UHFFFAOYSA-N 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- HDZZVAMISRMYHH-KCGFPETGSA-N tubercidin Chemical compound C1=CC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O HDZZVAMISRMYHH-KCGFPETGSA-N 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- UBORTCNDUKBEOP-UUOKFMHZSA-N xanthosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(NC(=O)NC2=O)=C2N=C1 UBORTCNDUKBEOP-UUOKFMHZSA-N 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/78—Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
- C12N15/102—Mutagenizing nucleic acids
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/52—Genes encoding for enzymes or proenzymes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/62—DNA sequences coding for fusion proteins
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y305/00—Hydrolases acting on carbon-nitrogen bonds, other than peptide bonds (3.5)
- C12Y305/04—Hydrolases acting on carbon-nitrogen bonds, other than peptide bonds (3.5) in cyclic amidines (3.5.4)
- C12Y305/04004—Adenosine deaminase (3.5.4.4)
-
- 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
-
- 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]
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y305/00—Hydrolases acting on carbon-nitrogen bonds, other than peptide bonds (3.5)
- C12Y305/04—Hydrolases acting on carbon-nitrogen bonds, other than peptide bonds (3.5) in cyclic amidines (3.5.4)
- C12Y305/04005—Cytidine deaminase (3.5.4.5)
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Genetics & Genomics (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Biomedical Technology (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Medicinal Chemistry (AREA)
- Plant Pathology (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Crystallography & Structural Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Enzymes And Modification Thereof (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US202163166778P | 2021-03-26 | 2021-03-26 | |
| US63/166,778 | 2021-03-26 | ||
| US202163229057P | 2021-08-03 | 2021-08-03 | |
| US63/229,057 | 2021-08-03 | ||
| PCT/US2022/022050 WO2022204574A1 (en) | 2021-03-26 | 2022-03-25 | Adenosine deaminase variants and uses thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20240004276A true KR20240004276A (ko) | 2024-01-11 |
Family
ID=83397962
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020237033780A Pending KR20240004276A (ko) | 2021-03-26 | 2022-03-25 | 아데노신 데아미나아제 변이체 및 이의 용도 |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US20240158775A1 (https=) |
| EP (1) | EP4313118A4 (https=) |
| JP (1) | JP2024511163A (https=) |
| KR (1) | KR20240004276A (https=) |
| AU (1) | AU2022246176A1 (https=) |
| BR (1) | BR112023019539A2 (https=) |
| CA (1) | CA3214494A1 (https=) |
| WO (1) | WO2022204574A1 (https=) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020051562A2 (en) | 2018-09-07 | 2020-03-12 | Beam Therapeutics Inc. | Compositions and methods for improving base editing |
| EP3847254A4 (en) | 2018-09-07 | 2022-08-10 | Beam Therapeutics Inc. | COMPOSITIONS AND METHODS FOR DELIVERING A NUCLEOBASE EDITING SYSTEM |
| AU2020215730A1 (en) | 2019-01-31 | 2021-07-29 | Beam Therapeutics Inc. | Nucleobase editors having reduced non-target deamination and assays for characterizing nucleobase editors |
| CN120174005A (zh) | 2019-02-13 | 2025-06-20 | 比姆医疗股份有限公司 | 具有用于修饰靶标序列中核碱基的腺苷脱氨酶碱基编辑器的经修饰的免疫细胞 |
| EP4034138A4 (en) | 2019-09-27 | 2024-07-31 | Beam Therapeutics, Inc. | COMPOSITIONS AND METHODS FOR THE TREATMENT OF LIQUID CANCERS |
| CA3196831A1 (en) | 2020-09-25 | 2022-03-31 | Beam Therapeutics Inc. | Fratricide resistant modified immune cells and methods of using the same |
| EP4705444A2 (en) * | 2023-05-04 | 2026-03-11 | Technische Universität Dresden | Highly active crispr base editors obtained through cas-assisted substrate-linked directed evolution (caslide) |
| EP4458963A1 (en) * | 2023-05-04 | 2024-11-06 | Technische Universität Dresden | Highly active crispr base editors obtained through cas-assisted substrate-linked directed evolution (caslide) |
