ES2901215T3 - Péptidos y nanopartículas para la liberación intracelular de moléculas de edición del genoma - Google Patents
Péptidos y nanopartículas para la liberación intracelular de moléculas de edición del genoma Download PDFInfo
- Publication number
- ES2901215T3 ES2901215T3 ES17733918T ES17733918T ES2901215T3 ES 2901215 T3 ES2901215 T3 ES 2901215T3 ES 17733918 T ES17733918 T ES 17733918T ES 17733918 T ES17733918 T ES 17733918T ES 2901215 T3 ES2901215 T3 ES 2901215T3
- Authority
- ES
- Spain
- Prior art keywords
- cell
- genome editing
- nucleic acid
- complex
- target
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 238000010362 genome editing Methods 0.000 title claims abstract description 369
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 296
- 239000002105 nanoparticle Substances 0.000 title claims description 298
- 102000004196 processed proteins & peptides Human genes 0.000 title claims description 98
- 230000003834 intracellular effect Effects 0.000 title description 2
- 108010051109 Cell-Penetrating Peptides Proteins 0.000 claims abstract description 454
- 102000020313 Cell-Penetrating Peptides Human genes 0.000 claims abstract description 454
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 427
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 418
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 418
- 102000040430 polynucleotide Human genes 0.000 claims abstract description 319
- 108091033319 polynucleotide Proteins 0.000 claims abstract description 319
- 239000002157 polynucleotide Substances 0.000 claims abstract description 319
- 108020005004 Guide RNA Proteins 0.000 claims abstract description 108
- 108020004414 DNA Proteins 0.000 claims abstract description 84
- 230000000295 complement effect Effects 0.000 claims abstract description 68
- 108010042407 Endonucleases Proteins 0.000 claims abstract description 22
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract 11
- 108091033409 CRISPR Proteins 0.000 claims description 240
- 108090000623 proteins and genes Proteins 0.000 claims description 220
- 230000004048 modification Effects 0.000 claims description 163
- 238000012986 modification Methods 0.000 claims description 163
- 210000004027 cell Anatomy 0.000 claims description 148
- 150000001413 amino acids Chemical class 0.000 claims description 133
- 125000003729 nucleotide group Chemical group 0.000 claims description 93
- 230000014509 gene expression Effects 0.000 claims description 88
- 239000002773 nucleotide Substances 0.000 claims description 88
- 102000004169 proteins and genes Human genes 0.000 claims description 65
- 235000018102 proteins Nutrition 0.000 claims description 60
- -1 CTLA- 4 Proteins 0.000 claims description 48
- 230000008685 targeting Effects 0.000 claims description 46
- 235000001014 amino acid Nutrition 0.000 claims description 36
- 238000000034 method Methods 0.000 claims description 34
- 102000053602 DNA Human genes 0.000 claims description 32
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 31
- 238000007792 addition Methods 0.000 claims description 28
- 201000010099 disease Diseases 0.000 claims description 28
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 27
- 238000006467 substitution reaction Methods 0.000 claims description 27
- 238000003780 insertion Methods 0.000 claims description 26
- 230000037431 insertion Effects 0.000 claims description 26
- 102000005962 receptors Human genes 0.000 claims description 25
- 108020003175 receptors Proteins 0.000 claims description 25
- 241000282414 Homo sapiens Species 0.000 claims description 24
- 206010028980 Neoplasm Diseases 0.000 claims description 23
- 238000012217 deletion Methods 0.000 claims description 23
- 230000037430 deletion Effects 0.000 claims description 23
- 108091034117 Oligonucleotide Proteins 0.000 claims description 22
- 239000008194 pharmaceutical composition Substances 0.000 claims description 21
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 20
- 102100031780 Endonuclease Human genes 0.000 claims description 18
- 108020004682 Single-Stranded DNA Proteins 0.000 claims description 16
- 201000011510 cancer Diseases 0.000 claims description 15
- 230000002093 peripheral effect Effects 0.000 claims description 14
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 claims description 13
- 102000004127 Cytokines Human genes 0.000 claims description 12
- 108090000695 Cytokines Proteins 0.000 claims description 12
- 210000002950 fibroblast Anatomy 0.000 claims description 11
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 10
- 229940123611 Genome editing Drugs 0.000 claims description 9
- 102100034343 Integrase Human genes 0.000 claims description 9
- 108010061833 Integrases Proteins 0.000 claims description 9
- 230000003612 virological effect Effects 0.000 claims description 9
- UFULAYFCSOUIOV-UHFFFAOYSA-N cysteamine Chemical compound NCCS UFULAYFCSOUIOV-UHFFFAOYSA-N 0.000 claims description 8
- 238000011161 development Methods 0.000 claims description 8
- 230000018109 developmental process Effects 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- 235000012000 cholesterol Nutrition 0.000 claims description 7
- 150000002632 lipids Chemical class 0.000 claims description 7
- 229920001223 polyethylene glycol Polymers 0.000 claims description 7
- 208000035473 Communicable disease Diseases 0.000 claims description 6
- 208000026350 Inborn Genetic disease Diseases 0.000 claims description 6
- 108010066154 Nuclear Export Signals Proteins 0.000 claims description 6
- 108010077850 Nuclear Localization Signals Proteins 0.000 claims description 6
- 239000002202 Polyethylene glycol Substances 0.000 claims description 6
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 6
- 229930195729 fatty acid Natural products 0.000 claims description 6
- 239000000194 fatty acid Substances 0.000 claims description 6
- 150000004665 fatty acids Chemical class 0.000 claims description 6
- 150000004676 glycans Chemical class 0.000 claims description 6
- 210000003494 hepatocyte Anatomy 0.000 claims description 6
- 208000027866 inflammatory disease Diseases 0.000 claims description 6
- 229920001282 polysaccharide Polymers 0.000 claims description 6
- 239000005017 polysaccharide Substances 0.000 claims description 6
- 230000006798 recombination Effects 0.000 claims description 6
- 238000005215 recombination Methods 0.000 claims description 6
- JPSHPWJJSVEEAX-OWPBQMJCSA-N (2s)-2-amino-4-fluoranylpentanedioic acid Chemical compound OC(=O)[C@@H](N)CC([18F])C(O)=O JPSHPWJJSVEEAX-OWPBQMJCSA-N 0.000 claims description 5
- 102100027207 CD27 antigen Human genes 0.000 claims description 5
- 108010007712 Hepatitis A Virus Cellular Receptor 1 Proteins 0.000 claims description 5
- 102100034459 Hepatitis A virus cellular receptor 1 Human genes 0.000 claims description 5
- 101000914511 Homo sapiens CD27 antigen Proteins 0.000 claims description 5
- 102100022153 Tumor necrosis factor receptor superfamily member 4 Human genes 0.000 claims description 5
- 101710165473 Tumor necrosis factor receptor superfamily member 4 Proteins 0.000 claims description 5
- 230000032683 aging Effects 0.000 claims description 5
- 210000004899 c-terminal region Anatomy 0.000 claims description 5
- 239000003102 growth factor Substances 0.000 claims description 5
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 5
- 238000013518 transcription Methods 0.000 claims description 5
- 230000035897 transcription Effects 0.000 claims description 5
- 102100029822 B- and T-lymphocyte attenuator Human genes 0.000 claims description 4
- 108010074708 B7-H1 Antigen Proteins 0.000 claims description 4
