EA036379B1 - Химерные антигенные рецепторы к bcma - Google Patents

Info

Publication number

EA036379B1

EA036379B1 EA201791310A EA201791310A EA036379B1 EA 036379 B1 EA036379 B1 EA 036379B1 EA 201791310 A EA201791310 A EA 201791310A EA 201791310 A EA201791310 A EA 201791310A EA 036379 B1 EA036379 B1 EA 036379B1

Authority

EA

Eurasian Patent Office

Prior art keywords

cells

cell

vector

car

sequence

Prior art date

2014-12-12

Links

• Espacenet
• Global Dossier
• Discuss

• 108010008014 B-Cell Maturation Antigen Proteins 0.000 title claims abstract description 67
• 102000006942 B-Cell Maturation Antigen Human genes 0.000 title claims abstract description 62
• BGFTWECWAICPDG-UHFFFAOYSA-N 2-[bis(4-chlorophenyl)methyl]-4-n-[3-[bis(4-chlorophenyl)methyl]-4-(dimethylamino)phenyl]-1-n,1-n-dimethylbenzene-1,4-diamine Chemical compound C1=C(C(C=2C=CC(Cl)=CC=2)C=2C=CC(Cl)=CC=2)C(N(C)C)=CC=C1NC(C=1)=CC=C(N(C)C)C=1C(C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 BGFTWECWAICPDG-UHFFFAOYSA-N 0.000 title abstract 2
• 102000005962 receptors Human genes 0.000 title description 7
• 108020003175 receptors Proteins 0.000 title description 7
• 230000000890 antigenic effect Effects 0.000 title description 4
• 108010019670 Chimeric Antigen Receptors Proteins 0.000 claims abstract description 211
• 239000013598 vector Substances 0.000 claims abstract description 135
• 102000040430 polynucleotide Human genes 0.000 claims abstract description 117
• 108091033319 polynucleotide Proteins 0.000 claims abstract description 117
• 239000002157 polynucleotide Substances 0.000 claims abstract description 117
• 239000012642 immune effector Substances 0.000 claims abstract description 77
• 229940121354 immunomodulator Drugs 0.000 claims abstract description 77
• 239000000203 mixture Substances 0.000 claims abstract description 34
• 238000004519 manufacturing process Methods 0.000 claims abstract description 14
• 238000011467 adoptive cell therapy Methods 0.000 claims abstract description 5
• 210000004027 cell Anatomy 0.000 claims description 346
• 210000001744 T-lymphocyte Anatomy 0.000 claims description 275
• 241000700605 Viruses Species 0.000 claims description 70
• 230000001177 retroviral effect Effects 0.000 claims description 39
• 125000003275 alpha amino acid group Chemical group 0.000 claims description 29
• 239000013603 viral vector Substances 0.000 claims description 27
• 238000006467 substitution reaction Methods 0.000 claims description 24
• 241001430294 unidentified retrovirus Species 0.000 claims description 21
• 238000012217 deletion Methods 0.000 claims description 20
• 230000037430 deletion Effects 0.000 claims description 20
• 241000713772 Human immunodeficiency virus 1 Species 0.000 claims description 15
• 230000004048 modification Effects 0.000 claims description 13
• 238000012986 modification Methods 0.000 claims description 13
• 238000003780 insertion Methods 0.000 claims description 10
• 230000037431 insertion Effects 0.000 claims description 10
• 241000282693 Cercopithecidae Species 0.000 claims description 7
• 241000713800 Feline immunodeficiency virus Species 0.000 claims description 7
• 241000713340 Human immunodeficiency virus 2 Species 0.000 claims description 7
• 241000713704 Bovine immunodeficiency virus Species 0.000 claims description 6
• 206010014599 encephalitis Diseases 0.000 claims description 4
• 238000012856 packing Methods 0.000 claims description 4
• 241000283707 Capra Species 0.000 claims description 3
• 241000713730 Equine infectious anemia virus Species 0.000 claims description 3
• 206010061598 Immunodeficiency Diseases 0.000 claims description 3
• 208000029462 Immunodeficiency disease Diseases 0.000 claims description 3
• 208000010094 Visna Diseases 0.000 claims description 3
• 206010003246 arthritis Diseases 0.000 claims description 3
• 230000007813 immunodeficiency Effects 0.000 claims description 3
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
• 108090000765 processed proteins & peptides Proteins 0.000 description 169
• 102000004196 processed proteins & peptides Human genes 0.000 description 160
• 229920001184 polypeptide Polymers 0.000 description 153
• 108090000623 proteins and genes Proteins 0.000 description 127
• 230000027455 binding Effects 0.000 description 107
• 239000000427 antigen Substances 0.000 description 76
• 108091007433 antigens Proteins 0.000 description 76
• 102000036639 antigens Human genes 0.000 description 76
• 238000000034 method Methods 0.000 description 75
• 230000014509 gene expression Effects 0.000 description 67
• 239000012634 fragment Substances 0.000 description 63
• 235000001014 amino acid Nutrition 0.000 description 59
• 102000004169 proteins and genes Human genes 0.000 description 56
• 229940024606 amino acid Drugs 0.000 description 53
• 230000011664 signaling Effects 0.000 description 53
• 150000001413 amino acids Chemical class 0.000 description 52
• 108091007960 PI3Ks Proteins 0.000 description 50
• 235000018102 proteins Nutrition 0.000 description 50
• 210000003719 b-lymphocyte Anatomy 0.000 description 49
• 102000038030 PI3Ks Human genes 0.000 description 48
• 230000000694 effects Effects 0.000 description 46
• 239000003112 inhibitor Substances 0.000 description 46
• 150000007523 nucleic acids Chemical class 0.000 description 42
• 230000037361 pathway Effects 0.000 description 42
• 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 40
• 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 40
• 102000039446 nucleic acids Human genes 0.000 description 40
• 108020004707 nucleic acids Proteins 0.000 description 40
• 108091008611 Protein Kinase B Proteins 0.000 description 38
• 230000004913 activation Effects 0.000 description 37
• 230000003612 virological effect Effects 0.000 description 37
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 36
• 239000003795 chemical substances by application Substances 0.000 description 36
• 241000699666 Mus <mouse, genus> Species 0.000 description 35
• 108020004414 DNA Proteins 0.000 description 33
• 101000716102 Homo sapiens T-cell surface glycoprotein CD4 Proteins 0.000 description 32
• 206010028980 Neoplasm Diseases 0.000 description 32
• 239000012828 PI3K inhibitor Substances 0.000 description 32
• 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 description 32
• 229940043441 phosphoinositide 3-kinase inhibitor Drugs 0.000 description 32
• 101001018097 Homo sapiens L-selectin Proteins 0.000 description 31
• 102100033467 L-selectin Human genes 0.000 description 31
• 239000002773 nucleotide Substances 0.000 description 31
• 238000004806 packaging method and process Methods 0.000 description 31
• 125000003729 nucleotide group Chemical group 0.000 description 30
• 230000035755 proliferation Effects 0.000 description 30
• 101000946843 Homo sapiens T-cell surface glycoprotein CD8 alpha chain Proteins 0.000 description 25
• 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 description 25
• 230000000139 costimulatory effect Effects 0.000 description 25
• 102100036301 C-C chemokine receptor type 7 Human genes 0.000 description 24
• 101000716065 Homo sapiens C-C chemokine receptor type 7 Proteins 0.000 description 24
• 102100022153 Tumor necrosis factor receptor superfamily member 4 Human genes 0.000 description 23
• 101000851370 Homo sapiens Tumor necrosis factor receptor superfamily member 9 Proteins 0.000 description 22
• 102000000588 Interleukin-2 Human genes 0.000 description 22
• 108010002350 Interleukin-2 Proteins 0.000 description 22
• 102100037906 T-cell surface glycoprotein CD3 zeta chain Human genes 0.000 description 22
• 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 description 22
• 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 22
• 102100036856 Tumor necrosis factor receptor superfamily member 9 Human genes 0.000 description 22
• 239000003623 enhancer Substances 0.000 description 22
• 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 22
• 101001043809 Homo sapiens Interleukin-7 receptor subunit alpha Proteins 0.000 description 21
• 102100021593 Interleukin-7 receptor subunit alpha Human genes 0.000 description 21
• 102100033810 RAC-alpha serine/threonine-protein kinase Human genes 0.000 description 21
• 230000008488 polyadenylation Effects 0.000 description 21
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 20
• 230000006870 function Effects 0.000 description 20
• 239000002679 microRNA Substances 0.000 description 20
• 239000002245 particle Substances 0.000 description 20
• 230000001105 regulatory effect Effects 0.000 description 20
• 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 19
• 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 description 19
• -1 CD8a Proteins 0.000 description 19
• 108010047041 Complementarity Determining Regions Proteins 0.000 description 19
• 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 description 19
• 101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 description 19
• 239000004365 Protease Substances 0.000 description 19
• 108020004999 messenger RNA Proteins 0.000 description 19
• 238000012546 transfer Methods 0.000 description 19
• 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 description 18
• 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 description 18
• 101000738335 Homo sapiens T-cell surface glycoprotein CD3 zeta chain Proteins 0.000 description 18
• 108091005804 Peptidases Proteins 0.000 description 18
• 239000012636 effector Substances 0.000 description 18
• 108091070501 miRNA Proteins 0.000 description 18
• 230000004936 stimulating effect Effects 0.000 description 18
• 101000679851 Homo sapiens Tumor necrosis factor receptor superfamily member 4 Proteins 0.000 description 17
• 108060003951 Immunoglobulin Proteins 0.000 description 17
• 206010035226 Plasma cell myeloma Diseases 0.000 description 17
• 238000003776 cleavage reaction Methods 0.000 description 17
• 102000018358 immunoglobulin Human genes 0.000 description 17
• 102000004127 Cytokines Human genes 0.000 description 16
• 108090000695 Cytokines Proteins 0.000 description 16
• 102100034349 Integrase Human genes 0.000 description 16
• 241000713666 Lentivirus Species 0.000 description 16
• 238000000338 in vitro Methods 0.000 description 16
• 230000004068 intracellular signaling Effects 0.000 description 16
• 239000003446 ligand Substances 0.000 description 16
• 230000007017 scission Effects 0.000 description 16
• 201000011510 cancer Diseases 0.000 description 15
• 208000015181 infectious disease Diseases 0.000 description 15
• 230000003834 intracellular effect Effects 0.000 description 15
• 239000013612 plasmid Substances 0.000 description 15
• 238000011282 treatment Methods 0.000 description 15
• 102100027207 CD27 antigen Human genes 0.000 description 14
• 101000914511 Homo sapiens CD27 antigen Proteins 0.000 description 14
• 101001137987 Homo sapiens Lymphocyte activation gene 3 protein Proteins 0.000 description 14
• 102000017578 LAG3 Human genes 0.000 description 14
• 108020004459 Small interfering RNA Proteins 0.000 description 14
• 239000013604 expression vector Substances 0.000 description 14
• 230000001976 improved effect Effects 0.000 description 14
• 238000001727 in vivo Methods 0.000 description 14
• 230000002401 inhibitory effect Effects 0.000 description 14
• 239000003197 protein kinase B inhibitor Substances 0.000 description 14
• 230000000638 stimulation Effects 0.000 description 14
• 238000013518 transcription Methods 0.000 description 14
• 230000035897 transcription Effects 0.000 description 14
• 101710117290 Aldo-keto reductase family 1 member C4 Proteins 0.000 description 13
• 108090000994 Catalytic RNA Proteins 0.000 description 13
• 102000053642 Catalytic RNA Human genes 0.000 description 13
• 101000934346 Homo sapiens T-cell surface antigen CD2 Proteins 0.000 description 13
• 241000725303 Human immunodeficiency virus Species 0.000 description 13
• 102100025237 T-cell surface antigen CD2 Human genes 0.000 description 13
• 108091093126 WHP Posttrascriptional Response Element Proteins 0.000 description 13
• HGVNLRPZOWWDKD-UHFFFAOYSA-N ZSTK-474 Chemical group FC(F)C1=NC2=CC=CC=C2N1C(N=1)=NC(N2CCOCC2)=NC=1N1CCOCC1 HGVNLRPZOWWDKD-UHFFFAOYSA-N 0.000 description 13
• 238000007792 addition Methods 0.000 description 13
• 230000010076 replication Effects 0.000 description 13
• 108091092562 ribozyme Proteins 0.000 description 13
• 230000009870 specific binding Effects 0.000 description 13