| CN120290534A (zh) * | 2024-01-10 | 2025-07-11 | 上海数因信科智能科技有限公司 | 腺嘌呤脱氨酶、包含其的碱基编辑器融合蛋白和碱基编辑器系统及其应用 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR112017007765B1 (pt) * | 2014-10-14 | 2023-10-03 | Halozyme, Inc | Composições de adenosina deaminase-2 (ada2), variantes do mesmo e métodos de usar o mesmo |
| AU2020215730A1 (en) * | 2019-01-31 | 2021-07-29 | Beam Therapeutics Inc. | Nucleobase editors having reduced non-target deamination and assays for characterizing nucleobase editors |
| WO2020160517A1 (en) * | 2019-01-31 | 2020-08-06 | Beam Therapeutics Inc. | Nucleobase editors having reduced off-target deamination and methods of using same to modify a nucleobase target sequence |
| WO2021022043A2 (en) * | 2019-07-30 | 2021-02-04 | Pairwise Plants Services, Inc. | Morphogenic regulators and methods of using the same |
| WO2021042062A2 (en) * | 2019-08-30 | 2021-03-04 | Joung J Keith | Combinatorial adenine and cytosine dna base editors |
| AU2020344547A1 (en) * | 2019-09-09 | 2022-03-24 | Beam Therapeutics Inc. | Novel nucleobase editors and methods of using same |
-
2022
- 2022-03-25 EP EP22776767.0A patent/EP4313118A4/en active Pending
- 2022-03-25 JP JP2023558765A patent/JP2024511163A/ja active Pending
- 2022-03-25 KR KR1020237033780A patent/KR20240004276A/ko active Pending
- 2022-03-25 BR BR112023019539A patent/BR112023019539A2/pt unknown
- 2022-03-25 CA CA3214494A patent/CA3214494A1/en active Pending
- 2022-03-25 AU AU2022246176A patent/AU2022246176A1/en active Pending
- 2022-03-25 WO PCT/US2022/022050 patent/WO2022204574A1/en not_active Ceased
-
2023
- 2023-09-26 US US18/474,969 patent/US20240158775A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| WO2022204574A1 (en) | 2022-09-29 |
| EP4313118A4 (en) | 2025-06-18 |
| CA3214494A1 (en) | 2022-09-29 |
| EP4313118A1 (en) | 2024-02-07 |
| BR112023019539A2 (pt) | 2023-12-05 |
| AU2022246176A1 (en) | 2023-10-05 |
| US20240158775A1 (en) | 2024-05-16 |
| JP2024511163A (ja) | 2024-03-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR20240004276A (ko) | 아데노신 데아미나아제 변이체 및 이의 용도 | |
| KR102852347B1 (ko) | 프로그래밍가능한 염기 편집기 시스템을 이용하여 병원성 아미노산을 치환하는 방법 | |
| KR20210055733A (ko) | 핵염기 편집 시스템을 전달하기 위한 조성물 및 방법 | |
| AU2019282149B2 (en) | RNA-guided nucleases and active fragments and variants thereof and methods of use | |
| CN120005859B (zh) | 治疗血红素病变的组合物和方法 | |
| JP7646552B2 (ja) | 低減された非標的脱アミノ化を有する核酸塩基エディターおよび核酸塩基エディターの特徴づけのためのアッセイ | |
| KR102827276B1 (ko) | 아데노신 핵염기 편집제 및 그의 용도 | |
| JP7418470B2 (ja) | オリジアス由来のトランスポザーゼを用いた核酸コンストラクトの真核細胞への組み込み | |
| JP7418469B2 (ja) | アミエロイス由来のトランスポザーゼを用いた核酸コンストラクトの真核生物のゲノムへの転移 | |
| KR20230014700A (ko) | Rna-가이드된 뉴클레아제 및 그의 활성 단편 및 변이체 및 사용 방법 | |
| KR20250107288A (ko) | 아데노신 염기 편집제의 용도 | |
| KR20210127206A (ko) | 유전성 질환의 치료를 위한 것을 포함하는, 아데노신 데아미나제 염기 편집기를 사용하여 질환-관련 유전자를 편집하는 방법 | |
| US20240287453A1 (en) | Persistent allogeneic modified immune cells and methods of use thereof | |
| CA3225808A1 (en) | Context-specific adenine base editors and uses thereof | |
| EP4229195A1 (en) | Compositions and methods for treating glycogen storage disease type 1a | |
| KR20240012377A (ko) | 염기 편집기의 자기-불활성화용 조성물 및 방법 | |
| CA3189662A1 (en) | Compositions comprising a nuclease and uses thereof | |
| KR102959498B1 (ko) | 프로그래밍가능한 염기 편집기 시스템을 이용하여 단일염기다형성을 편집하는 방법 | |
| KR102959497B1 (ko) | 프로그래밍가능한 염기 편집기 시스템을 이용하여 병원성 돌연변이를 억제하는 방법 | |
| HK40038501A (en) | Integration of nucleic acid constructs into eukaryotic cells with a transposase from oryzias | |
| KR20210023830A (ko) | 프로그래밍가능한 염기 편집기 시스템을 이용하여 병원성 돌연변이를 억제하는 방법 | |
| HK40038987A (en) | Transposition of nucleic acid constructs into eukaryotic genomes with a transposase from amyelois | |
| KR20210023832A (ko) | 프로그래밍가능한 염기 편집기 시스템을 이용하여 단일염기다형성을 편집하는 방법 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20231004 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| A201 | Request for examination | ||
| PA0201 | Request for examination |
Patent event code: PA02012R01D Patent event date: 20250324 Comment text: Request for Examination of Application |