- 102000000844 Cell Surface Receptors Human genes 0.000 claims description 4
- 108010001857 Cell Surface Receptors Proteins 0.000 claims description 4
- 102100034458 Hepatitis A virus cellular receptor 2 Human genes 0.000 claims description 4
- 101710083479 Hepatitis A virus cellular receptor 2 homolog Proteins 0.000 claims description 4
- 101000864344 Homo sapiens B- and T-lymphocyte attenuator Proteins 0.000 claims description 4
- 101000831007 Homo sapiens T-cell immunoreceptor with Ig and ITIM domains Proteins 0.000 claims description 4
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 claims description 4
- 101000801234 Homo sapiens Tumor necrosis factor receptor superfamily member 18 Proteins 0.000 claims description 4
- 101000851370 Homo sapiens Tumor necrosis factor receptor superfamily member 9 Proteins 0.000 claims description 4
- 101000666896 Homo sapiens V-type immunoglobulin domain-containing suppressor of T-cell activation Proteins 0.000 claims description 4
- 102000017578 LAG3 Human genes 0.000 claims description 4
- 101150030213 Lag3 gene Proteins 0.000 claims description 4
- 108010061593 Member 14 Tumor Necrosis Factor Receptors Proteins 0.000 claims description 4
- 208000024556 Mendelian disease Diseases 0.000 claims description 4
- 206010027476 Metastases Diseases 0.000 claims description 4
- 101100407308 Mus musculus Pdcd1lg2 gene Proteins 0.000 claims description 4
- 108700030875 Programmed Cell Death 1 Ligand 2 Proteins 0.000 claims description 4
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 claims description 4
- 102100024213 Programmed cell death 1 ligand 2 Human genes 0.000 claims description 4
- 102000001253 Protein Kinase Human genes 0.000 claims description 4
- 229940126547 T-cell immunoglobulin mucin-3 Drugs 0.000 claims description 4
- 102100024834 T-cell immunoreceptor with Ig and ITIM domains Human genes 0.000 claims description 4
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 claims description 4
- 102100033728 Tumor necrosis factor receptor superfamily member 18 Human genes 0.000 claims description 4
- 102100036856 Tumor necrosis factor receptor superfamily member 9 Human genes 0.000 claims description 4
- 102100038282 V-type immunoglobulin domain-containing suppressor of T-cell activation Human genes 0.000 claims description 4
- 230000006907 apoptotic process Effects 0.000 claims description 4
- 230000003176 fibrotic effect Effects 0.000 claims description 4
- IJJVMEJXYNJXOJ-UHFFFAOYSA-N fluquinconazole Chemical compound C=1C=C(Cl)C=C(Cl)C=1N1C(=O)C2=CC(F)=CC=C2N=C1N1C=NC=N1 IJJVMEJXYNJXOJ-UHFFFAOYSA-N 0.000 claims description 4
- 238000000338 in vitro Methods 0.000 claims description 4
- 208000015181 infectious disease Diseases 0.000 claims description 4
- 210000004072 lung Anatomy 0.000 claims description 4
- 230000009401 metastasis Effects 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 108060006633 protein kinase Proteins 0.000 claims description 4
- 230000011664 signaling Effects 0.000 claims description 4
- 150000003573 thiols Chemical class 0.000 claims description 4
- 206010016654 Fibrosis Diseases 0.000 claims description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 3
- 102000040945 Transcription factor Human genes 0.000 claims description 3
- 108091023040 Transcription factor Proteins 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 3
- 150000001408 amides Chemical class 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 235000018417 cysteine Nutrition 0.000 claims description 3
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 3
- 230000004761 fibrosis Effects 0.000 claims description 3
- 210000004185 liver Anatomy 0.000 claims description 3
- 208000014018 liver neoplasm Diseases 0.000 claims description 3
- MGFYIUFZLHCRTH-UHFFFAOYSA-N nitrilotriacetic acid Chemical class OC(=O)CN(CC(O)=O)CC(O)=O MGFYIUFZLHCRTH-UHFFFAOYSA-N 0.000 claims description 3
- 150000003904 phospholipids Chemical class 0.000 claims description 3
- 208000002250 Hematologic Neoplasms Diseases 0.000 claims description 2
- 208000028782 Hereditary disease Diseases 0.000 claims description 2
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 2
- 208000019693 Lung disease Diseases 0.000 claims description 2
- 206010038389 Renal cancer Diseases 0.000 claims description 2
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 2
- 210000004443 dendritic cell Anatomy 0.000 claims description 2
- 206010012601 diabetes mellitus Diseases 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 208000030533 eye disease Diseases 0.000 claims description 2
- 208000016361 genetic disease Diseases 0.000 claims description 2
- 210000003714 granulocyte Anatomy 0.000 claims description 2
- 201000005787 hematologic cancer Diseases 0.000 claims description 2
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 claims description 2
- 210000003630 histaminocyte Anatomy 0.000 claims description 2
- 201000010982 kidney cancer Diseases 0.000 claims description 2
- 201000007270 liver cancer Diseases 0.000 claims description 2
- 208000019423 liver disease Diseases 0.000 claims description 2
- 201000005202 lung cancer Diseases 0.000 claims description 2
- 208000020816 lung neoplasm Diseases 0.000 claims description 2
- 210000001616 monocyte Anatomy 0.000 claims description 2
- 210000000822 natural killer cell Anatomy 0.000 claims description 2
- 210000002569 neuron Anatomy 0.000 claims description 2
- 150000003335 secondary amines Chemical class 0.000 claims description 2
- 210000000130 stem cell Anatomy 0.000 claims description 2
- 102100023990 60S ribosomal protein L17 Human genes 0.000 claims 1
- 102000012220 Member 14 Tumor Necrosis Factor Receptors Human genes 0.000 claims 1
- 101710089372 Programmed cell death protein 1 Proteins 0.000 claims 1
- 230000005856 abnormality Effects 0.000 claims 1
- 102000004533 Endonucleases Human genes 0.000 abstract description 4
- 108020004999 messenger RNA Proteins 0.000 description 47
- 102000004190 Enzymes Human genes 0.000 description 42
- 108090000790 Enzymes Proteins 0.000 description 42
- 229940088598 enzyme Drugs 0.000 description 42
- 108091079001 CRISPR RNA Proteins 0.000 description 41
- 239000000047 product Substances 0.000 description 39
- 101710163270 Nuclease Proteins 0.000 description 37
- 239000013612 plasmid Substances 0.000 description 37
- 108091026890 Coding region Proteins 0.000 description 35
- 239000012097 Lipofectamine 2000 Substances 0.000 description 25
- 239000012634 fragment Substances 0.000 description 24
- 239000003446 ligand Substances 0.000 description 23
- 230000004077 genetic alteration Effects 0.000 description 22
- 231100000118 genetic alteration Toxicity 0.000 description 22
- 230000027455 binding Effects 0.000 description 21
- 229920001184 polypeptide Polymers 0.000 description 21
- 239000012098 Lipofectamine RNAiMAX Substances 0.000 description 20
- 230000001965 increasing effect Effects 0.000 description 19
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 18
- 108700008625 Reporter Genes Proteins 0.000 description 18
- 230000002222 downregulating effect Effects 0.000 description 17
- 108010048367 enhanced green fluorescent protein Proteins 0.000 description 17
- 238000000684 flow cytometry Methods 0.000 description 17
- 230000001404 mediated effect Effects 0.000 description 17
- 108020004705 Codon Proteins 0.000 description 15
- 239000000427 antigen Substances 0.000 description 15
- 108091007433 antigens Proteins 0.000 description 15
- 102000036639 antigens Human genes 0.000 description 15
- 238000003556 assay Methods 0.000 description 13