• 230000009258 tissue cross reactivity Effects 0.000 description 13
• 238000010361 transduction Methods 0.000 description 13
• 230000026683 transduction Effects 0.000 description 13
• 241000701022 Cytomegalovirus Species 0.000 description 12
• 239000011230 binding agent Substances 0.000 description 12
• 230000000295 complement effect Effects 0.000 description 12
• 108020001507 fusion proteins Proteins 0.000 description 12
• 102000037865 fusion proteins Human genes 0.000 description 12
• 230000001939 inductive effect Effects 0.000 description 12
• 239000000047 product Substances 0.000 description 12
• 230000006798 recombination Effects 0.000 description 12
• 238000005215 recombination Methods 0.000 description 12
• 238000010561 standard procedure Methods 0.000 description 12
• 102000008135 Mechanistic Target of Rapamycin Complex 1 Human genes 0.000 description 11
• 108010035196 Mechanistic Target of Rapamycin Complex 1 Proteins 0.000 description 11
• 208000034578 Multiple myelomas Diseases 0.000 description 11
• 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 description 11
• 102100024213 Programmed cell death 1 ligand 2 Human genes 0.000 description 11
• 108091027967 Small hairpin RNA Proteins 0.000 description 11
• 108020004440 Thymidine kinase Proteins 0.000 description 11
• 102100028785 Tumor necrosis factor receptor superfamily member 14 Human genes 0.000 description 11
• 230000004071 biological effect Effects 0.000 description 11
• 230000005754 cellular signaling Effects 0.000 description 11
• 150000001875 compounds Chemical class 0.000 description 11
• 238000012239 gene modification Methods 0.000 description 11
• 230000005017 genetic modification Effects 0.000 description 11
• 235000013617 genetically modified food Nutrition 0.000 description 11
• 230000010354 integration Effects 0.000 description 11
• 239000004055 small Interfering RNA Substances 0.000 description 11
• 230000014616 translation Effects 0.000 description 11
• 241001529453 unidentified herpesvirus Species 0.000 description 11
• 108010061833 Integrases Proteins 0.000 description 10
• 102000009308 Mechanistic Target of Rapamycin Complex 2 Human genes 0.000 description 10
• 108010034057 Mechanistic Target of Rapamycin Complex 2 Proteins 0.000 description 10
• 241000699670 Mus sp. Species 0.000 description 10
• 102000035195 Peptidases Human genes 0.000 description 10
• 102100040678 Programmed cell death protein 1 Human genes 0.000 description 10
• 102100029215 Signaling lymphocytic activation molecule Human genes 0.000 description 10
• 102000006601 Thymidine Kinase Human genes 0.000 description 10
• 230000001965 increasing effect Effects 0.000 description 10
• 230000001404 mediated effect Effects 0.000 description 10
• 230000001124 posttranscriptional effect Effects 0.000 description 10
• 125000006850 spacer group Chemical group 0.000 description 10
• 102100038080 B-cell receptor CD22 Human genes 0.000 description 9
• 108091007741 Chimeric antigen receptor T cells Proteins 0.000 description 9
• 239000004471 Glycine Substances 0.000 description 9
• 101000884305 Homo sapiens B-cell receptor CD22 Proteins 0.000 description 9
• 101000946860 Homo sapiens T-cell surface glycoprotein CD3 epsilon chain Proteins 0.000 description 9
• 101000801255 Homo sapiens Tumor necrosis factor receptor superfamily member 17 Proteins 0.000 description 9
• 241000701044 Human gammaherpesvirus 4 Species 0.000 description 9
• 108010021625 Immunoglobulin Fragments Proteins 0.000 description 9
• 102000008394 Immunoglobulin Fragments Human genes 0.000 description 9
• 102100037850 Interferon gamma Human genes 0.000 description 9
• 108010074328 Interferon-gamma Proteins 0.000 description 9
• 241000700584 Simplexvirus Species 0.000 description 9
• 102100035794 T-cell surface glycoprotein CD3 epsilon chain Human genes 0.000 description 9
• 230000015572 biosynthetic process Effects 0.000 description 9
• 230000001413 cellular effect Effects 0.000 description 9
• 230000005764 inhibitory process Effects 0.000 description 9
• 241000894007 species Species 0.000 description 9
• 230000008685 targeting Effects 0.000 description 9
• 230000001225 therapeutic effect Effects 0.000 description 9
• 210000001519 tissue Anatomy 0.000 description 9
• 238000001890 transfection Methods 0.000 description 9
• 238000013519 translation Methods 0.000 description 9
• MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 8
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
• 102100038132 Endogenous retrovirus group K member 6 Pro protein Human genes 0.000 description 8
• 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 8
• 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 8
• 101000914496 Homo sapiens T-cell antigen CD7 Proteins 0.000 description 8
• 108091028043 Nucleic acid sequence Proteins 0.000 description 8
• 108010077524 Peptide Elongation Factor 1 Proteins 0.000 description 8
• 108010076504 Protein Sorting Signals Proteins 0.000 description 8
• 102000018120 Recombinases Human genes 0.000 description 8
• 108010091086 Recombinases Proteins 0.000 description 8
• 241000714474 Rous sarcoma virus Species 0.000 description 8
• 108091008874 T cell receptors Proteins 0.000 description 8
• 102100027208 T-cell antigen CD7 Human genes 0.000 description 8
• 125000000539 amino acid group Chemical group 0.000 description 8
• 230000000875 corresponding effect Effects 0.000 description 8
• 230000007423 decrease Effects 0.000 description 8
• 230000004069 differentiation Effects 0.000 description 8
• 230000002068 genetic effect Effects 0.000 description 8
• 229940124302 mTOR inhibitor Drugs 0.000 description 8
• 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 description 8
• 239000003550 marker Substances 0.000 description 8
• 230000035772 mutation Effects 0.000 description 8
• 235000019419 proteases Nutrition 0.000 description 8
• 102100034540 Adenomatous polyposis coli protein Human genes 0.000 description 7
• 229940126638 Akt inhibitor Drugs 0.000 description 7
• 101150013553 CD40 gene Proteins 0.000 description 7
• 102100035793 CD83 antigen Human genes 0.000 description 7
• 102000004190 Enzymes Human genes 0.000 description 7
• 108090000790 Enzymes Proteins 0.000 description 7
• 101000924577 Homo sapiens Adenomatous polyposis coli protein Proteins 0.000 description 7
• 101000946856 Homo sapiens CD83 antigen Proteins 0.000 description 7
• XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 7
• AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 7
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 7
• 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 7
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 7
• 108010029485 Protein Isoforms Proteins 0.000 description 7
• 102000001708 Protein Isoforms Human genes 0.000 description 7
• 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 7
• 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 7
• 230000003213 activating effect Effects 0.000 description 7
• 238000002617 apheresis Methods 0.000 description 7
• 230000003197 catalytic effect Effects 0.000 description 7
• 235000018417 cysteine Nutrition 0.000 description 7
• 230000001472 cytotoxic effect Effects 0.000 description 7
• 229940088598 enzyme Drugs 0.000 description 7
• 210000002443 helper t lymphocyte Anatomy 0.000 description 7
• 102000046935 human TNFRSF17 Human genes 0.000 description 7
• 230000002458 infectious effect Effects 0.000 description 7
• 239000012212 insulator Substances 0.000 description 7
• 230000036210 malignancy Effects 0.000 description 7
• 210000003071 memory t lymphocyte Anatomy 0.000 description 7
• 210000000822 natural killer cell Anatomy 0.000 description 7
• 230000026731 phosphorylation Effects 0.000 description 7
• 238000006366 phosphorylation reaction Methods 0.000 description 7
• 238000002360 preparation method Methods 0.000 description 7
• 239000000126 substance Substances 0.000 description 7
• 238000003786 synthesis reaction Methods 0.000 description 7
• 108010074708 B7-H1 Antigen Proteins 0.000 description 6
• 108091026890 Coding region Proteins 0.000 description 6
• 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 6
• 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 description 6
• 108010061593 Member 14 Tumor Necrosis Factor Receptors Proteins 0.000 description 6
• 241001465754 Metazoa Species 0.000 description 6
• 101100407308 Mus musculus Pdcd1lg2 gene Proteins 0.000 description 6
• 102000010292 Peptide Elongation Factor 1 Human genes 0.000 description 6
• 108700030875 Programmed Cell Death 1 Ligand 2 Proteins 0.000 description 6
• 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 6
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 6
• 108010052160 Site-specific recombinase Proteins 0.000 description 6
• 101710165473 Tumor necrosis factor receptor superfamily member 4 Proteins 0.000 description 6
• 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 description 6
• 230000000692 anti-sense effect Effects 0.000 description 6
• 210000000612 antigen-presenting cell Anatomy 0.000 description 6
• 239000000090 biomarker Substances 0.000 description 6
• 210000004369 blood Anatomy 0.000 description 6
• 239000008280 blood Substances 0.000 description 6
• 238000001816 cooling Methods 0.000 description 6
• 239000002577 cryoprotective agent Substances 0.000 description 6
• 230000001419 dependent effect Effects 0.000 description 6
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
• 238000000684 flow cytometry Methods 0.000 description 6
• 230000004927 fusion Effects 0.000 description 6
• 239000001963 growth medium Substances 0.000 description 6
• 230000006698 induction Effects 0.000 description 6
• 230000003993 interaction Effects 0.000 description 6
• 210000004698 lymphocyte Anatomy 0.000 description 6
• 210000001616 monocyte Anatomy 0.000 description 6
• 210000000581 natural killer T-cell Anatomy 0.000 description 6
• 239000002777 nucleoside Substances 0.000 description 6
• 238000003860 storage Methods 0.000 description 6
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 6
• 230000029812 viral genome replication Effects 0.000 description 6
• 108010083359 Antigen Receptors Proteins 0.000 description 5
• 102000006306 Antigen Receptors Human genes 0.000 description 5
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 5
• 102100032937 CD40 ligand Human genes 0.000 description 5
• 102100037904 CD9 antigen Human genes 0.000 description 5
• 102100024965 Caspase recruitment domain-containing protein 11 Human genes 0.000 description 5
• 238000002965 ELISA Methods 0.000 description 5
• 101710091045 Envelope protein Proteins 0.000 description 5
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
• 102100029360 Hematopoietic cell signal transducer Human genes 0.000 description 5
• 102100021519 Hemoglobin subunit beta Human genes 0.000 description 5
• 108091005904 Hemoglobin subunit beta Proteins 0.000 description 5
• 102100026122 High affinity immunoglobulin gamma Fc receptor I Human genes 0.000 description 5
• 101000738354 Homo sapiens CD9 antigen Proteins 0.000 description 5
• 101000761179 Homo sapiens Caspase recruitment domain-containing protein 11 Proteins 0.000 description 5
• 101000990188 Homo sapiens Hematopoietic cell signal transducer Proteins 0.000 description 5
• 101000913074 Homo sapiens High affinity immunoglobulin gamma Fc receptor I Proteins 0.000 description 5
• 101000599852 Homo sapiens Intercellular adhesion molecule 1 Proteins 0.000 description 5
• 101000777628 Homo sapiens Leukocyte antigen CD37 Proteins 0.000 description 5
• 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 5
• 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 5
• 101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 description 5
• 101000934341 Homo sapiens T-cell surface glycoprotein CD5 Proteins 0.000 description 5
• 101000818543 Homo sapiens Tyrosine-protein kinase ZAP-70 Proteins 0.000 description 5
• 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 5
• 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 5
• 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 description 5
• DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 5
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 5
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 5
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 5
• COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 5