- 101001048956 Homo sapiens Homeobox protein EMX1 Proteins 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- 238000001727 in vivo Methods 0.000 description 11
- 239000000126 substance Substances 0.000 description 11
- 210000001519 tissue Anatomy 0.000 description 11
- 238000002965 ELISA Methods 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 10
- 238000011156 evaluation Methods 0.000 description 10
- 239000004215 Carbon black (E152) Substances 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 9
- 239000013613 expression plasmid Substances 0.000 description 9
- 229930195733 hydrocarbon Natural products 0.000 description 9
- 230000001988 toxicity Effects 0.000 description 9
- 231100000419 toxicity Toxicity 0.000 description 9
- 238000000134 MTT assay Methods 0.000 description 8
- 231100000002 MTT assay Toxicity 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- 239000002245 particle Substances 0.000 description 8
- 238000011002 quantification Methods 0.000 description 8
- 239000002344 surface layer Substances 0.000 description 8
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 7
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 7
- 241000699666 Mus <mouse, genus> Species 0.000 description 7
- 108091028043 Nucleic acid sequence Proteins 0.000 description 7
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 7
- 102100040247 Tumor necrosis factor Human genes 0.000 description 7
- 238000003776 cleavage reaction Methods 0.000 description 7
- 238000006471 dimerization reaction Methods 0.000 description 7
- 238000009396 hybridization Methods 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- 230000007017 scission Effects 0.000 description 7
- 108010002350 Interleukin-2 Proteins 0.000 description 6
- 102000000588 Interleukin-2 Human genes 0.000 description 6
- 241000193996 Streptococcus pyogenes Species 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
- 108700010070 Codon Usage Proteins 0.000 description 5
- 101150021185 FGF gene Proteins 0.000 description 5
- 108091092584 GDNA Proteins 0.000 description 5
- 102100023823 Homeobox protein EMX1 Human genes 0.000 description 5
- 108010065805 Interleukin-12 Proteins 0.000 description 5
- 102000013462 Interleukin-12 Human genes 0.000 description 5
- 102100034256 Mucin-1 Human genes 0.000 description 5
- 108010008707 Mucin-1 Proteins 0.000 description 5
- 238000010459 TALEN Methods 0.000 description 5
- 108010043645 Transcription Activator-Like Effector Nucleases Proteins 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 5
- 230000035772 mutation Effects 0.000 description 5
- 238000001890 transfection Methods 0.000 description 5
- 210000004881 tumor cell Anatomy 0.000 description 5
- 101150013553 CD40 gene Proteins 0.000 description 4
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 4
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 4
- 108091008036 Immune checkpoint proteins Proteins 0.000 description 4
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 4
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 4
- 108090000174 Interleukin-10 Proteins 0.000 description 4
- 102000003814 Interleukin-10 Human genes 0.000 description 4
- 102100025584 Leukocyte immunoglobulin-like receptor subfamily B member 1 Human genes 0.000 description 4
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 4
- 108020004566 Transfer RNA Proteins 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 4
- 210000003527 eukaryotic cell Anatomy 0.000 description 4
- 108020004201 indoleamine 2,3-dioxygenase Proteins 0.000 description 4
- 102000006639 indoleamine 2,3-dioxygenase Human genes 0.000 description 4
- 230000006780 non-homologous end joining Effects 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 101150051188 Adora2a gene Proteins 0.000 description 3
- 101710095342 Apolipoprotein B Proteins 0.000 description 3
- 102100040202 Apolipoprotein B-100 Human genes 0.000 description 3
- 206010006187 Breast cancer Diseases 0.000 description 3
- 208000026310 Breast neoplasm Diseases 0.000 description 3
- 108010040467 CRISPR-Associated Proteins Proteins 0.000 description 3
- 108010008532 Deoxyribonuclease I Proteins 0.000 description 3
- 102000007260 Deoxyribonuclease I Human genes 0.000 description 3
- 101000721661 Homo sapiens Cellular tumor antigen p53 Proteins 0.000 description 3
- 101000633784 Homo sapiens SLAM family member 7 Proteins 0.000 description 3
- 102100034389 Low density lipoprotein receptor adapter protein 1 Human genes 0.000 description 3
- 101710200421 Low density lipoprotein receptor adapter protein 1 Proteins 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 101100519207 Mus musculus Pdcd1 gene Proteins 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 3
- 101710111747 Peptidyl-prolyl cis-trans isomerase FKBP12 Proteins 0.000 description 3
- 108091028664 Ribonucleotide Proteins 0.000 description 3
- 102100029198 SLAM family member 7 Human genes 0.000 description 3
- 102100023085 Serine/threonine-protein kinase mTOR Human genes 0.000 description 3
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 3
- 102100028785 Tumor necrosis factor receptor superfamily member 14 Human genes 0.000 description 3
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 3
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 3
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 3
- 102000015736 beta 2-Microglobulin Human genes 0.000 description 3
- 108010081355 beta 2-Microglobulin Proteins 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 238000001415 gene therapy Methods 0.000 description 3
- 238000003384 imaging method Methods 0.000 description 3
- 238000010253 intravenous injection Methods 0.000 description 3
- 125000005647 linker group Chemical group 0.000 description 3
- 238000005457 optimization Methods 0.000 description 3
- 230000000149 penetrating effect Effects 0.000 description 3
- 210000004986 primary T-cell Anatomy 0.000 description 3
- 239000002336 ribonucleotide Substances 0.000 description 3
- 125000006850 spacer group Chemical group 0.000 description 3
- 230000000087 stabilizing effect Effects 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 239000013598 vector Substances 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 2
- YXHLJMWYDTXDHS-IRFLANFNSA-N 7-aminoactinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=C(N)C=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 YXHLJMWYDTXDHS-IRFLANFNSA-N 0.000 description 2
- 108700012813 7-aminoactinomycin D Proteins 0.000 description 2
- 108091093088 Amplicon Proteins 0.000 description 2
- 101001005269 Arabidopsis thaliana Ceramide synthase 1 LOH3 Proteins 0.000 description 2
- 101001005312 Arabidopsis thaliana Ceramide synthase LOH1 Proteins 0.000 description 2
- 108700020462 BRCA2 Proteins 0.000 description 2
- 102000052609 BRCA2 Human genes 0.000 description 2
- 101150008921 Brca2 gene Proteins 0.000 description 2
- 102100038078 CD276 antigen Human genes 0.000 description 2
- 108010029697 CD40 Ligand Proteins 0.000 description 2
- 102100032937 CD40 ligand Human genes 0.000 description 2
- 102100036008 CD48 antigen Human genes 0.000 description 2
- 108091007914 CDKs Proteins 0.000 description 2
- QCMYYKRYFNMIEC-UHFFFAOYSA-N COP(O)=O Chemical class COP(O)=O QCMYYKRYFNMIEC-UHFFFAOYSA-N 0.000 description 2
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 2
- 229940045513 CTLA4 antagonist Drugs 0.000 description 2
- 108010022366 Carcinoembryonic Antigen Proteins 0.000 description 2
- 102100025475 Carcinoembryonic antigen-related cell adhesion molecule 5 Human genes 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 2