• 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 5
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 5
• 102100031586 Leukocyte antigen CD37 Human genes 0.000 description 5
• 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 description 5
• 102100034709 Lymphocyte cytosolic protein 2 Human genes 0.000 description 5
• 101710195102 Lymphocyte cytosolic protein 2 Proteins 0.000 description 5
• 102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 description 5
• 102000004473 OX40 Ligand Human genes 0.000 description 5
• 108010042215 OX40 Ligand Proteins 0.000 description 5
• 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 5
• 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 description 5
• 101710188315 Protein X Proteins 0.000 description 5
• 206010037660 Pyrexia Diseases 0.000 description 5
• 108010074687 Signaling Lymphocytic Activation Molecule Family Member 1 Proteins 0.000 description 5
• 102100025244 T-cell surface glycoprotein CD5 Human genes 0.000 description 5
• AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 5
• 239000004473 Threonine Substances 0.000 description 5
• 108010023649 Tripartite Motif Proteins Proteins 0.000 description 5
• 102000011408 Tripartite Motif Proteins Human genes 0.000 description 5
• QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 5
• 102100032101 Tumor necrosis factor ligand superfamily member 9 Human genes 0.000 description 5
• 102100021125 Tyrosine-protein kinase ZAP-70 Human genes 0.000 description 5
• 238000010367 cloning Methods 0.000 description 5
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 5
• 230000002950 deficient Effects 0.000 description 5
• 238000013461 design Methods 0.000 description 5
• 239000012091 fetal bovine serum Substances 0.000 description 5
• 230000009368 gene silencing by RNA Effects 0.000 description 5
• 239000003102 growth factor Substances 0.000 description 5
• 208000032839 leukemia Diseases 0.000 description 5
• 210000004962 mammalian cell Anatomy 0.000 description 5
• 239000002609 medium Substances 0.000 description 5
• 201000000050 myeloid neoplasm Diseases 0.000 description 5
• 108700004029 pol Genes Proteins 0.000 description 5
• 229920000642 polymer Polymers 0.000 description 5
• 238000012545 processing Methods 0.000 description 5
• 230000028327 secretion Effects 0.000 description 5
• 210000002966 serum Anatomy 0.000 description 5
• 239000004475 Arginine Substances 0.000 description 4
• DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 4
• 208000023275 Autoimmune disease Diseases 0.000 description 4
• 208000011691 Burkitt lymphomas Diseases 0.000 description 4
• 102100024263 CD160 antigen Human genes 0.000 description 4
• 102100025466 Carcinoembryonic antigen-related cell adhesion molecule 3 Human genes 0.000 description 4
• 108020004705 Codon Proteins 0.000 description 4
• 108020004635 Complementary DNA Proteins 0.000 description 4
• 108010080611 Cytosine Deaminase Proteins 0.000 description 4
• 102000000311 Cytosine Deaminase Human genes 0.000 description 4
• 241000714165 Feline leukemia virus Species 0.000 description 4
• 229920001917 Ficoll Polymers 0.000 description 4
• 241000711950 Filoviridae Species 0.000 description 4
• 102100021260 Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 1 Human genes 0.000 description 4
• 102000006354 HLA-DR Antigens Human genes 0.000 description 4
• 108010058597 HLA-DR Antigens Proteins 0.000 description 4
• 102100034458 Hepatitis A virus cellular receptor 2 Human genes 0.000 description 4
• 241000700721 Hepatitis B virus Species 0.000 description 4
• 101000761938 Homo sapiens CD160 antigen Proteins 0.000 description 4
• 101100112778 Homo sapiens CD247 gene Proteins 0.000 description 4
• 101000914337 Homo sapiens Carcinoembryonic antigen-related cell adhesion molecule 3 Proteins 0.000 description 4
• 101000894906 Homo sapiens Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 1 Proteins 0.000 description 4
• 101001068133 Homo sapiens Hepatitis A virus cellular receptor 2 Proteins 0.000 description 4
• 101000884270 Homo sapiens Natural killer cell receptor 2B4 Proteins 0.000 description 4
• 102000003812 Interleukin-15 Human genes 0.000 description 4
• 108010002586 Interleukin-7 Proteins 0.000 description 4
• 102100021592 Interleukin-7 Human genes 0.000 description 4
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 4
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 4
• HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 4
• AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 4
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 4
• FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 4
• KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 4
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 4
• 108700011259 MicroRNAs Proteins 0.000 description 4
• 101100226902 Mus musculus Fcrlb gene Proteins 0.000 description 4
• 102100038082 Natural killer cell receptor 2B4 Human genes 0.000 description 4
• 241000283973 Oryctolagus cuniculus Species 0.000 description 4
• 102100028251 Phosphoglycerate kinase 1 Human genes 0.000 description 4
• 101710139464 Phosphoglycerate kinase 1 Proteins 0.000 description 4
• 101710089372 Programmed cell death protein 1 Proteins 0.000 description 4
• 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 4
• 108020004511 Recombinant DNA Proteins 0.000 description 4
• 108010003723 Single-Domain Antibodies Proteins 0.000 description 4
• 241000251131 Sphyrna Species 0.000 description 4
• KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 4
• 241000711975 Vesicular stomatitis virus Species 0.000 description 4
• 230000009471 action Effects 0.000 description 4
• 239000012190 activator Substances 0.000 description 4
• 235000004279 alanine Nutrition 0.000 description 4
• 230000000735 allogeneic effect Effects 0.000 description 4
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 4
• 229960001230 asparagine Drugs 0.000 description 4
• 235000009582 asparagine Nutrition 0.000 description 4
• 239000000872 buffer Substances 0.000 description 4
• 238000010804 cDNA synthesis Methods 0.000 description 4
• 230000004663 cell proliferation Effects 0.000 description 4
• 230000008859 change Effects 0.000 description 4
• 239000002299 complementary DNA Substances 0.000 description 4
• 238000005138 cryopreservation Methods 0.000 description 4
• 238000012258 culturing Methods 0.000 description 4
• 239000003814 drug Substances 0.000 description 4
• 210000003743 erythrocyte Anatomy 0.000 description 4
• 238000009472 formulation Methods 0.000 description 4
• 238000007710 freezing Methods 0.000 description 4
• 230000008014 freezing Effects 0.000 description 4
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 4
• 230000012010 growth Effects 0.000 description 4
• 210000003958 hematopoietic stem cell Anatomy 0.000 description 4
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 4
• 238000009169 immunotherapy Methods 0.000 description 4
• 150000002632 lipids Chemical class 0.000 description 4
• 239000007788 liquid Substances 0.000 description 4
• 230000007774 longterm Effects 0.000 description 4
• 229930182817 methionine Natural products 0.000 description 4
• 229910052757 nitrogen Inorganic materials 0.000 description 4
• COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 4
• 101150088264 pol gene Proteins 0.000 description 4
• 230000008569 process Effects 0.000 description 4
• 238000010839 reverse transcription Methods 0.000 description 4
• 230000002441 reversible effect Effects 0.000 description 4
• 238000000926 separation method Methods 0.000 description 4
• 239000000243 solution Substances 0.000 description 4
• 239000000758 substrate Substances 0.000 description 4
• 230000004083 survival effect Effects 0.000 description 4
• 239000004474 valine Substances 0.000 description 4
• 238000005406 washing Methods 0.000 description 4
• 108010082808 4-1BB Ligand Proteins 0.000 description 3
• 108010024223 Adenine phosphoribosyltransferase Proteins 0.000 description 3
• 102100029457 Adenine phosphoribosyltransferase Human genes 0.000 description 3
• 108700028369 Alleles Proteins 0.000 description 3
• 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 3
• 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 3
• 102000001398 Granzyme Human genes 0.000 description 3
• 108060005986 Granzyme Proteins 0.000 description 3
• 206010061192 Haemorrhagic fever Diseases 0.000 description 3
• 208000017604 Hodgkin disease Diseases 0.000 description 3
• 208000021519 Hodgkin lymphoma Diseases 0.000 description 3
• 208000010747 Hodgkins lymphoma Diseases 0.000 description 3
• 241000282412 Homo Species 0.000 description 3
• 101000907904 Homo sapiens Endoribonuclease Dicer Proteins 0.000 description 3
• 101001055145 Homo sapiens Interleukin-2 receptor subunit beta Proteins 0.000 description 3
• GRRNUXAQVGOGFE-UHFFFAOYSA-N Hygromycin-B Natural products OC1C(NC)CC(N)C(O)C1OC1C2OC3(C(C(O)C(O)C(C(N)CO)O3)O)OC2C(O)C(CO)O1 GRRNUXAQVGOGFE-UHFFFAOYSA-N 0.000 description 3
• 108010091358 Hypoxanthine Phosphoribosyltransferase Proteins 0.000 description 3
• 102000018251 Hypoxanthine Phosphoribosyltransferase Human genes 0.000 description 3
• 102100026879 Interleukin-2 receptor subunit beta Human genes 0.000 description 3
• 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 3
• 206010025323 Lymphomas Diseases 0.000 description 3
• 239000004472 Lysine Substances 0.000 description 3
• 208000025205 Mantle-Cell Lymphoma Diseases 0.000 description 3
• 241000713869 Moloney murine leukemia virus Species 0.000 description 3
• 102000015636 Oligopeptides Human genes 0.000 description 3
• 108010038807 Oligopeptides Proteins 0.000 description 3
• 102100037935 Polyubiquitin-C Human genes 0.000 description 3
• ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 3
• 108091034057 RNA (poly(A)) Proteins 0.000 description 3
• 206010039491 Sarcoma Diseases 0.000 description 3
• 230000005867 T cell response Effects 0.000 description 3
• 108010022394 Threonine synthase Proteins 0.000 description 3
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 3
• 241000700647 Variola virus Species 0.000 description 3
• 108010003533 Viral Envelope Proteins Proteins 0.000 description 3
• 239000002253 acid Substances 0.000 description 3
• 210000004436 artificial bacterial chromosome Anatomy 0.000 description 3
• 229940009098 aspartate Drugs 0.000 description 3
• 239000011324 bead Substances 0.000 description 3
• 210000001185 bone marrow Anatomy 0.000 description 3
• 210000000234 capsid Anatomy 0.000 description 3
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
• 210000000170 cell membrane Anatomy 0.000 description 3
• 238000010276 construction Methods 0.000 description 3
• 230000009089 cytolysis Effects 0.000 description 3
• 231100000433 cytotoxic Toxicity 0.000 description 3
• 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 3
• 201000010099 disease Diseases 0.000 description 3
• 208000035475 disorder Diseases 0.000 description 3
• 229940079593 drug Drugs 0.000 description 3
• 241001493065 dsRNA viruses Species 0.000 description 3
• 230000009977 dual effect Effects 0.000 description 3
• 210000003162 effector t lymphocyte Anatomy 0.000 description 3
• 238000005516 engineering process Methods 0.000 description 3
• 210000004700 fetal blood Anatomy 0.000 description 3
• IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 description 3
• 229960002963 ganciclovir Drugs 0.000 description 3
• 238000001415 gene therapy Methods 0.000 description 3
• 229930195712 glutamate Natural products 0.000 description 3
• 230000004727 humoral immunity Effects 0.000 description 3
• GRRNUXAQVGOGFE-NZSRVPFOSA-N hygromycin B Chemical compound O[C@@H]1[C@@H](NC)C[C@@H](N)[C@H](O)[C@H]1O[C@H]1[C@H]2O[C@@]3([C@@H]([C@@H](O)[C@@H](O)[C@@H](C(N)CO)O3)O)O[C@H]2[C@@H](O)[C@@H](CO)O1 GRRNUXAQVGOGFE-NZSRVPFOSA-N 0.000 description 3
• 229940097277 hygromycin b Drugs 0.000 description 3
• 210000002865 immune cell Anatomy 0.000 description 3
• 230000001900 immune effect Effects 0.000 description 3
• 230000002757 inflammatory effect Effects 0.000 description 3
• 238000002955 isolation Methods 0.000 description 3
• 229960000310 isoleucine Drugs 0.000 description 3
• AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 3
• 230000000670 limiting effect Effects 0.000 description 3
• 210000001165 lymph node Anatomy 0.000 description 3
• 238000012423 maintenance Methods 0.000 description 3