- 102220605874 Cytosolic arginine sensor for mTORC1 subunit 2_D10A_mutation Human genes 0.000 description 2
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 description 2
- 230000007018 DNA scission Effects 0.000 description 2
- 101150029707 ERBB2 gene Proteins 0.000 description 2
- 101100007581 Entamoeba histolytica CPP1 gene Proteins 0.000 description 2
- 108010039471 Fas Ligand Protein Proteins 0.000 description 2
- 102100030708 GTPase KRas Human genes 0.000 description 2
- 102000004862 Gastrin releasing peptide Human genes 0.000 description 2
- 108090001053 Gastrin releasing peptide Proteins 0.000 description 2
- 229930186217 Glycolipid Natural products 0.000 description 2
- 101150050733 Gnas gene Proteins 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101000779641 Homo sapiens ALK tyrosine kinase receptor Proteins 0.000 description 2
- 101000716130 Homo sapiens CD48 antigen Proteins 0.000 description 2
- 101000584612 Homo sapiens GTPase KRas Proteins 0.000 description 2
- 101001034652 Homo sapiens Insulin-like growth factor 1 receptor Proteins 0.000 description 2
- 101000998146 Homo sapiens Interleukin-17A Proteins 0.000 description 2
- 101000984190 Homo sapiens Leukocyte immunoglobulin-like receptor subfamily B member 1 Proteins 0.000 description 2
- 101000984189 Homo sapiens Leukocyte immunoglobulin-like receptor subfamily B member 2 Proteins 0.000 description 2
- 101000868279 Homo sapiens Leukocyte surface antigen CD47 Proteins 0.000 description 2
- 101000863873 Homo sapiens Tyrosine-protein phosphatase non-receptor type substrate 1 Proteins 0.000 description 2
- 108010091358 Hypoxanthine Phosphoribosyltransferase Proteins 0.000 description 2
- 102100034980 ICOS ligand Human genes 0.000 description 2
- 102000037982 Immune checkpoint proteins Human genes 0.000 description 2
- 102100039688 Insulin-like growth factor 1 receptor Human genes 0.000 description 2
- 108010002352 Interleukin-1 Proteins 0.000 description 2
- 102000000589 Interleukin-1 Human genes 0.000 description 2
- 108090000176 Interleukin-13 Proteins 0.000 description 2
- 102000003816 Interleukin-13 Human genes 0.000 description 2
- 108090000172 Interleukin-15 Proteins 0.000 description 2
- 102100033461 Interleukin-17A Human genes 0.000 description 2
- 108090000978 Interleukin-4 Proteins 0.000 description 2
- 102000000743 Interleukin-5 Human genes 0.000 description 2
- 108010002616 Interleukin-5 Proteins 0.000 description 2
- 108090001005 Interleukin-6 Proteins 0.000 description 2
- 102000004889 Interleukin-6 Human genes 0.000 description 2
- 108010002586 Interleukin-7 Proteins 0.000 description 2
- 108010043610 KIR Receptors Proteins 0.000 description 2
- 102000002698 KIR Receptors Human genes 0.000 description 2
- 102000011782 Keratins Human genes 0.000 description 2
- 108010076876 Keratins Proteins 0.000 description 2
- 102000007330 LDL Lipoproteins Human genes 0.000 description 2
- 108010007622 LDL Lipoproteins Proteins 0.000 description 2
- 102100025583 Leukocyte immunoglobulin-like receptor subfamily B member 2 Human genes 0.000 description 2
- 101710145805 Leukocyte immunoglobulin-like receptor subfamily B member 3 Proteins 0.000 description 2
- 102100032913 Leukocyte surface antigen CD47 Human genes 0.000 description 2
- 108060001084 Luciferase Proteins 0.000 description 2
- 239000005089 Luciferase Substances 0.000 description 2
- 239000000637 Melanocyte-Stimulating Hormone Substances 0.000 description 2
- 108010007013 Melanocyte-Stimulating Hormones Proteins 0.000 description 2
- 108700011259 MicroRNAs Proteins 0.000 description 2
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 2
- 108020004711 Nucleic Acid Probes Proteins 0.000 description 2
- 102000002488 Nucleoplasmin Human genes 0.000 description 2
- 108010011536 PTEN Phosphohydrolase Proteins 0.000 description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 2
- 108091093037 Peptide nucleic acid Proteins 0.000 description 2
- 102100032543 Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN Human genes 0.000 description 2
- 108010072866 Prostate-Specific Antigen Proteins 0.000 description 2
- 102100038358 Prostate-specific antigen Human genes 0.000 description 2
- 108020004459 Small interfering RNA Proteins 0.000 description 2
- 101000668858 Spinacia oleracea 30S ribosomal protein S1, chloroplastic Proteins 0.000 description 2
- 101000898746 Streptomyces clavuligerus Clavaminate synthase 1 Proteins 0.000 description 2
- 102100039367 T-cell immunoglobulin and mucin domain-containing protein 4 Human genes 0.000 description 2
- 101710174757 T-cell immunoglobulin and mucin domain-containing protein 4 Proteins 0.000 description 2
- 102000018679 Tacrolimus Binding Proteins Human genes 0.000 description 2
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 2
- 102100031988 Tumor necrosis factor ligand superfamily member 6 Human genes 0.000 description 2
- 102100029948 Tyrosine-protein phosphatase non-receptor type substrate 1 Human genes 0.000 description 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
- 102100038929 V-set domain-containing T-cell activation inhibitor 1 Human genes 0.000 description 2
- 108091008605 VEGF receptors Proteins 0.000 description 2
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 2
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 2
- 108020000999 Viral RNA Proteins 0.000 description 2
- 230000021736 acetylation Effects 0.000 description 2
- 238000006640 acetylation reaction Methods 0.000 description 2
- 230000000692 anti-sense effect Effects 0.000 description 2
- 230000030741 antigen processing and presentation Effects 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical group NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 239000002458 cell surface marker Substances 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 239000005547 deoxyribonucleotide Substances 0.000 description 2
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 230000000447 dimerizing effect Effects 0.000 description 2
- 238000010494 dissociation reaction Methods 0.000 description 2
- 230000005593 dissociations Effects 0.000 description 2
- 239000002158 endotoxin Substances 0.000 description 2
- 239000004744 fabric Substances 0.000 description 2
- 108700014844 flt3 ligand Proteins 0.000 description 2
- PUBCCFNQJQKCNC-XKNFJVFFSA-N gastrin-releasingpeptide Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)CNC(=O)[C@H](C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)C(C)C)[C@@H](C)O)C(C)C)[C@@H](C)O)C(C)C)C1=CNC=N1 PUBCCFNQJQKCNC-XKNFJVFFSA-N 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 108010074108 interleukin-21 Proteins 0.000 description 2
- 229920006008 lipopolysaccharide Polymers 0.000 description 2
- 108010026228 mRNA guanylyltransferase Proteins 0.000 description 2
- 230000005291 magnetic effect Effects 0.000 description 2
- 201000001441 melanoma Diseases 0.000 description 2
- 239000002679 microRNA Substances 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 238000002703 mutagenesis Methods 0.000 description 2
- 231100000350 mutagenesis Toxicity 0.000 description 2
- 210000003098 myoblast Anatomy 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000002853 nucleic acid probe Substances 0.000 description 2
- 108060005597 nucleoplasmin Proteins 0.000 description 2
- 210000004940 nucleus Anatomy 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 2
- 150000003212 purines Chemical class 0.000 description 2
- 150000003230 pyrimidines Chemical class 0.000 description 2
- 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 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 108091008146 restriction endonucleases Proteins 0.000 description 2