• 238000010369 molecular cloning Methods 0.000 description 3
• 150000003833 nucleoside derivatives Chemical class 0.000 description 3
• 125000003835 nucleoside group Chemical group 0.000 description 3
• 230000002688 persistence Effects 0.000 description 3
• 150000003916 phosphatidylinositol 3,4,5-trisphosphates Chemical class 0.000 description 3
• 210000004180 plasmocyte Anatomy 0.000 description 3
• 230000000644 propagated effect Effects 0.000 description 3
• 230000004044 response Effects 0.000 description 3
• 238000012552 review Methods 0.000 description 3
• 102220036548 rs140382474 Human genes 0.000 description 3
• 230000035945 sensitivity Effects 0.000 description 3
• 230000019491 signal transduction Effects 0.000 description 3
• 150000003384 small molecules Chemical class 0.000 description 3
• 210000000952 spleen Anatomy 0.000 description 3
• 210000000130 stem cell Anatomy 0.000 description 3
• 201000000596 systemic lupus erythematosus Diseases 0.000 description 3
• 238000002560 therapeutic procedure Methods 0.000 description 3
• 230000002103 transcriptional effect Effects 0.000 description 3
• 241000701161 unidentified adenovirus Species 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
• 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 description 2
• 102100022900 Actin, cytoplasmic 1 Human genes 0.000 description 2
• 108010085238 Actins Proteins 0.000 description 2
• 102100036664 Adenosine deaminase Human genes 0.000 description 2
• 102000055025 Adenosine deaminases Human genes 0.000 description 2
• 241000724328 Alfalfa mosaic virus Species 0.000 description 2
• 206010003445 Ascites Diseases 0.000 description 2
• 241000714230 Avian leukemia virus Species 0.000 description 2
• 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 2
• 241000212384 Bifora Species 0.000 description 2
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
• 241000282836 Camelus dromedarius Species 0.000 description 2
• 239000004215 Carbon black (E152) Substances 0.000 description 2
• 102100026550 Caspase-9 Human genes 0.000 description 2
• 108090000566 Caspase-9 Proteins 0.000 description 2
• 108091062157 Cis-regulatory element Proteins 0.000 description 2
• 108091033380 Coding strand Proteins 0.000 description 2
• 108091035707 Consensus sequence Proteins 0.000 description 2
• 241000711573 Coronaviridae Species 0.000 description 2
• 206010050685 Cytokine storm Diseases 0.000 description 2
• 206010014611 Encephalitis venezuelan equine Diseases 0.000 description 2
• 241000283073 Equus caballus Species 0.000 description 2
• 102100039950 Eukaryotic initiation factor 4A-I Human genes 0.000 description 2
• 102100022466 Eukaryotic translation initiation factor 4E-binding protein 1 Human genes 0.000 description 2
• 108050000946 Eukaryotic translation initiation factor 4E-binding protein 1 Proteins 0.000 description 2
• 101710099785 Ferritin, heavy subunit Proteins 0.000 description 2
• 241000710781 Flaviviridae Species 0.000 description 2
• 241000714475 Fujinami sarcoma virus Species 0.000 description 2
• 101000834253 Gallus gallus Actin, cytoplasmic 1 Proteins 0.000 description 2
• 206010064571 Gene mutation Diseases 0.000 description 2
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
• BCCRXDTUTZHDEU-VKHMYHEASA-N Gly-Ser Chemical compound NCC(=O)N[C@@H](CO)C(O)=O BCCRXDTUTZHDEU-VKHMYHEASA-N 0.000 description 2
• 108010009202 Growth Factor Receptors Proteins 0.000 description 2
• 102000009465 Growth Factor Receptors Human genes 0.000 description 2
• 101000690301 Homo sapiens Aldo-keto reductase family 1 member C4 Proteins 0.000 description 2
• 101000959666 Homo sapiens Eukaryotic initiation factor 4A-I Proteins 0.000 description 2
• 101001116548 Homo sapiens Protein CBFA2T1 Proteins 0.000 description 2
• 101000638251 Homo sapiens Tumor necrosis factor ligand superfamily member 9 Proteins 0.000 description 2
• 241000701085 Human alphaherpesvirus 3 Species 0.000 description 2
• 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 2
• 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 2
• 102100034353 Integrase Human genes 0.000 description 2
• 208000007766 Kaposi sarcoma Diseases 0.000 description 2
• 102000046985 LST8 Homolog mTOR Associated Human genes 0.000 description 2
• CZQHHVNHHHRRDU-UHFFFAOYSA-N LY294002 Chemical compound C1=CC=C2C(=O)C=C(N3CCOCC3)OC2=C1C1=CC=CC=C1 CZQHHVNHHHRRDU-UHFFFAOYSA-N 0.000 description 2
• 206010023927 Lassa fever Diseases 0.000 description 2
• 101001022947 Lithobates catesbeianus Ferritin, lower subunit Proteins 0.000 description 2
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
• 108700018351 Major Histocompatibility Complex Proteins 0.000 description 2
• 241000713821 Mason-Pfizer monkey virus Species 0.000 description 2
• 108010052285 Membrane Proteins Proteins 0.000 description 2
• 241000714177 Murine leukemia virus Species 0.000 description 2
• 241000713883 Myeloproliferative sarcoma virus Species 0.000 description 2
• 244000061176 Nicotiana tabacum Species 0.000 description 2
• 235000002637 Nicotiana tabacum Nutrition 0.000 description 2
• TUVCWJQQGGETHL-UHFFFAOYSA-N PI-103 Chemical compound OC1=CC=CC(C=2N=C3C4=CC=CN=C4OC3=C(N3CCOCC3)N=2)=C1 TUVCWJQQGGETHL-UHFFFAOYSA-N 0.000 description 2
• 241001631646 Papillomaviridae Species 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 241000709664 Picornaviridae Species 0.000 description 2
• 208000007452 Plasmacytoma Diseases 0.000 description 2
• 208000002151 Pleural effusion Diseases 0.000 description 2
• 239000002202 Polyethylene glycol Substances 0.000 description 2
• 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 2
• 241000288906 Primates Species 0.000 description 2
• 102000009572 RNA Polymerase II Human genes 0.000 description 2
• 108010009460 RNA Polymerase II Proteins 0.000 description 2
• 239000012980 RPMI-1640 medium Substances 0.000 description 2
• 241000711798 Rabies lyssavirus Species 0.000 description 2
• 101001117144 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) [Pyruvate dehydrogenase (acetyl-transferring)] kinase 1, mitochondrial Proteins 0.000 description 2
• 241000555745 Sciuridae Species 0.000 description 2
• 241000710961 Semliki Forest virus Species 0.000 description 2
• 108091081021 Sense strand Proteins 0.000 description 2
• 241000150288 Sin Nombre orthohantavirus Species 0.000 description 2
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
• 241000713820 Squirrel monkey retrovirus Species 0.000 description 2
• 101710115678 Target of rapamycin complex subunit LST8 Proteins 0.000 description 2
• 108091036066 Three prime untranslated region Proteins 0.000 description 2
• 241001223089 Tremovirus A Species 0.000 description 2
• 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
• 102100036922 Tumor necrosis factor ligand superfamily member 13B Human genes 0.000 description 2
• 102100033726 Tumor necrosis factor receptor superfamily member 17 Human genes 0.000 description 2
• 108010056354 Ubiquitin C Proteins 0.000 description 2
• 108091023045 Untranslated Region Proteins 0.000 description 2
• ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
• 208000002687 Venezuelan Equine Encephalomyelitis Diseases 0.000 description 2
• 201000009145 Venezuelan equine encephalitis Diseases 0.000 description 2
• 108020000999 Viral RNA Proteins 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• 239000000654 additive Substances 0.000 description 2
• 239000000556 agonist Substances 0.000 description 2
• 238000004458 analytical method Methods 0.000 description 2
• 230000000259 anti-tumor effect Effects 0.000 description 2
• 230000007503 antigenic stimulation Effects 0.000 description 2
• 210000004507 artificial chromosome Anatomy 0.000 description 2
• 210000001106 artificial yeast chromosome Anatomy 0.000 description 2
• 238000003556 assay Methods 0.000 description 2
• 230000001580 bacterial effect Effects 0.000 description 2
• 230000001588 bifunctional effect Effects 0.000 description 2
• 230000008827 biological function Effects 0.000 description 2
• 210000000601 blood cell Anatomy 0.000 description 2
• 210000001772 blood platelet Anatomy 0.000 description 2
• 238000009835 boiling Methods 0.000 description 2
• GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 description 2
• 108010006025 bovine growth hormone Proteins 0.000 description 2
• 238000009395 breeding Methods 0.000 description 2
• 230000001488 breeding effect Effects 0.000 description 2
• 229910052791 calcium Inorganic materials 0.000 description 2
• 239000011575 calcium Substances 0.000 description 2
• 150000001768 cations Chemical class 0.000 description 2
• 238000004113 cell culture Methods 0.000 description 2
• 230000005779 cell damage Effects 0.000 description 2
• 230000024245 cell differentiation Effects 0.000 description 2
• 230000010261 cell growth Effects 0.000 description 2
• 208000037887 cell injury Diseases 0.000 description 2
• 210000003850 cellular structure Anatomy 0.000 description 2
• 238000005119 centrifugation Methods 0.000 description 2
• 238000006243 chemical reaction Methods 0.000 description 2
• 239000003153 chemical reaction reagent Substances 0.000 description 2
• 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 2
• 238000004590 computer program Methods 0.000 description 2
• 239000000562 conjugate Substances 0.000 description 2
• 238000004132 cross linking Methods 0.000 description 2
• 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
• 150000001945 cysteines Chemical class 0.000 description 2
• 206010052015 cytokine release syndrome Diseases 0.000 description 2
• 230000001461 cytolytic effect Effects 0.000 description 2
• 230000003013 cytotoxicity Effects 0.000 description 2
• 231100000135 cytotoxicity Toxicity 0.000 description 2
• 229950006418 dactolisib Drugs 0.000 description 2
• JOGKUKXHTYWRGZ-UHFFFAOYSA-N dactolisib Chemical compound O=C1N(C)C2=CN=C3C=CC(C=4C=C5C=CC=CC5=NC=4)=CC3=C2N1C1=CC=C(C(C)(C)C#N)C=C1 JOGKUKXHTYWRGZ-UHFFFAOYSA-N 0.000 description 2
• 230000006378 damage Effects 0.000 description 2
• 238000011161 development Methods 0.000 description 2
• 230000018109 developmental process Effects 0.000 description 2
• 102000004419 dihydrofolate reductase Human genes 0.000 description 2
• 239000000539 dimer Substances 0.000 description 2
• 238000004520 electroporation Methods 0.000 description 2
• 230000008030 elimination Effects 0.000 description 2
• 238000003379 elimination reaction Methods 0.000 description 2
• 108010078428 env Gene Products Proteins 0.000 description 2
• 108700004025 env Genes Proteins 0.000 description 2
• 230000001747 exhibiting effect Effects 0.000 description 2
• 108700014844 flt3 ligand Proteins 0.000 description 2
• 238000010353 genetic engineering Methods 0.000 description 2
• 102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 2
• 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 2
• 235000011187 glycerol Nutrition 0.000 description 2
• 210000003714 granulocyte Anatomy 0.000 description 2
• 208000006454 hepatitis Diseases 0.000 description 2
• 231100000283 hepatitis Toxicity 0.000 description 2
• 229940088597 hormone Drugs 0.000 description 2
• 239000005556 hormone Substances 0.000 description 2
• 102000054751 human RUNX1T1 Human genes 0.000 description 2
• 210000005260 human cell Anatomy 0.000 description 2
• 238000009396 hybridization Methods 0.000 description 2
• 210000004408 hybridoma Anatomy 0.000 description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
• 230000000977 initiatory effect Effects 0.000 description 2
• NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
• 230000005732 intercellular adhesion Effects 0.000 description 2
• 230000002427 irreversible effect Effects 0.000 description 2
• 231100000518 lethal Toxicity 0.000 description 2
• 230000001665 lethal effect Effects 0.000 description 2
• 210000000265 leukocyte Anatomy 0.000 description 2
• 210000002540 macrophage Anatomy 0.000 description 2
• 229910052749 magnesium Inorganic materials 0.000 description 2
• 239000011777 magnesium Substances 0.000 description 2
• 230000003211 malignant effect Effects 0.000 description 2
• 239000000463 material Substances 0.000 description 2
• 238000003032 molecular docking Methods 0.000 description 2
• 238000010172 mouse model Methods 0.000 description 2
• 230000036457 multidrug resistance Effects 0.000 description 2
• 206010028417 myasthenia gravis Diseases 0.000 description 2
• 239000013642 negative control Substances 0.000 description 2
• 210000000440 neutrophil Anatomy 0.000 description 2
• 210000005259 peripheral blood Anatomy 0.000 description 2
• 239000011886 peripheral blood Substances 0.000 description 2
• 239000002953 phosphate buffered saline Substances 0.000 description 2
• 229920001223 polyethylene glycol Polymers 0.000 description 2
• 229920006316 polyvinylpyrrolidine Polymers 0.000 description 2
• 230000004481 post-translational protein modification Effects 0.000 description 2
• 238000001556 precipitation Methods 0.000 description 2
• 239000002243 precursor Substances 0.000 description 2
• 238000004321 preservation Methods 0.000 description 2
• 230000002062 proliferating effect Effects 0.000 description 2
• 230000001902 propagating effect Effects 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
• 230000002829 reductive effect Effects 0.000 description 2
• 230000003362 replicative effect Effects 0.000 description 2
• 108091008146 restriction endonucleases Proteins 0.000 description 2
• 206010039073 rheumatoid arthritis Diseases 0.000 description 2
• 102220128858 rs200860772 Human genes 0.000 description 2
• 102220288357 rs572035776 Human genes 0.000 description 2
• 102220146256 rs886059153 Human genes 0.000 description 2
• 238000012216 screening Methods 0.000 description 2
• 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 2
• 239000002924 silencing RNA Substances 0.000 description 2
• QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 2
• 239000002904 solvent Substances 0.000 description 2
• 230000010473 stable expression Effects 0.000 description 2
• 239000011550 stock solution Substances 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
• 238000007920 subcutaneous administration Methods 0.000 description 2
• 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 2
• 208000011580 syndromic disease Diseases 0.000 description 2
• RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
• 210000001541 thymus gland Anatomy 0.000 description 2
• 230000005030 transcription termination Effects 0.000 description 2
• 230000032258 transport Effects 0.000 description 2
• 210000004881 tumor cell Anatomy 0.000 description 2
• 238000011144 upstream manufacturing Methods 0.000 description 2
• 210000002845 virion Anatomy 0.000 description 2
• 238000010792 warming Methods 0.000 description 2
• DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
• DIGQNXIGRZPYDK-WKSCXVIASA-N (2R)-6-amino-2-[[2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-[[(2R,3S)-2-[[2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S,3S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2R)-2-[[2-[[2-[[2-[(2-amino-1-hydroxyethylidene)amino]-3-carboxy-1-hydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1,5-dihydroxy-5-iminopentylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]hexanoic acid Chemical compound C[C@@H]([C@@H](C(=N[C@@H](CS)C(=N[C@@H](C)C(=N[C@@H](CO)C(=NCC(=N[C@@H](CCC(=N)O)C(=NC(CS)C(=N[C@H]([C@H](C)O)C(=N[C@H](CS)C(=N[C@H](CO)C(=NCC(=N[C@H](CS)C(=NCC(=N[C@H](CCCCN)C(=O)O)O)O)O)O)O)O)O)O)O)O)O)O)O)N=C([C@H](CS)N=C([C@H](CO)N=C([C@H](CO)N=C([C@H](C)N=C(CN=C([C@H](CO)N=C([C@H](CS)N=C(CN=C(C(CS)N=C(C(CC(=O)O)N=C(CN)O)O)O)O)O)O)O)O)O)O)O)O DIGQNXIGRZPYDK-WKSCXVIASA-N 0.000 description 1
• GRZXWCHAXNAUHY-NSISKUIASA-N (2S)-2-(4-chlorophenyl)-1-[4-[(5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl]-1-piperazinyl]-3-(propan-2-ylamino)-1-propanone Chemical compound C1([C@H](C(=O)N2CCN(CC2)C=2C=3[C@H](C)C[C@@H](O)C=3N=CN=2)CNC(C)C)=CC=C(Cl)C=C1 GRZXWCHAXNAUHY-NSISKUIASA-N 0.000 description 1
• STUWGJZDJHPWGZ-LBPRGKRZSA-N (2S)-N1-[4-methyl-5-[2-(1,1,1-trifluoro-2-methylpropan-2-yl)-4-pyridinyl]-2-thiazolyl]pyrrolidine-1,2-dicarboxamide Chemical compound S1C(C=2C=C(N=CC=2)C(C)(C)C(F)(F)F)=C(C)N=C1NC(=O)N1CCC[C@H]1C(N)=O STUWGJZDJHPWGZ-LBPRGKRZSA-N 0.000 description 1
• VKYBWTVHQHFSJL-ZATYTLRZSA-N (2s)-2,5-diamino-5-oxopentanoic acid;(2s)-pyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1.OC(=O)[C@@H](N)CCC(N)=O VKYBWTVHQHFSJL-ZATYTLRZSA-N 0.000 description 1
• KUHSEZKIEJYEHN-BXRBKJIMSA-N (2s)-2-amino-3-hydroxypropanoic acid;(2s)-2-aminopropanoic acid Chemical compound C[C@H](N)C(O)=O.OC[C@H](N)C(O)=O KUHSEZKIEJYEHN-BXRBKJIMSA-N 0.000 description 1
• NMNYMRMXUPRAKF-TYHJCQIPSA-N (2s,3s)-2-amino-3-methylpentanoic acid;(2s)-2,6-diaminohexanoic acid Chemical compound CC[C@H](C)[C@H](N)C(O)=O.NCCCC[C@H](N)C(O)=O NMNYMRMXUPRAKF-TYHJCQIPSA-N 0.000 description 1
• MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
• QDITZBLZQQZVEE-YBEGLDIGSA-N (5z)-5-[(4-pyridin-4-ylquinolin-6-yl)methylidene]-1,3-thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)\C1=C\C1=CC=C(N=CC=C2C=3C=CN=CC=3)C2=C1 QDITZBLZQQZVEE-YBEGLDIGSA-N 0.000 description 1
• 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
• 108091064702 1 family Proteins 0.000 description 1
• APXRHPDHORGIEB-UHFFFAOYSA-N 1H-pyrazolo[4,3-d]pyrimidine Chemical class N1=CN=C2C=NNC2=C1 APXRHPDHORGIEB-UHFFFAOYSA-N 0.000 description 1
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
• XTKLTGBKIDQGQL-UHFFFAOYSA-N 2-methyl-1-[[2-methyl-3-(trifluoromethyl)phenyl]methyl]-6-morpholin-4-ylbenzimidazole-4-carboxylic acid Chemical compound CC1=NC2=C(C(O)=O)C=C(N3CCOCC3)C=C2N1CC1=CC=CC(C(F)(F)F)=C1C XTKLTGBKIDQGQL-UHFFFAOYSA-N 0.000 description 1
• UOORQSPLBHUQDQ-UHFFFAOYSA-N 3-(2,4-diaminopteridin-6-yl)phenol Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1C1=CC=CC(O)=C1 UOORQSPLBHUQDQ-UHFFFAOYSA-N 0.000 description 1
• RHKWIGHJGOEUSM-UHFFFAOYSA-N 3h-imidazo[4,5-h]quinoline Chemical class C1=CN=C2C(N=CN3)=C3C=CC2=C1 RHKWIGHJGOEUSM-UHFFFAOYSA-N 0.000 description 1
• ZLHLYESIHSHXGM-UHFFFAOYSA-N 4,6-dimethyl-1h-imidazo[1,2-a]purin-9-one Chemical compound N=1C(C)=CN(C2=O)C=1N(C)C1=C2NC=N1 ZLHLYESIHSHXGM-UHFFFAOYSA-N 0.000 description 1
• RZIDZIGAXXNODG-UHFFFAOYSA-N 4-[(4-chlorophenyl)methyl]-1-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-amine Chemical group C1CN(C=2C=3C=CNC=3N=CN=2)CCC1(N)CC1=CC=C(Cl)C=C1 RZIDZIGAXXNODG-UHFFFAOYSA-N 0.000 description 1
• FPEIJQLXFHKLJV-UHFFFAOYSA-N 4-[6-(1h-indol-5-yl)-1-[1-(pyridin-3-ylmethyl)piperidin-4-yl]pyrazolo[3,4-d]pyrimidin-4-yl]morpholine Chemical compound C=1C=CN=CC=1CN(CC1)CCC1N(C1=NC(=N2)C=3C=C4C=CNC4=CC=3)N=CC1=C2N1CCOCC1 FPEIJQLXFHKLJV-UHFFFAOYSA-N 0.000 description 1
• SJVQHLPISAIATJ-ZDUSSCGKSA-N 8-chloro-2-phenyl-3-[(1S)-1-(7H-purin-6-ylamino)ethyl]-1-isoquinolinone Chemical compound C1([C@@H](NC=2C=3N=CNC=3N=CN=2)C)=CC2=CC=CC(Cl)=C2C(=O)N1C1=CC=CC=C1 SJVQHLPISAIATJ-ZDUSSCGKSA-N 0.000 description 1
• CPRAGQJXBLMUEL-UHFFFAOYSA-N 9-(1-anilinoethyl)-7-methyl-2-(4-morpholinyl)-4-pyrido[1,2-a]pyrimidinone Chemical compound C=1C(C)=CN(C(C=C(N=2)N3CCOCC3)=O)C=2C=1C(C)NC1=CC=CC=C1 CPRAGQJXBLMUEL-UHFFFAOYSA-N 0.000 description 1
• 101150107888 AKT2 gene Proteins 0.000 description 1
• KVLFRAWTRWDEDF-IRXDYDNUSA-N AZD-8055 Chemical compound C1=C(CO)C(OC)=CC=C1C1=CC=C(C(=NC(=N2)N3[C@H](COCC3)C)N3[C@H](COCC3)C)C2=N1 KVLFRAWTRWDEDF-IRXDYDNUSA-N 0.000 description 1
• 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
• 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
• 241000701242 Adenoviridae Species 0.000 description 1
• 230000007730 Akt signaling Effects 0.000 description 1
• QNAYBMKLOCPYGJ-UHFFFAOYSA-N Alanine Chemical compound CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 1
• 241000710929 Alphavirus Species 0.000 description 1
• 208000003829 American Hemorrhagic Fever Diseases 0.000 description 1
• 206010001935 American trypanosomiasis Diseases 0.000 description 1
• 208000002267 Anti-neutrophil cytoplasmic antibody-associated vasculitis Diseases 0.000 description 1
• 101710145634 Antigen 1 Proteins 0.000 description 1
• 208000003343 Antiphospholipid Syndrome Diseases 0.000 description 1
• 241000712891 Arenavirus Species 0.000 description 1
• 241001533362 Astroviridae Species 0.000 description 1
• 102100039339 Atrial natriuretic peptide receptor 1 Human genes 0.000 description 1
• 101710102163 Atrial natriuretic peptide receptor 1 Proteins 0.000 description 1
• 102100029822 B- and T-lymphocyte attenuator Human genes 0.000 description 1
• 108010028006 B-Cell Activating Factor Proteins 0.000 description 1
• 208000037914 B-cell disorder Diseases 0.000 description 1
• 206010003908 B-cell small lymphocytic lymphoma Diseases 0.000 description 1
• 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 1
• YUXMAKUNSXIEKN-BTJKTKAUSA-N BGT226 Chemical compound OC(=O)\C=C/C(O)=O.C1=NC(OC)=CC=C1C1=CC=C(N=CC2=C3N(C=4C=C(C(N5CCNCC5)=CC=4)C(F)(F)F)C(=O)N2C)C3=C1 YUXMAKUNSXIEKN-BTJKTKAUSA-N 0.000 description 1
• CWHUFRVAEUJCEF-UHFFFAOYSA-N BKM120 Chemical compound C1=NC(N)=CC(C(F)(F)F)=C1C1=CC(N2CCOCC2)=NC(N2CCOCC2)=N1 CWHUFRVAEUJCEF-UHFFFAOYSA-N 0.000 description 1
• 241000894006 Bacteria Species 0.000 description 1
• 102220638993 Beta-enolase_H16C_mutation Human genes 0.000 description 1
• 208000034200 Bolivian hemorrhagic fever Diseases 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• 241000167854 Bourreria succulenta Species 0.000 description 1
• 241000701822 Bovine papillomavirus Species 0.000 description 1
• 206010006187 Breast cancer Diseases 0.000 description 1
• 208000026310 Breast neoplasm Diseases 0.000 description 1
• 125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
• 238000011357 CAR T-cell therapy Methods 0.000 description 1
• 102100038078 CD276 antigen Human genes 0.000 description 1
• 102100025221 CD70 antigen Human genes 0.000 description 1
• 101001125868 Caenorhabditis elegans Phosphatidylinositol 3-kinase piki-1 Proteins 0.000 description 1
• 108090000397 Caspase 3 Proteins 0.000 description 1
• 102100029855 Caspase-3 Human genes 0.000 description 1
• 102100026548 Caspase-8 Human genes 0.000 description 1
• 108090000538 Caspase-8 Proteins 0.000 description 1
• 208000024699 Chagas disease Diseases 0.000 description 1
• 241000251730 Chondrichthyes Species 0.000 description 1
• 241001533399 Circoviridae Species 0.000 description 1
• 108010051219 Cre recombinase Proteins 0.000 description 1
• 241000150230 Crimean-Congo hemorrhagic fever orthonairovirus Species 0.000 description 1
• 241000195493 Cryptophyta Species 0.000 description 1
• 102000053602 DNA Human genes 0.000 description 1
• 101710177611 DNA polymerase II large subunit Proteins 0.000 description 1
• 101710184669 DNA polymerase II small subunit Proteins 0.000 description 1
• 241000450599 DNA viruses Species 0.000 description 1
• 230000004568 DNA-binding Effects 0.000 description 1
• 208000001490 Dengue Diseases 0.000 description 1
• 206010012310 Dengue fever Diseases 0.000 description 1
• 241000702421 Dependoparvovirus Species 0.000 description 1
• 241000712471 Dhori virus Species 0.000 description 1
• 101001031598 Dictyostelium discoideum Probable serine/threonine-protein kinase fhkC Proteins 0.000 description 1
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
• 241001520695 Duvenhage lyssavirus Species 0.000 description 1
• 241000710945 Eastern equine encephalitis virus Species 0.000 description 1
• 201000011001 Ebola Hemorrhagic Fever Diseases 0.000 description 1
• 208000030820 Ebola disease Diseases 0.000 description 1
• 241001115402 Ebolavirus Species 0.000 description 1
• 101710088791 Elongation factor 2 Proteins 0.000 description 1
• 102100039328 Endoplasmin Human genes 0.000 description 1
• 102100023387 Endoribonuclease Dicer Human genes 0.000 description 1
• 102100029727 Enteropeptidase Human genes 0.000 description 1
• 108010013369 Enteropeptidase Proteins 0.000 description 1
• 101710121417 Envelope glycoprotein Proteins 0.000 description 1
• 241001455610 Ephemerovirus Species 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
• 101001091269 Escherichia coli Hygromycin-B 4-O-kinase Proteins 0.000 description 1
• 241000701959 Escherichia virus Lambda Species 0.000 description 1
• 241001524679 Escherichia virus M13 Species 0.000 description 1
• 108060002716 Exonuclease Proteins 0.000 description 1
• 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
• 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
• 108010087819 Fc receptors Proteins 0.000 description 1
• 102000009109 Fc receptors Human genes 0.000 description 1
• 241000710198 Foot-and-mouth disease virus Species 0.000 description 1
• 241000712469 Fowl plague virus Species 0.000 description 1
• 241000233866 Fungi Species 0.000 description 1