- 238000007894 restriction fragment length polymorphism technique Methods 0.000 description 2
- 125000002652 ribonucleotide group Chemical group 0.000 description 2
- 229960002930 sirolimus Drugs 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
- 239000000344 soap Substances 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
- 238000000954 titration curve Methods 0.000 description 2
- 108091006106 transcriptional activators Proteins 0.000 description 2
- 230000035899 viability Effects 0.000 description 2
- VGONTNSXDCQUGY-RRKCRQDMSA-N 2'-deoxyinosine Chemical group C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC2=O)=C2N=C1 VGONTNSXDCQUGY-RRKCRQDMSA-N 0.000 description 1
- ASJSAQIRZKANQN-CRCLSJGQSA-N 2-deoxy-D-ribose Chemical compound OC[C@@H](O)[C@@H](O)CC=O ASJSAQIRZKANQN-CRCLSJGQSA-N 0.000 description 1
- HVCOBJNICQPDBP-UHFFFAOYSA-N 3-[3-[3,5-dihydroxy-6-methyl-4-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid;hydrate Chemical compound O.OC1C(OC(CC(=O)OC(CCCCCCC)CC(O)=O)CCCCCCC)OC(C)C(O)C1OC1C(O)C(O)C(O)C(C)O1 HVCOBJNICQPDBP-UHFFFAOYSA-N 0.000 description 1
- WEVYNIUIFUYDGI-UHFFFAOYSA-N 3-[6-[4-(trifluoromethoxy)anilino]-4-pyrimidinyl]benzamide Chemical compound NC(=O)C1=CC=CC(C=2N=CN=C(NC=3C=CC(OC(F)(F)F)=CC=3)C=2)=C1 WEVYNIUIFUYDGI-UHFFFAOYSA-N 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- XXLPVQZYQCGXOV-UHFFFAOYSA-N 4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one 2-hydroxypropanoic acid Chemical compound CC(O)C(O)=O.CC(O)C(O)=O.CN1CCN(CC1)c1ccc2nc([nH]c2c1)-c1c(N)c2c(F)cccc2[nH]c1=O XXLPVQZYQCGXOV-UHFFFAOYSA-N 0.000 description 1
- 102100026802 72 kDa type IV collagenase Human genes 0.000 description 1
- 101710151806 72 kDa type IV collagenase Proteins 0.000 description 1
- ZKRFOXLVOKTUTA-KQYNXXCUSA-N 9-(5-phosphoribofuranosyl)-6-mercaptopurine Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(O)=O)O[C@H]1N1C(NC=NC2=S)=C2N=C1 ZKRFOXLVOKTUTA-KQYNXXCUSA-N 0.000 description 1
- 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 description 1
- 102000017919 ADRB2 Human genes 0.000 description 1
- 102100033391 ATP-dependent RNA helicase DDX3X Human genes 0.000 description 1
- 241000604451 Acidaminococcus Species 0.000 description 1
- 241000093740 Acidaminococcus sp. Species 0.000 description 1
- 241000589291 Acinetobacter Species 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 108050000203 Adenosine receptors Proteins 0.000 description 1
- 102000009346 Adenosine receptors Human genes 0.000 description 1
- 101150078577 Adora2b gene Proteins 0.000 description 1
- 241000567147 Aeropyrum Species 0.000 description 1
- 108010080691 Alcohol O-acetyltransferase Proteins 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- 241000192542 Anabaena Species 0.000 description 1
- 102000009840 Angiopoietins Human genes 0.000 description 1
- 108010009906 Angiopoietins Proteins 0.000 description 1
- 102000008873 Angiotensin II receptor Human genes 0.000 description 1
- 108050000824 Angiotensin II receptor Proteins 0.000 description 1
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 1
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 1
- 108091023037 Aptamer Proteins 0.000 description 1
- 241000207208 Aquifex Species 0.000 description 1
- 241000205046 Archaeoglobus Species 0.000 description 1
- 102000008682 Argonaute Proteins Human genes 0.000 description 1
- 108010088141 Argonaute Proteins Proteins 0.000 description 1
- 102000003916 Arrestin Human genes 0.000 description 1
- 108090000328 Arrestin Proteins 0.000 description 1
- 102000005427 Asialoglycoprotein Receptor Human genes 0.000 description 1
- 108700020463 BRCA1 Proteins 0.000 description 1
- 108700040618 BRCA1 Genes Proteins 0.000 description 1
- 101150072950 BRCA1 gene Proteins 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 102100021663 Baculoviral IAP repeat-containing protein 5 Human genes 0.000 description 1
- 102100021894 Bcl-2-like protein 12 Human genes 0.000 description 1
- 102100025401 Breast cancer type 1 susceptibility protein Human genes 0.000 description 1
- 208000011691 Burkitt lymphomas Diseases 0.000 description 1
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 1
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 description 1
- 102100034808 CCAAT/enhancer-binding protein alpha Human genes 0.000 description 1
- 102100031168 CCN family member 2 Human genes 0.000 description 1
- 238000010354 CRISPR gene editing Methods 0.000 description 1
- 238000010446 CRISPR interference Methods 0.000 description 1
- 101150018129 CSF2 gene Proteins 0.000 description 1
- 101150069031 CSN2 gene Proteins 0.000 description 1
- 101100026251 Caenorhabditis elegans atf-2 gene Proteins 0.000 description 1
- 101100463133 Caenorhabditis elegans pdl-1 gene Proteins 0.000 description 1
- 241000589876 Campylobacter Species 0.000 description 1
- 102100032616 Caspase-2 Human genes 0.000 description 1
- 108090000552 Caspase-2 Proteins 0.000 description 1
- 102100026550 Caspase-9 Human genes 0.000 description 1
- 108090000566 Caspase-9 Proteins 0.000 description 1
- 102100028914 Catenin beta-1 Human genes 0.000 description 1
- 101150079049 Ccnd2 gene Proteins 0.000 description 1
- 241000191366 Chlorobium Species 0.000 description 1
- 241000588881 Chromobacterium Species 0.000 description 1
- 241000193403 Clostridium Species 0.000 description 1
- 108010043471 Core Binding Factor Alpha 2 Subunit Proteins 0.000 description 1
- 241000186216 Corynebacterium Species 0.000 description 1
- 101150074775 Csf1 gene Proteins 0.000 description 1
- 108010045171 Cyclic AMP Response Element-Binding Protein Proteins 0.000 description 1
- 102000005636 Cyclic AMP Response Element-Binding Protein Human genes 0.000 description 1
- 102000008130 Cyclic AMP-Dependent Protein Kinases Human genes 0.000 description 1
- 102100026359 Cyclic AMP-responsive element-binding protein 1 Human genes 0.000 description 1
- 102000016736 Cyclin Human genes 0.000 description 1
- 108050006400 Cyclin Proteins 0.000 description 1
- 102100025191 Cyclin-A2 Human genes 0.000 description 1
- 102100024458 Cyclin-dependent kinase inhibitor 2A Human genes 0.000 description 1
- 108090000266 Cyclin-dependent kinases Proteins 0.000 description 1
- 102000003903 Cyclin-dependent kinases Human genes 0.000 description 1
- 101100077740 Cyprinus carpio map2k2 gene Proteins 0.000 description 1
- 108010019961 Cysteine-Rich Protein 61 Proteins 0.000 description 1
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
- 101150017921 DDIT3 gene Proteins 0.000 description 1
- 102100029816 DEP domain-containing mTOR-interacting protein Human genes 0.000 description 1
- 102100024810 DNA (cytosine-5)-methyltransferase 3B Human genes 0.000 description 1
- 101710123222 DNA (cytosine-5)-methyltransferase 3B Proteins 0.000 description 1
- 102100028843 DNA mismatch repair protein Mlh1 Human genes 0.000 description 1
- 102100034157 DNA mismatch repair protein Msh2 Human genes 0.000 description 1
- 102100021147 DNA mismatch repair protein Msh6 Human genes 0.000 description 1
- 102100037799 DNA-binding protein Ikaros Human genes 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 101100503636 Danio rerio fyna gene Proteins 0.000 description 1
- 101100107081 Danio rerio zbtb16a gene Proteins 0.000 description 1
- 241000605716 Desulfovibrio Species 0.000 description 1
- 101100339887 Drosophila melanogaster Hsp27 gene Proteins 0.000 description 1
- 101100300807 Drosophila melanogaster spn-A gene Proteins 0.000 description 1
- 108050002772 E3 ubiquitin-protein ligase Mdm2 Proteins 0.000 description 1
- 102000012199 E3 ubiquitin-protein ligase Mdm2 Human genes 0.000 description 1
- 102100037024 E3 ubiquitin-protein ligase XIAP Human genes 0.000 description 1
- 102000001301 EGF receptor Human genes 0.000 description 1
- 108060006698 EGF receptor Proteins 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 101150004694 Erbb4 gene Proteins 0.000 description 1
- 241000588698 Erwinia Species 0.000 description 1
- 102100031690 Erythroid transcription factor Human genes 0.000 description 1
- 241000588722 Escherichia Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 102100038595 Estrogen receptor Human genes 0.000 description 1
- 101150031329 Ets1 gene Proteins 0.000 description 1
- 108010007457 Extracellular Signal-Regulated MAP Kinases Proteins 0.000 description 1
- 108091008794 FGF receptors Proteins 0.000 description 1
- 101150018272 FYN gene Proteins 0.000 description 1
- 102100023600 Fibroblast growth factor receptor 2 Human genes 0.000 description 1
- 101710182389 Fibroblast growth factor receptor 2 Proteins 0.000 description 1
- 102100027842 Fibroblast growth factor receptor 3 Human genes 0.000 description 1
- 101710182396 Fibroblast growth factor receptor 3 Proteins 0.000 description 1
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
- 102100037813 Focal adhesion kinase 1 Human genes 0.000 description 1
- 108010009306 Forkhead Box Protein O1 Proteins 0.000 description 1
- 102100035427 Forkhead box protein O1 Human genes 0.000 description 1
- 241000605909 Fusobacterium Species 0.000 description 1
- 102000027587 GPCRs class F Human genes 0.000 description 1
- 108091008884 GPCRs class F Proteins 0.000 description 1
- 101150106478 GPS1 gene Proteins 0.000 description 1
- 102100039788 GTPase NRas Human genes 0.000 description 1
- 206010061968 Gastric neoplasm Diseases 0.000 description 1
- 230000010558 Gene Alterations Effects 0.000 description 1
- 241001135750 Geobacter Species 0.000 description 1
- 102100033295 Glial cell line-derived neurotrophic factor Human genes 0.000 description 1
- 108090000079 Glucocorticoid Receptors Proteins 0.000 description 1
- 102000003676 Glucocorticoid Receptors Human genes 0.000 description 1
- 108010091938 HLA-B7 Antigen Proteins 0.000 description 1
- 108700039143 HMGA2 Proteins 0.000 description 1
- 101150096895 HSPB1 gene Proteins 0.000 description 1
- 241000204988 Haloferax mediterranei Species 0.000 description 1
- 102100021866 Hepatocyte growth factor Human genes 0.000 description 1
- 102100022623 Hepatocyte growth factor receptor Human genes 0.000 description 1
- 102100022057 Hepatocyte nuclear factor 1-alpha Human genes 0.000 description 1
- 102100022123 Hepatocyte nuclear factor 1-beta Human genes 0.000 description 1
- 102100031000 Hepatoma-derived growth factor Human genes 0.000 description 1
- 102000005548 Hexokinase Human genes 0.000 description 1
- 102100028999 High mobility group protein HMGI-C Human genes 0.000 description 1
- 108090000353 Histone deacetylase Proteins 0.000 description 1
- 102100038720 Histone deacetylase 9 Human genes 0.000 description 1
- 102100039121 Histone-lysine N-methyltransferase MECOM Human genes 0.000 description 1
- 102100024594 Histone-lysine N-methyltransferase PRDM16 Human genes 0.000 description 1
- 102100032742 Histone-lysine N-methyltransferase SETD2 Human genes 0.000 description 1
- 108010033040 Histones Proteins 0.000 description 1
- 101150073387 Hmga2 gene Proteins 0.000 description 1
- 241001272567 Hominoidea Species 0.000 description 1
- 101000600756 Homo sapiens 3-phosphoinositide-dependent protein kinase 1 Proteins 0.000 description 1
- 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 description 1
- 101000870662 Homo sapiens ATP-dependent RNA helicase DDX3X Proteins 0.000 description 1
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 description 1
- 101000971073 Homo sapiens Bcl-2-like protein 12 Proteins 0.000 description 1
- 101000959437 Homo sapiens Beta-2 adrenergic receptor Proteins 0.000 description 1
- 101000946926 Homo sapiens C-C chemokine receptor type 5 Proteins 0.000 description 1
- 101000897480 Homo sapiens C-C motif chemokine 2 Proteins 0.000 description 1
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 description 1
- 101000945515 Homo sapiens CCAAT/enhancer-binding protein alpha Proteins 0.000 description 1
- 101000777550 Homo sapiens CCN family member 2 Proteins 0.000 description 1
- 101000916173 Homo sapiens Catenin beta-1 Proteins 0.000 description 1
- 101000855516 Homo sapiens Cyclic AMP-responsive element-binding protein 1 Proteins 0.000 description 1
- 101000980932 Homo sapiens Cyclin-dependent kinase inhibitor 2A Proteins 0.000 description 1
- 101000865183 Homo sapiens DEP domain-containing mTOR-interacting protein Proteins 0.000 description 1
- 101001134036 Homo sapiens DNA mismatch repair protein Msh2 Proteins 0.000 description 1
- 101000968658 Homo sapiens DNA mismatch repair protein Msh6 Proteins 0.000 description 1
- 101000599038 Homo sapiens DNA-binding protein Ikaros Proteins 0.000 description 1
- 101001066268 Homo sapiens Erythroid transcription factor Proteins 0.000 description 1
- 101000882584 Homo sapiens Estrogen receptor Proteins 0.000 description 1
- 101000878536 Homo sapiens Focal adhesion kinase 1 Proteins 0.000 description 1
- 101000744505 Homo sapiens GTPase NRas Proteins 0.000 description 1
- 101000898034 Homo sapiens Hepatocyte growth factor Proteins 0.000 description 1
- 101000972946 Homo sapiens Hepatocyte growth factor receptor Proteins 0.000 description 1
- 101001045751 Homo sapiens Hepatocyte nuclear factor 1-alpha Proteins 0.000 description 1
- 101001045758 Homo sapiens Hepatocyte nuclear factor 1-beta Proteins 0.000 description 1
- 101000882127 Homo sapiens Histone-lysine N-methyltransferase EZH2 Proteins 0.000 description 1
- 101001033728 Homo sapiens Histone-lysine N-methyltransferase MECOM Proteins 0.000 description 1
- 101000686942 Homo sapiens Histone-lysine N-methyltransferase PRDM16 Proteins 0.000 description 1
- 101000654725 Homo sapiens Histone-lysine N-methyltransferase SETD2 Proteins 0.000 description 1
- 101001056180 Homo sapiens Induced myeloid leukemia cell differentiation protein Mcl-1 Proteins 0.000 description 1
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 1
- 101000598002 Homo sapiens Interferon regulatory factor 1 Proteins 0.000 description 1
- 101001011441 Homo sapiens Interferon regulatory factor 4 Proteins 0.000 description 1
- 101001002634 Homo sapiens Interleukin-1 alpha Proteins 0.000 description 1
- 101001076408 Homo sapiens Interleukin-6 Proteins 0.000 description 1
- 101001139126 Homo sapiens Krueppel-like factor 6 Proteins 0.000 description 1
- 101001043352 Homo sapiens Lysyl oxidase homolog 2 Proteins 0.000 description 1
- 101000954986 Homo sapiens Merlin Proteins 0.000 description 1
- 101000669513 Homo sapiens Metalloproteinase inhibitor 1 Proteins 0.000 description 1
- 101000835893 Homo sapiens Mothers against decapentaplegic homolog 4 Proteins 0.000 description 1
- 101001124388 Homo sapiens NPC intracellular cholesterol transporter 1 Proteins 0.000 description 1
- 101000970023 Homo sapiens NUAK family SNF1-like kinase 1 Proteins 0.000 description 1
- 101000581981 Homo sapiens Neural cell adhesion molecule 1 Proteins 0.000 description 1
- 101001109689 Homo sapiens Nuclear receptor subfamily 4 group A member 3 Proteins 0.000 description 1
- 101000613490 Homo sapiens Paired box protein Pax-3 Proteins 0.000 description 1
- 101000601724 Homo sapiens Paired box protein Pax-5 Proteins 0.000 description 1
- 101000601661 Homo sapiens Paired box protein Pax-7 Proteins 0.000 description 1
- 101000692768 Homo sapiens Paired mesoderm homeobox protein 2B Proteins 0.000 description 1