• 108700042658 GAP-43 Proteins 0.000 description 1
• KGPGFQWBCSZGEL-ZDUSSCGKSA-N GSK690693 Chemical compound C=12N(CC)C(C=3C(=NON=3)N)=NC2=C(C#CC(C)(C)O)N=CC=1OC[C@H]1CCCNC1 KGPGFQWBCSZGEL-ZDUSSCGKSA-N 0.000 description 1
• 241000701047 Gallid alphaherpesvirus 2 Species 0.000 description 1
• 241000287828 Gallus gallus Species 0.000 description 1
• 101001035782 Gallus gallus Hemoglobin subunit beta Proteins 0.000 description 1
• 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
• 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
• 241000713813 Gibbon ape leukemia virus Species 0.000 description 1
• YRMZCZIRHYCNHX-RYUDHWBXSA-N Glu-Phe-Gly Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)NCC(O)=O YRMZCZIRHYCNHX-RYUDHWBXSA-N 0.000 description 1
• 102000003676 Glucocorticoid Receptors Human genes 0.000 description 1
• 108090000079 Glucocorticoid Receptors Proteins 0.000 description 1
• 102000003886 Glycoproteins Human genes 0.000 description 1
• 108090000288 Glycoproteins Proteins 0.000 description 1
• 208000024869 Goodpasture syndrome Diseases 0.000 description 1
• 108010092372 Granulocyte-Macrophage Colony-Stimulating Factor Receptors Proteins 0.000 description 1
• 102000016355 Granulocyte-Macrophage Colony-Stimulating Factor Receptors Human genes 0.000 description 1
• 206010072579 Granulomatosis with polyangiitis Diseases 0.000 description 1
• 208000003807 Graves Disease Diseases 0.000 description 1
• 208000015023 Graves' disease Diseases 0.000 description 1
• 239000007995 HEPES buffer Substances 0.000 description 1
• 102100028967 HLA class I histocompatibility antigen, alpha chain G Human genes 0.000 description 1
• 108010024164 HLA-G Antigens Proteins 0.000 description 1
• 102000018932 HSP70 Heat-Shock Proteins Human genes 0.000 description 1
• 108010027992 HSP70 Heat-Shock Proteins Proteins 0.000 description 1
• 101100356020 Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd) recA gene Proteins 0.000 description 1
• 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 description 1
• 241000893570 Hendra henipavirus Species 0.000 description 1
• 241000711549 Hepacivirus C Species 0.000 description 1
• 241000700739 Hepadnaviridae Species 0.000 description 1
• 241000724675 Hepatitis E virus Species 0.000 description 1
• 208000037262 Hepatitis delta Diseases 0.000 description 1
• 241000724709 Hepatitis delta virus Species 0.000 description 1
• 206010019799 Hepatitis viral Diseases 0.000 description 1
• 241000700586 Herpesviridae Species 0.000 description 1
• 101000864344 Homo sapiens B- and T-lymphocyte attenuator Proteins 0.000 description 1
• 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 1
• 101000934356 Homo sapiens CD70 antigen Proteins 0.000 description 1
• 101000812663 Homo sapiens Endoplasmin Proteins 0.000 description 1
• 101000998953 Homo sapiens Immunoglobulin heavy variable 1-2 Proteins 0.000 description 1
• 101001008255 Homo sapiens Immunoglobulin kappa variable 1D-8 Proteins 0.000 description 1
• 101001047628 Homo sapiens Immunoglobulin kappa variable 2-29 Proteins 0.000 description 1
• 101001008321 Homo sapiens Immunoglobulin kappa variable 2D-26 Proteins 0.000 description 1
• 101001047619 Homo sapiens Immunoglobulin kappa variable 3-20 Proteins 0.000 description 1
• 101001008263 Homo sapiens Immunoglobulin kappa variable 3D-15 Proteins 0.000 description 1
• 101001046686 Homo sapiens Integrin alpha-M Proteins 0.000 description 1
• 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 1
• 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 1
• 101000984189 Homo sapiens Leukocyte immunoglobulin-like receptor subfamily B member 2 Proteins 0.000 description 1
• 101000984186 Homo sapiens Leukocyte immunoglobulin-like receptor subfamily B member 4 Proteins 0.000 description 1
• 101000991061 Homo sapiens MHC class I polypeptide-related sequence B Proteins 0.000 description 1
• 101001057156 Homo sapiens Melanoma-associated antigen C2 Proteins 0.000 description 1
• 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 1
• 101001109503 Homo sapiens NKG2-C type II integral membrane protein Proteins 0.000 description 1
• 101000622137 Homo sapiens P-selectin Proteins 0.000 description 1
• 101000690268 Homo sapiens Proline-rich AKT1 substrate 1 Proteins 0.000 description 1
• 101000600434 Homo sapiens Putative uncharacterized protein encoded by MIR7-3HG Proteins 0.000 description 1
• 101000779418 Homo sapiens RAC-alpha serine/threonine-protein kinase Proteins 0.000 description 1
• 101000798015 Homo sapiens RAC-beta serine/threonine-protein kinase Proteins 0.000 description 1
• 101000798007 Homo sapiens RAC-gamma serine/threonine-protein kinase Proteins 0.000 description 1
• 101100207070 Homo sapiens TNFSF8 gene Proteins 0.000 description 1
• 101000652747 Homo sapiens Target of rapamycin complex 2 subunit MAPKAP1 Proteins 0.000 description 1
• 108700020129 Human immunodeficiency virus 1 p31 integrase Proteins 0.000 description 1
• 206010021245 Idiopathic thrombocytopenic purpura Diseases 0.000 description 1
• 108700002232 Immediate-Early Genes Proteins 0.000 description 1
• 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 1
• 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 1
• 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 1
• 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 1
• 102100036887 Immunoglobulin heavy variable 1-2 Human genes 0.000 description 1
• 102100022964 Immunoglobulin kappa variable 3-20 Human genes 0.000 description 1
• 241000712431 Influenza A virus Species 0.000 description 1
• 241000713297 Influenza C virus Species 0.000 description 1
• 208000002979 Influenza in Birds Diseases 0.000 description 1
• 108090001061 Insulin Proteins 0.000 description 1
• 102000004877 Insulin Human genes 0.000 description 1
• 102000003746 Insulin Receptor Human genes 0.000 description 1
• 108010001127 Insulin Receptor Proteins 0.000 description 1
• 102100022338 Integrin alpha-M Human genes 0.000 description 1
• 102100027268 Interferon-stimulated gene 20 kDa protein Human genes 0.000 description 1
• 108010050904 Interferons Proteins 0.000 description 1
• 102000014150 Interferons Human genes 0.000 description 1
• 108010065805 Interleukin-12 Proteins 0.000 description 1
• 102000013462 Interleukin-12 Human genes 0.000 description 1
• 102100030703 Interleukin-22 Human genes 0.000 description 1
• 102000000646 Interleukin-3 Human genes 0.000 description 1
• 108010002386 Interleukin-3 Proteins 0.000 description 1
• 102000004388 Interleukin-4 Human genes 0.000 description 1
• 108090000978 Interleukin-4 Proteins 0.000 description 1
• 108090001005 Interleukin-6 Proteins 0.000 description 1
• 102000004889 Interleukin-6 Human genes 0.000 description 1
• 108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 1
• 108091092195 Intron Proteins 0.000 description 1
• 241000701377 Iridoviridae Species 0.000 description 1
• 108020003285 Isocitrate lyase Proteins 0.000 description 1
• 108010025815 Kanamycin Kinase Proteins 0.000 description 1
• 208000011200 Kawasaki disease Diseases 0.000 description 1
• 241001466978 Kyasanur forest disease virus Species 0.000 description 1
• PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 1
• ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
• 125000000998 L-alanino group Chemical group [H]N([*])[C@](C([H])([H])[H])([H])C(=O)O[H] 0.000 description 1
• ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
• ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
• 125000000393 L-methionino group Chemical group [H]OC(=O)[C@@]([H])(N([H])[*])C([H])([H])C(SC([H])([H])[H])([H])[H] 0.000 description 1
• 125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 description 1
• 125000000510 L-tryptophano group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C(C([H])([H])[C@@]([H])(C(O[H])=O)N([H])[*])C2=C1[H] 0.000 description 1
• 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 description 1
• 108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
• 102100025583 Leukocyte immunoglobulin-like receptor subfamily B member 2 Human genes 0.000 description 1
• 102100025578 Leukocyte immunoglobulin-like receptor subfamily B member 4 Human genes 0.000 description 1
• 108010091221 Lymphotoxin beta Receptor Proteins 0.000 description 1
• 102000018170 Lymphotoxin beta Receptor Human genes 0.000 description 1
• ORVFEGYUJITPGI-IHRRRGAJSA-N Lys-Leu-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCCCN ORVFEGYUJITPGI-IHRRRGAJSA-N 0.000 description 1
• 241000711828 Lyssavirus Species 0.000 description 1
• 102100030301 MHC class I polypeptide-related sequence A Human genes 0.000 description 1
• 102100030300 MHC class I polypeptide-related sequence B Human genes 0.000 description 1
• 229940124640 MK-2206 Drugs 0.000 description 1
• 206010064912 Malignant transformation Diseases 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• 208000000932 Marburg Virus Disease Diseases 0.000 description 1
• 201000011013 Marburg hemorrhagic fever Diseases 0.000 description 1
• 102100027252 Melanoma-associated antigen C2 Human genes 0.000 description 1
• 102000012750 Membrane Glycoproteins Human genes 0.000 description 1
• 108010090054 Membrane Glycoproteins Proteins 0.000 description 1
• 102000018697 Membrane Proteins Human genes 0.000 description 1
• 102000003792 Metallothionein Human genes 0.000 description 1
• 108090000157 Metallothionein Proteins 0.000 description 1
• 102220485636 Mitogen-activated protein kinase 15_K42A_mutation Human genes 0.000 description 1
• 241000725171 Mokola lyssavirus Species 0.000 description 1
• 241000700627 Monkeypox virus Species 0.000 description 1
• 208000010190 Monoclonal Gammopathy of Undetermined Significance Diseases 0.000 description 1
• 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 1
• 241000711513 Mononegavirales Species 0.000 description 1
• 241001529936 Murinae Species 0.000 description 1
• 241001455073 Murine herpesvirus Species 0.000 description 1
• 241000711408 Murine respirovirus Species 0.000 description 1
• 101100087591 Mus musculus Rictor gene Proteins 0.000 description 1
• 101100042680 Mus musculus Slc7a1 gene Proteins 0.000 description 1
• 101100207071 Mus musculus Tnfsf8 gene Proteins 0.000 description 1
• 125000000729 N-terminal amino-acid group Chemical group 0.000 description 1
• 102100022683 NKG2-C type II integral membrane protein Human genes 0.000 description 1
• 229930193140 Neomycin Natural products 0.000 description 1
• 241000526636 Nipah henipavirus Species 0.000 description 1
• 241001263478 Norovirus Species 0.000 description 1
• 101710163270 Nuclease Proteins 0.000 description 1
• 241000725177 Omsk hemorrhagic fever virus Species 0.000 description 1
• 108700026244 Open Reading Frames Proteins 0.000 description 1
• 241000150452 Orthohantavirus Species 0.000 description 1
• 241000712464 Orthomyxoviridae Species 0.000 description 1
• 240000007594 Oryza sativa Species 0.000 description 1
• 235000007164 Oryza sativa Nutrition 0.000 description 1
• 102000004316 Oxidoreductases Human genes 0.000 description 1
• 108090000854 Oxidoreductases Proteins 0.000 description 1
• 102220497402 Oxysterol-binding protein-related protein 3_K71A_mutation Human genes 0.000 description 1
• 102100023472 P-selectin Human genes 0.000 description 1
• 206010053869 POEMS syndrome Diseases 0.000 description 1
• 108091081548 Palindromic sequence Proteins 0.000 description 1
• 108090000526 Papain Proteins 0.000 description 1
• 241000711504 Paramyxoviridae Species 0.000 description 1
• 241000701945 Parvoviridae Species 0.000 description 1
• 201000011152 Pemphigus 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
• 102000057297 Pepsin A Human genes 0.000 description 1
• 108090000284 Pepsin A Proteins 0.000 description 1
• 102000007079 Peptide Fragments Human genes 0.000 description 1
• 108010033276 Peptide Fragments Proteins 0.000 description 1
• 108010043958 Peptoids Proteins 0.000 description 1
• KHGNFPUMBJSZSM-UHFFFAOYSA-N Perforine Natural products COC1=C2CCC(O)C(CCC(C)(C)O)(OC)C2=NC2=C1C=CO2 KHGNFPUMBJSZSM-UHFFFAOYSA-N 0.000 description 1
• 206010057249 Phagocytosis Diseases 0.000 description 1
• 108091000080 Phosphotransferase Proteins 0.000 description 1
• 206010035148 Plague Diseases 0.000 description 1
• 241001505332 Polyomavirus sp. Species 0.000 description 1
• 102100024091 Proline-rich AKT1 substrate 1 Human genes 0.000 description 1
• 108090000315 Protein Kinase C Proteins 0.000 description 1