- 101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 description 1
- 101000610107 Homo sapiens Pre-B-cell leukemia transcription factor 1 Proteins 0.000 description 1
- 101000611943 Homo sapiens Programmed cell death protein 4 Proteins 0.000 description 1
- 101000690268 Homo sapiens Proline-rich AKT1 substrate 1 Proteins 0.000 description 1
- 101000928034 Homo sapiens Proteasomal ubiquitin receptor ADRM1 Proteins 0.000 description 1
- 101001136986 Homo sapiens Proteasome subunit beta type-8 Proteins 0.000 description 1
- 101001136981 Homo sapiens Proteasome subunit beta type-9 Proteins 0.000 description 1
- 101000573199 Homo sapiens Protein PML Proteins 0.000 description 1
- 101000958299 Homo sapiens Protein lyl-1 Proteins 0.000 description 1
- 101000579425 Homo sapiens Proto-oncogene tyrosine-protein kinase receptor Ret Proteins 0.000 description 1
- 101000687474 Homo sapiens Rhombotin-1 Proteins 0.000 description 1
- 101000575639 Homo sapiens Ribonucleoside-diphosphate reductase subunit M2 Proteins 0.000 description 1
- 101000654718 Homo sapiens SET-binding protein Proteins 0.000 description 1
- 101000984753 Homo sapiens Serine/threonine-protein kinase B-raf Proteins 0.000 description 1
- 101000691455 Homo sapiens Serine/threonine-protein kinase N3 Proteins 0.000 description 1
- 101000836383 Homo sapiens Serpin H1 Proteins 0.000 description 1
- 101000868152 Homo sapiens Son of sevenless homolog 1 Proteins 0.000 description 1
- 101000617830 Homo sapiens Sterol O-acyltransferase 1 Proteins 0.000 description 1
- 101000874179 Homo sapiens Syndecan-1 Proteins 0.000 description 1
- 101000891113 Homo sapiens T-cell acute lymphocytic leukemia protein 1 Proteins 0.000 description 1
- 101000819111 Homo sapiens Trans-acting T-cell-specific transcription factor GATA-3 Proteins 0.000 description 1
- 101001050288 Homo sapiens Transcription factor Jun Proteins 0.000 description 1
- 101000711846 Homo sapiens Transcription factor SOX-9 Proteins 0.000 description 1
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 description 1
- 101000733249 Homo sapiens Tumor suppressor ARF Proteins 0.000 description 1
- 101000864342 Homo sapiens Tyrosine-protein kinase BTK Proteins 0.000 description 1
- 101000851018 Homo sapiens Vascular endothelial growth factor receptor 1 Proteins 0.000 description 1
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 1
- 101000851030 Homo sapiens Vascular endothelial growth factor receptor 3 Proteins 0.000 description 1
- 101000666295 Homo sapiens X-box-binding protein 1 Proteins 0.000 description 1
- 101100377226 Homo sapiens ZBTB16 gene Proteins 0.000 description 1
- 101001117146 Homo sapiens [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial Proteins 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- 101150104906 Idh2 gene Proteins 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 102100026539 Induced myeloid leukemia cell differentiation protein Mcl-1 Human genes 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 1
- 229930010555 Inosine Natural products 0.000 description 1
- 102100036981 Interferon regulatory factor 1 Human genes 0.000 description 1
- 102100030126 Interferon regulatory factor 4 Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 102100020881 Interleukin-1 alpha Human genes 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- 102000042838 JAK family Human genes 0.000 description 1
- 108091082332 JAK family Proteins 0.000 description 1
- 108010055717 JNK Mitogen-Activated Protein Kinases Proteins 0.000 description 1
- 102000019145 JUN kinase activity proteins Human genes 0.000 description 1
- 102100040441 Keratin, type I cytoskeletal 16 Human genes 0.000 description 1
- 102100033511 Keratin, type I cytoskeletal 17 Human genes 0.000 description 1
- 102100025655 Keratin, type II cytoskeletal 6B Human genes 0.000 description 1
- 101710083640 Keratin, type II cytoskeletal 6B Proteins 0.000 description 1
- 108010066364 Keratin-16 Proteins 0.000 description 1
- 108010066325 Keratin-17 Proteins 0.000 description 1
- 101710172072 Kexin Proteins 0.000 description 1
- 102100020679 Krueppel-like factor 6 Human genes 0.000 description 1
- 241001112693 Lachnospiraceae Species 0.000 description 1
- 101710128836 Large T antigen Proteins 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- 241000589248 Legionella Species 0.000 description 1
- 208000007764 Legionnaires' Disease Diseases 0.000 description 1
- 108010013563 Lipoprotein Lipase Proteins 0.000 description 1
- 102100022119 Lipoprotein lipase Human genes 0.000 description 1
- 241000186781 Listeria Species 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 102100021948 Lysyl oxidase homolog 2 Human genes 0.000 description 1
- 102000001291 MAP Kinase Kinase Kinase Human genes 0.000 description 1
- 102000043136 MAP kinase family Human genes 0.000 description 1
- 108091054455 MAP kinase family Proteins 0.000 description 1
- 108060006687 MAP kinase kinase kinase Proteins 0.000 description 1
- 108010018650 MEF2 Transcription Factors Proteins 0.000 description 1
- 101150088406 MLST8 gene Proteins 0.000 description 1
- 108010047702 MPG peptide Proteins 0.000 description 1
- 229910015837 MSH2 Inorganic materials 0.000 description 1
- 101150112867 MX1 gene Proteins 0.000 description 1
- 102100030412 Matrix metalloproteinase-9 Human genes 0.000 description 1
- 108010015302 Matrix metalloproteinase-9 Proteins 0.000 description 1
- 102100037106 Merlin Human genes 0.000 description 1
- 102100039364 Metalloproteinase inhibitor 1 Human genes 0.000 description 1
- 241000202974 Methanobacterium Species 0.000 description 1
- 241000203353 Methanococcus Species 0.000 description 1
- 241000204675 Methanopyrus Species 0.000 description 1
- 241000205276 Methanosarcina Species 0.000 description 1
- 241000589345 Methylococcus Species 0.000 description 1
- 102000004232 Mitogen-Activated Protein Kinase Kinases Human genes 0.000 description 1
- 108090000744 Mitogen-Activated Protein Kinase Kinases Proteins 0.000 description 1
- 102100025751 Mothers against decapentaplegic homolog 2 Human genes 0.000 description 1
- 102100025725 Mothers against decapentaplegic homolog 4 Human genes 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 102000007474 Multiprotein Complexes Human genes 0.000 description 1
- 108010085220 Multiprotein Complexes Proteins 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 101100381525 Mus musculus Bcl6 gene Proteins 0.000 description 1
- 101100219625 Mus musculus Casd1 gene Proteins 0.000 description 1
- 101100078999 Mus musculus Mx1 gene Proteins 0.000 description 1
- 101100135848 Mus musculus Pcsk9 gene Proteins 0.000 description 1
- 101001098862 Mus musculus Proprotein convertase subtilisin/kexin type 9 Proteins 0.000 description 1
- 101100087591 Mus musculus Rictor gene Proteins 0.000 description 1
- 101100365690 Mus musculus Shc1 gene Proteins 0.000 description 1
- 108010026664 MutL Protein Homolog 1 Proteins 0.000 description 1
- 241000186359 Mycobacterium Species 0.000 description 1
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 1
- 101000619903 Mycolicibacterium smegmatis L-lactate 2-monooxygenase Proteins 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- 102100039229 Myocyte-specific enhancer factor 2C Human genes 0.000 description 1
- 101001055320 Myxine glutinosa Insulin-like growth factor Proteins 0.000 description 1
- 241000863420 Myxococcus Species 0.000 description 1
- 108010057466 NF-kappa B Proteins 0.000 description 1
- 102000003945 NF-kappa B Human genes 0.000 description 1
- 108010018525 NFATC Transcription Factors Proteins 0.000 description 1