• 102000003923 Protein Kinase C Human genes 0.000 description 1
• 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 1
• 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 1
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
• 241000125945 Protoparvovirus Species 0.000 description 1
• KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 1
• 102100037401 Putative uncharacterized protein encoded by MIR7-3HG Human genes 0.000 description 1
• 101710113459 RAC-alpha serine/threonine-protein kinase Proteins 0.000 description 1
• 102100032315 RAC-beta serine/threonine-protein kinase Human genes 0.000 description 1
• 102100032314 RAC-gamma serine/threonine-protein kinase Human genes 0.000 description 1
• 230000006819 RNA synthesis Effects 0.000 description 1
• 108700019578 Ras Homolog Enriched in Brain Proteins 0.000 description 1
• 102000046951 Ras Homolog Enriched in Brain Human genes 0.000 description 1
• 101001009851 Rattus norvegicus Guanylate cyclase 2G Proteins 0.000 description 1
• 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
• 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
• 108010029031 Regulatory-Associated Protein of mTOR Proteins 0.000 description 1
• 102100040969 Regulatory-associated protein of mTOR Human genes 0.000 description 1
• 241001068295 Replication defective viruses Species 0.000 description 1
• 108091027981 Response element Proteins 0.000 description 1
• 241000711931 Rhabdoviridae Species 0.000 description 1
• 108091028664 Ribonucleotide Proteins 0.000 description 1
• 102000003861 Ribosomal protein S6 Human genes 0.000 description 1
• 108090000221 Ribosomal protein S6 Proteins 0.000 description 1
• 102100024908 Ribosomal protein S6 kinase beta-1 Human genes 0.000 description 1
• 101710108924 Ribosomal protein S6 kinase beta-1 Proteins 0.000 description 1
• 241001492231 Rice tungro spherical virus Species 0.000 description 1
• 241000713124 Rift Valley fever virus Species 0.000 description 1
• 235000011449 Rosa Nutrition 0.000 description 1
• 241000702670 Rotavirus Species 0.000 description 1
• 241000736032 Sabia <angiosperm> Species 0.000 description 1
• 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
• 241000282695 Saimiri Species 0.000 description 1
• 241000785686 Sander Species 0.000 description 1
• 206010039710 Scleroderma Diseases 0.000 description 1
• 238000012300 Sequence Analysis Methods 0.000 description 1
• 102000012010 Sialomucins Human genes 0.000 description 1
• 108010061228 Sialomucins Proteins 0.000 description 1
• 241001529934 Simian T-lymphotropic virus 3 Species 0.000 description 1
• 208000021386 Sjogren Syndrome Diseases 0.000 description 1
• 108020004688 Small Nuclear RNA Proteins 0.000 description 1
• 102000039471 Small Nuclear RNA Human genes 0.000 description 1
• 102220509593 Small integral membrane protein 10_H51A_mutation Human genes 0.000 description 1
• 241000713675 Spumavirus Species 0.000 description 1
• 108091081024 Start codon Proteins 0.000 description 1
• 101001091268 Streptomyces hygroscopicus Hygromycin-B 7''-O-kinase Proteins 0.000 description 1
• 101710172711 Structural protein Proteins 0.000 description 1
• 241000272534 Struthio camelus Species 0.000 description 1
• 230000006044 T cell activation Effects 0.000 description 1
• 101150056647 TNFRSF4 gene Proteins 0.000 description 1
• 102000018679 Tacrolimus Binding Proteins Human genes 0.000 description 1
• 108010027179 Tacrolimus Binding Proteins Proteins 0.000 description 1
• 101000588258 Taenia solium Paramyosin Proteins 0.000 description 1
• 102100030904 Target of rapamycin complex 2 subunit MAPKAP1 Human genes 0.000 description 1
• 108020005038 Terminator Codon Proteins 0.000 description 1
• 239000004098 Tetracycline Substances 0.000 description 1
• 241001648840 Thosea asigna virus Species 0.000 description 1
• 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 description 1
• 102000036693 Thrombopoietin Human genes 0.000 description 1
• 108010041111 Thrombopoietin Proteins 0.000 description 1
• 208000007536 Thrombosis Diseases 0.000 description 1
• IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical group O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 1
• 108010010574 Tn3 resolvase Proteins 0.000 description 1
• 241000710924 Togaviridae Species 0.000 description 1
• 108700009124 Transcription Initiation Site Proteins 0.000 description 1
• 108091023040 Transcription factor Proteins 0.000 description 1
• 102000040945 Transcription factor Human genes 0.000 description 1
• 101800001690 Transmembrane protein gp41 Proteins 0.000 description 1
• 241000223109 Trypanosoma cruzi Species 0.000 description 1
• 101710181056 Tumor necrosis factor ligand superfamily member 13B Proteins 0.000 description 1
• 102100032100 Tumor necrosis factor ligand superfamily member 8 Human genes 0.000 description 1
• 108091026822 U6 spliceosomal RNA Proteins 0.000 description 1
• 241000700618 Vaccinia virus Species 0.000 description 1
• 102220635504 Vacuolar protein sorting-associated protein 33A_D41A_mutation Human genes 0.000 description 1
• 201000009693 Venezuelan hemorrhagic fever Diseases 0.000 description 1
• 108700022715 Viral Proteases Proteins 0.000 description 1
• 108010087302 Viral Structural Proteins Proteins 0.000 description 1
• 208000036142 Viral infection Diseases 0.000 description 1
• 241000710951 Western equine encephalitis virus Species 0.000 description 1
• 241000607479 Yersinia pestis Species 0.000 description 1
• 108010084455 Zeocin Proteins 0.000 description 1
• 230000002159 abnormal effect Effects 0.000 description 1
• 230000021736 acetylation Effects 0.000 description 1
• 238000006640 acetylation reaction Methods 0.000 description 1
• 229960004308 acetylcysteine Drugs 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 230000006786 activation induced cell death Effects 0.000 description 1
• 108700010877 adenoviridae proteins Proteins 0.000 description 1
• 230000002776 aggregation Effects 0.000 description 1
• 238000004220 aggregation Methods 0.000 description 1
• 101150045355 akt1 gene Proteins 0.000 description 1
• 230000003281 allosteric effect Effects 0.000 description 1
• 229950010482 alpelisib Drugs 0.000 description 1
• 230000004075 alteration Effects 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 102000006646 aminoglycoside phosphotransferase Human genes 0.000 description 1
• 206010002022 amyloidosis Diseases 0.000 description 1
• 239000005557 antagonist Substances 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 229940088710 antibiotic agent Drugs 0.000 description 1
• 239000000611 antibody drug conjugate Substances 0.000 description 1
• 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 1
• 229940049595 antibody-drug conjugate Drugs 0.000 description 1
• 210000000628 antibody-producing cell Anatomy 0.000 description 1
• 230000006907 apoptotic process Effects 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• 108010077245 asparaginyl-proline Proteins 0.000 description 1
• 239000012298 atmosphere Substances 0.000 description 1
• 108010044540 auristatin Proteins 0.000 description 1
• 230000001363 autoimmune Effects 0.000 description 1
• 201000000448 autoimmune hemolytic anemia Diseases 0.000 description 1
• 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 1
• 206010064097 avian influenza Diseases 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• 230000003115 biocidal effect Effects 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• 229960002685 biotin Drugs 0.000 description 1
• 235000020958 biotin Nutrition 0.000 description 1
• 239000011616 biotin Substances 0.000 description 1
• 229930189065 blasticidin Natural products 0.000 description 1
• 210000000988 bone and bone Anatomy 0.000 description 1
• 229960005520 bryostatin Drugs 0.000 description 1
• MJQUEDHRCUIRLF-TVIXENOKSA-N bryostatin 1 Chemical compound C([C@@H]1CC(/[C@@H]([C@@](C(C)(C)/C=C/2)(O)O1)OC(=O)/C=C/C=C/CCC)=C\C(=O)OC)[C@H]([C@@H](C)O)OC(=O)C[C@H](O)C[C@@H](O1)C[C@H](OC(C)=O)C(C)(C)[C@]1(O)C[C@@H]1C\C(=C\C(=O)OC)C[C@H]\2O1 MJQUEDHRCUIRLF-TVIXENOKSA-N 0.000 description 1
• MUIWQCKLQMOUAT-AKUNNTHJSA-N bryostatin 20 Natural products COC(=O)C=C1C[C@@]2(C)C[C@]3(O)O[C@](C)(C[C@@H](O)CC(=O)O[C@](C)(C[C@@]4(C)O[C@](O)(CC5=CC(=O)O[C@]45C)C(C)(C)C=C[C@@](C)(C1)O2)[C@@H](C)O)C[C@H](OC(=O)C(C)(C)C)C3(C)C MUIWQCKLQMOUAT-AKUNNTHJSA-N 0.000 description 1
• 229950003628 buparlisib Drugs 0.000 description 1
• 210000004899 c-terminal region Anatomy 0.000 description 1
• 239000003710 calcium ionophore Substances 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
• 101150058049 car gene Proteins 0.000 description 1
• 150000001720 carbohydrates Chemical class 0.000 description 1
• 235000014633 carbohydrates Nutrition 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 230000020411 cell activation Effects 0.000 description 1
• 239000006143 cell culture medium Substances 0.000 description 1
• 230000030833 cell death Effects 0.000 description 1
• 230000003915 cell function Effects 0.000 description 1
• 238000002659 cell therapy Methods 0.000 description 1
• 230000007969 cellular immunity Effects 0.000 description 1
• 230000019522 cellular metabolic process Effects 0.000 description 1
• 230000036755 cellular response Effects 0.000 description 1
• 239000003638 chemical reducing agent Substances 0.000 description 1
• 238000002512 chemotherapy Methods 0.000 description 1
• 235000019693 cherries Nutrition 0.000 description 1
• 210000000038 chest Anatomy 0.000 description 1
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
• 239000013611 chromosomal DNA Substances 0.000 description 1
• 238000004140 cleaning Methods 0.000 description 1
• 230000004186 co-expression Effects 0.000 description 1
• 230000002860 competitive effect Effects 0.000 description 1
• 230000001276 controlling effect Effects 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 230000008878 coupling Effects 0.000 description 1
• 238000010168 coupling process Methods 0.000 description 1
• 238000005859 coupling reaction Methods 0.000 description 1
• 239000012228 culture supernatant Substances 0.000 description 1
• 230000016396 cytokine production Effects 0.000 description 1
• 210000000805 cytoplasm Anatomy 0.000 description 1
• 239000003145 cytotoxic factor Substances 0.000 description 1
• 230000007402 cytotoxic response Effects 0.000 description 1
• 210000004443 dendritic cell Anatomy 0.000 description 1
• 208000025729 dengue disease Diseases 0.000 description 1
• 239000005547 deoxyribonucleotide Substances 0.000 description 1
• 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
• 230000003831 deregulation Effects 0.000 description 1
• 230000001627 detrimental effect Effects 0.000 description 1
• 238000010586 diagram Methods 0.000 description 1
• 206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 1
• 238000006471 dimerization reaction Methods 0.000 description 1
• DCSRPHQBFSYJNN-UHFFFAOYSA-L disodium 4-[(2-arsonophenyl)diazenyl]-3-hydroxynaphthalene-2,7-disulfonate Chemical compound [Na+].[Na+].Oc1c(N=Nc2ccccc2[As](O)(O)=O)c2ccc(cc2cc1S([O-])(=O)=O)S([O-])(=O)=O DCSRPHQBFSYJNN-UHFFFAOYSA-L 0.000 description 1
• 238000006073 displacement reaction Methods 0.000 description 1
• 238000010494 dissociation reaction Methods 0.000 description 1
• 230000005593 dissociations Effects 0.000 description 1
• 230000003828 downregulation Effects 0.000 description 1
• 238000009510 drug design Methods 0.000 description 1
• 230000002500 effect on skin Effects 0.000 description 1
• 230000002708 enhancing effect Effects 0.000 description 1
• 101150030339 env gene Proteins 0.000 description 1
• 230000001973 epigenetic effect Effects 0.000 description 1
• 102000015694 estrogen receptors Human genes 0.000 description 1
• 108010038795 estrogen receptors Proteins 0.000 description 1
• CJAONIOAQZUHPN-KKLWWLSJSA-N ethyl 12-[[2-[(2r,3r)-3-[2-[(12-ethoxy-12-oxododecyl)-methylamino]-2-oxoethoxy]butan-2-yl]oxyacetyl]-methylamino]dodecanoate Chemical compound CCOC(=O)CCCCCCCCCCCN(C)C(=O)CO[C@H](C)[C@@H](C)OCC(=O)N(C)CCCCCCCCCCCC(=O)OCC CJAONIOAQZUHPN-KKLWWLSJSA-N 0.000 description 1
• 102000013165 exonuclease Human genes 0.000 description 1
• 210000002744 extracellular matrix Anatomy 0.000 description 1
• 239000000284 extract Substances 0.000 description 1
• 201000006569 extramedullary plasmacytoma Diseases 0.000 description 1
• GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
• 201000003444 follicular lymphoma Diseases 0.000 description 1
• 238000005242 forging Methods 0.000 description 1
• 230000005714 functional activity Effects 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• 238000001476 gene delivery Methods 0.000 description 1
• 230000030279 gene silencing Effects 0.000 description 1
• 230000024924 glomerular filtration Effects 0.000 description 1
• 239000003862 glucocorticoid 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
• 108010020688 glycylhistidine Proteins 0.000 description 1
• 230000003394 haemopoietic effect Effects 0.000 description 1
• 238000003306 harvesting Methods 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 229910001385 heavy metal Inorganic materials 0.000 description 1
• 208000007475 hemolytic anemia Diseases 0.000 description 1
• IIRDTKBZINWQAW-UHFFFAOYSA-N hexaethylene glycol Chemical compound OCCOCCOCCOCCOCCOCCO IIRDTKBZINWQAW-UHFFFAOYSA-N 0.000 description 1
• 238000002744 homologous recombination Methods 0.000 description 1
• 230000006801 homologous recombination Effects 0.000 description 1
• 238000011577 humanized mouse model Methods 0.000 description 1
• 239000001257 hydrogen Substances 0.000 description 1
• 229910052739 hydrogen Inorganic materials 0.000 description 1
• 230000005660 hydrophilic surface Effects 0.000 description 1
• 230000002209 hydrophobic effect Effects 0.000 description 1
• 125000001165 hydrophobic group Chemical group 0.000 description 1
• 108010002685 hygromycin-B kinase Proteins 0.000 description 1
• 229960003445 idelalisib Drugs 0.000 description 1
• IFSDAJWBUCMOAH-HNNXBMFYSA-N idelalisib Chemical compound C1([C@@H](NC=2C=3N=CNC=3N=CN=2)CC)=NC2=CC=CC(F)=C2C(=O)N1C1=CC=CC=C1 IFSDAJWBUCMOAH-HNNXBMFYSA-N 0.000 description 1
• 230000005965 immune activity Effects 0.000 description 1
• 230000008073 immune recognition Effects 0.000 description 1
• 230000028993 immune response Effects 0.000 description 1
• 210000000987 immune system Anatomy 0.000 description 1
• 230000002163 immunogen Effects 0.000 description 1
• 229940072221 immunoglobulins Drugs 0.000 description 1
• 230000004957 immunoregulator effect Effects 0.000 description 1
• 230000001771 impaired effect Effects 0.000 description 1
• 208000015266 indolent plasma cell myeloma Diseases 0.000 description 1
• 239000000411 inducer Substances 0.000 description 1
• 208000037798 influenza B Diseases 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 238000007689 inspection Methods 0.000 description 1
• 229940125396 insulin Drugs 0.000 description 1
• 230000002452 interceptive effect Effects 0.000 description 1
• 229940079322 interferon Drugs 0.000 description 1
• 108010074108 interleukin-21 Proteins 0.000 description 1
• 230000000968 intestinal effect Effects 0.000 description 1
• 101150066555 lacZ gene Proteins 0.000 description 1
• 238000011031 large-scale manufacturing process Methods 0.000 description 1
• 238000001638 lipofection Methods 0.000 description 1
• 210000004185 liver Anatomy 0.000 description 1
• 210000002809 long lived plasma cell Anatomy 0.000 description 1
• 230000001926 lymphatic effect Effects 0.000 description 1
• 208000003747 lymphoid leukemia Diseases 0.000 description 1
• 230000036212 malign transformation Effects 0.000 description 1
• 230000035800 maturation Effects 0.000 description 1
• 210000003519 mature b lymphocyte Anatomy 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 210000003593 megakaryocyte Anatomy 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
• 108091062762 miR-21 stem-loop Proteins 0.000 description 1
• 108091041631 miR-21-1 stem-loop Proteins 0.000 description 1
• 108091044442 miR-21-2 stem-loop Proteins 0.000 description 1
• 239000010445 mica Substances 0.000 description 1
• 229910052618 mica group Inorganic materials 0.000 description 1
• VKHAHZOOUSRJNA-GCNJZUOMSA-N mifepristone Chemical compound C1([C@@H]2C3=C4CCC(=O)C=C4CC[C@H]3[C@@H]3CC[C@@]([C@]3(C2)C)(O)C#CC)=CC=C(N(C)C)C=C1 VKHAHZOOUSRJNA-GCNJZUOMSA-N 0.000 description 1
• 229960003248 mifepristone Drugs 0.000 description 1
• 238000001823 molecular biology technique Methods 0.000 description 1
• 201000005328 monoclonal gammopathy of uncertain significance Diseases 0.000 description 1
• 210000005087 mononuclear cell Anatomy 0.000 description 1
• 208000001725 mucocutaneous lymph node syndrome Diseases 0.000 description 1
• 201000006417 multiple sclerosis Diseases 0.000 description 1
• 238000002703 mutagenesis Methods 0.000 description 1
• 231100000350 mutagenesis Toxicity 0.000 description 1
• 208000025113 myeloid leukemia Diseases 0.000 description 1
• QTHCAAFKVUWAFI-DJKKODMXSA-N n-[(e)-(6-bromoimidazo[1,2-a]pyridin-3-yl)methylideneamino]-n,2-dimethyl-5-nitrobenzenesulfonamide Chemical compound C=1N=C2C=CC(Br)=CN2C=1/C=N/N(C)S(=O)(=O)C1=CC([N+]([O-])=O)=CC=C1C QTHCAAFKVUWAFI-DJKKODMXSA-N 0.000 description 1
• 108700004028 nef Genes Proteins 0.000 description 1
• 229960004927 neomycin Drugs 0.000 description 1
• 230000007935 neutral effect Effects 0.000 description 1
• 108091027963 non-coding RNA Proteins 0.000 description 1
• 102000042567 non-coding RNA Human genes 0.000 description 1
• 230000012223 nuclear import Effects 0.000 description 1
• 210000004940 nucleus Anatomy 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 150000002894 organic compounds Chemical class 0.000 description 1
• 201000009234 osteosclerotic myeloma Diseases 0.000 description 1
• 239000006174 pH buffer Substances 0.000 description 1
• 235000019834 papain Nutrition 0.000 description 1
• 229940055729 papain Drugs 0.000 description 1
• 230000036961 partial effect Effects 0.000 description 1
• 201000001976 pemphigus vulgaris Diseases 0.000 description 1
• 230000000149 penetrating effect Effects 0.000 description 1
• 230000035515 penetration Effects 0.000 description 1
• 229940049954 penicillin Drugs 0.000 description 1
• 229940111202 pepsin Drugs 0.000 description 1
• 239000000816 peptidomimetic Substances 0.000 description 1
• 229930192851 perforin Natural products 0.000 description 1
• 238000002823 phage display Methods 0.000 description 1
• 230000008782 phagocytosis Effects 0.000 description 1
• CWCMIVBLVUHDHK-ZSNHEYEWSA-N phleomycin D1 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC[C@@H](N=1)C=1SC=C(N=1)C(=O)NCCCCNC(N)=N)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C CWCMIVBLVUHDHK-ZSNHEYEWSA-N 0.000 description 1
• 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
• 150000003906 phosphoinositides Chemical class 0.000 description 1
• 102000020233 phosphotransferase Human genes 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• 230000035479 physiological effects, processes and functions Effects 0.000 description 1
• LHNIIDJUOCFXAP-UHFFFAOYSA-N pictrelisib Chemical compound C1CN(S(=O)(=O)C)CCN1CC1=CC2=NC(C=3C=4C=NNC=4C=CC=3)=NC(N3CCOCC3)=C2S1 LHNIIDJUOCFXAP-UHFFFAOYSA-N 0.000 description 1
• 208000031223 plasma cell leukemia Diseases 0.000 description 1
• 108010058237 plasma protein fraction Proteins 0.000 description 1
• 229940002993 plasmanate Drugs 0.000 description 1
• 239000013600 plasmid vector Substances 0.000 description 1
• 201000006292 polyarteritis nodosa Diseases 0.000 description 1
• 229920001282 polysaccharide Polymers 0.000 description 1
• 239000005017 polysaccharide Substances 0.000 description 1
• 150000004804 polysaccharides Chemical class 0.000 description 1
• 230000023603 positive regulation of transcription initiation, DNA-dependent Effects 0.000 description 1
• 208000017805 post-transplant lymphoproliferative disease Diseases 0.000 description 1
• 230000032361 posttranscriptional gene silencing Effects 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 244000144977 poultry Species 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 230000004224 protection Effects 0.000 description 1
• 238000000159 protein binding assay Methods 0.000 description 1
• 238000000746 purification Methods 0.000 description 1
• 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
• 229950010131 puromycin Drugs 0.000 description 1
• 238000001959 radiotherapy Methods 0.000 description 1
• ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 1
• 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
• 230000009712 regulation of translation Effects 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 230000000284 resting effect Effects 0.000 description 1
• 230000000717 retained effect Effects 0.000 description 1
• 201000006845 reticulosarcoma Diseases 0.000 description 1
• 208000029922 reticulum cell sarcoma Diseases 0.000 description 1
• 206010039083 rhinitis Diseases 0.000 description 1
• 239000002336 ribonucleotide Substances 0.000 description 1
• 125000002652 ribonucleotide group Chemical group 0.000 description 1
• 235000009566 rice Nutrition 0.000 description 1
• 102200128616 rs121908751 Human genes 0.000 description 1
• 102200052245 rs199469625 Human genes 0.000 description 1
• 102220139188 rs35702995 Human genes 0.000 description 1
• 102220237139 rs376184349 Human genes 0.000 description 1
• 102220045124 rs587781846 Human genes 0.000 description 1
• 102200155054 rs80358230 Human genes 0.000 description 1
• 238000002864 sequence alignment Methods 0.000 description 1
• 230000035939 shock Effects 0.000 description 1
• 229960002930 sirolimus Drugs 0.000 description 1
• DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 1
• 239000007787 solid Substances 0.000 description 1
• 230000006641 stabilisation Effects 0.000 description 1
• 238000011105 stabilization Methods 0.000 description 1
• 238000010186 staining Methods 0.000 description 1
• 229960005322 streptomycin Drugs 0.000 description 1
• 239000013589 supplement Substances 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 230000002194 synthesizing effect Effects 0.000 description 1
• 230000008718 systemic inflammatory response Effects 0.000 description 1
• URLYINUFLXOMHP-HTVVRFAVSA-N tcn-p Chemical compound C=12C3=NC=NC=1N(C)N=C(N)C2=CN3[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O URLYINUFLXOMHP-HTVVRFAVSA-N 0.000 description 1
• 101150065190 term gene Proteins 0.000 description 1
• 238000012360 testing method Methods 0.000 description 1
• 229960002180 tetracycline Drugs 0.000 description 1
• 229930101283 tetracycline Natural products 0.000 description 1
• 235000019364 tetracycline Nutrition 0.000 description 1
• 150000003522 tetracyclines Chemical class 0.000 description 1
• 238000010257 thawing Methods 0.000 description 1
• 238000011287 therapeutic dose Methods 0.000 description 1
• 125000003396 thiol group Chemical group [H]S* 0.000 description 1
• 229940113082 thymine Drugs 0.000 description 1
• 230000001256 tonic effect Effects 0.000 description 1
• 231100000331 toxic Toxicity 0.000 description 1
• 230000002588 toxic effect Effects 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 230000009752 translational inhibition Effects 0.000 description 1
• 230000014621 translational initiation 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
• ZIBGPFATKBEMQZ-UHFFFAOYSA-N triethylene glycol Chemical compound OCCOCCOCCO ZIBGPFATKBEMQZ-UHFFFAOYSA-N 0.000 description 1
• 230000004614 tumor growth Effects 0.000 description 1
• 102000003390 tumor necrosis factor Human genes 0.000 description 1
• 241000701447 unidentified baculovirus Species 0.000 description 1
• 241000712461 unidentified influenza virus Species 0.000 description 1
• 241001515965 unidentified phage Species 0.000 description 1
• 229940035893 uracil Drugs 0.000 description 1
• 210000003501 vero cell Anatomy 0.000 description 1
• 230000035899 viability Effects 0.000 description 1
• 230000009385 viral infection Effects 0.000 description 1
• 210000000605 viral structure Anatomy 0.000 description 1
• 230000006490 viral transcription Effects 0.000 description 1
• 108010071260 virus protein 2A Proteins 0.000 description 1
• 239000011782 vitamin Substances 0.000 description 1
• 229940088594 vitamin Drugs 0.000 description 1
• 229930003231 vitamin Natural products 0.000 description 1
• 235000013343 vitamin Nutrition 0.000 description 1
• QDLHCMPXEPAAMD-QAIWCSMKSA-N wortmannin Chemical compound C1([C@]2(C)C3=C(C4=O)OC=C3C(=O)O[C@@H]2COC)=C4[C@@H]2CCC(=O)[C@@]2(C)C[C@H]1OC(C)=O QDLHCMPXEPAAMD-QAIWCSMKSA-N 0.000 description 1
• QDLHCMPXEPAAMD-UHFFFAOYSA-N wortmannin Natural products COCC1OC(=O)C2=COC(C3=O)=C2C1(C)C1=C3C2CCC(=O)C2(C)CC1OC(C)=O QDLHCMPXEPAAMD-UHFFFAOYSA-N 0.000 description 1