- 102000002673 NFATC Transcription Factors Human genes 0.000 description 1
- 102100029565 NPC intracellular cholesterol transporter 1 Human genes 0.000 description 1
- 102100021732 NUAK family SNF1-like kinase 1 Human genes 0.000 description 1
- 241000169176 Natronobacterium gregoryi Species 0.000 description 1
- 241000588653 Neisseria Species 0.000 description 1
- 102100027347 Neural cell adhesion molecule 1 Human genes 0.000 description 1
- 102000007530 Neurofibromin 1 Human genes 0.000 description 1
- 108010085793 Neurofibromin 1 Proteins 0.000 description 1
- 101100385413 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) csm-3 gene Proteins 0.000 description 1
- 241000605122 Nitrosomonas Species 0.000 description 1
- 108010029755 Notch1 Receptor Proteins 0.000 description 1
- 102000001759 Notch1 Receptor Human genes 0.000 description 1
- 102100022673 Nuclear receptor subfamily 4 group A member 3 Human genes 0.000 description 1
- 108091005461 Nucleic proteins Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 101000840556 Oryza sativa subsp. japonica Hexokinase-4, chloroplastic Proteins 0.000 description 1
- 102000004264 Osteopontin Human genes 0.000 description 1
- 108010081689 Osteopontin Proteins 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 108091007960 PI3Ks Proteins 0.000 description 1
- 102000038030 PI3Ks Human genes 0.000 description 1
- 101150021069 PRDX2 gene Proteins 0.000 description 1
- 102100040891 Paired box protein Pax-3 Human genes 0.000 description 1
- 102100037504 Paired box protein Pax-5 Human genes 0.000 description 1
- 102100037503 Paired box protein Pax-7 Human genes 0.000 description 1
- 102100026354 Paired mesoderm homeobox protein 2B Human genes 0.000 description 1
- 241000606860 Pasteurella Species 0.000 description 1
- 108010069873 Patched Receptors Proteins 0.000 description 1
- 102000000017 Patched Receptors Human genes 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 241000607568 Photobacterium Species 0.000 description 1
- 241000204826 Picrophilus Species 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 108010022233 Plasminogen Activator Inhibitor 1 Proteins 0.000 description 1
- 102100039418 Plasminogen activator inhibitor 1 Human genes 0.000 description 1
- 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 description 1
- 108010064218 Poly (ADP-Ribose) Polymerase-1 Proteins 0.000 description 1
- 102100023712 Poly [ADP-ribose] polymerase 1 Human genes 0.000 description 1
- 102000012338 Poly(ADP-ribose) Polymerases Human genes 0.000 description 1
- 108010061844 Poly(ADP-ribose) Polymerases Proteins 0.000 description 1
- 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 description 1
- 229920002873 Polyethylenimine Polymers 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 241000605894 Porphyromonas Species 0.000 description 1
- 101150076311 Prdx1 gene Proteins 0.000 description 1
- 102100040171 Pre-B-cell leukemia transcription factor 1 Human genes 0.000 description 1
- 108010071690 Prealbumin Proteins 0.000 description 1
- 102100033237 Pro-epidermal growth factor Human genes 0.000 description 1
- 101710098940 Pro-epidermal growth factor Proteins 0.000 description 1
- 102100040992 Programmed cell death protein 4 Human genes 0.000 description 1
- 102100024091 Proline-rich AKT1 substrate 1 Human genes 0.000 description 1
- 108700003766 Promyelocytic Leukemia Zinc Finger Proteins 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 102100036915 Proteasomal ubiquitin receptor ADRM1 Human genes 0.000 description 1
- 102100035760 Proteasome subunit beta type-8 Human genes 0.000 description 1
- 102100035764 Proteasome subunit beta type-9 Human genes 0.000 description 1
- 108091008611 Protein Kinase B Proteins 0.000 description 1
- 102000003923 Protein Kinase C Human genes 0.000 description 1
- 108090000315 Protein Kinase C Proteins 0.000 description 1
- 102100026375 Protein PML Human genes 0.000 description 1
- 102100038231 Protein lyl-1 Human genes 0.000 description 1
- 101710082106 Protein sprouty homolog 2 Proteins 0.000 description 1
- 102100030400 Protein sprouty homolog 2 Human genes 0.000 description 1
- 101150094745 Ptk2b gene Proteins 0.000 description 1
- 241000205226 Pyrobaculum Species 0.000 description 1
- 241000205160 Pyrococcus Species 0.000 description 1
- 102000004229 RNA-binding protein EWS Human genes 0.000 description 1
- 108090000740 RNA-binding protein EWS Proteins 0.000 description 1
- 108091030071 RNAI Proteins 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 101100047461 Rattus norvegicus Trpm8 gene Proteins 0.000 description 1
- 108010029031 Regulatory-Associated Protein of mTOR Proteins 0.000 description 1
- 108091081062 Repeated sequence (DNA) Proteins 0.000 description 1
- 102100024869 Rhombotin-1 Human genes 0.000 description 1
- 102100026006 Ribonucleoside-diphosphate reductase subunit M2 Human genes 0.000 description 1
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
- 108010034782 Ribosomal Protein S6 Kinases Proteins 0.000 description 1
- 102000009738 Ribosomal Protein S6 Kinases Human genes 0.000 description 1
- 102100025373 Runt-related transcription factor 1 Human genes 0.000 description 1
- 102100032741 SET-binding protein Human genes 0.000 description 1
- 101150063267 STAT5B gene Proteins 0.000 description 1
- 101000744436 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) Trans-acting factor D Proteins 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 101000702553 Schistosoma mansoni Antigen Sm21.7 Proteins 0.000 description 1
- 101000714192 Schistosoma mansoni Tegument antigen Proteins 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Chemical group OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 102100027103 Serine/threonine-protein kinase B-raf Human genes 0.000 description 1
- 102100026219 Serine/threonine-protein kinase N3 Human genes 0.000 description 1
- 102100031463 Serine/threonine-protein kinase PLK1 Human genes 0.000 description 1
- 101710183160 Serine/threonine-protein kinase PLK1 Proteins 0.000 description 1
- 102100027287 Serpin H1 Human genes 0.000 description 1
- 102100024474 Signal transducer and activator of transcription 5B Human genes 0.000 description 1
- 108700032504 Smad2 Proteins 0.000 description 1
- 101150102611 Smad2 gene Proteins 0.000 description 1
- 108091027967 Small hairpin RNA Proteins 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 102100021993 Sterol O-acyltransferase 1 Human genes 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- 101000697584 Streptomyces lavendulae Streptothricin acetyltransferase Proteins 0.000 description 1
- 102100029540 Structural maintenance of chromosomes protein 2 Human genes 0.000 description 1
- 101710117946 Structural maintenance of chromosomes protein 2 Proteins 0.000 description 1
- 102100022842 Structural maintenance of chromosomes protein 4 Human genes 0.000 description 1
- 101710117916 Structural maintenance of chromosomes protein 4 Proteins 0.000 description 1
- 108090000787 Subtilisin Proteins 0.000 description 1
- 241000205101 Sulfolobus Species 0.000 description 1
- 108010002687 Survivin Proteins 0.000 description 1
- 102100035721 Syndecan-1 Human genes 0.000 description 1
- 102100040365 T-cell acute lymphocytic leukemia protein 1 Human genes 0.000 description 1
- 238000012245 TALEN-based genome engineering Methods 0.000 description 1
- 108091005735 TGF-beta receptors Proteins 0.000 description 1
- 102000003566 TRPV1 Human genes 0.000 description 1
- 102100027802 Target of rapamycin complex subunit LST8 Human genes 0.000 description 1
- 241000186339 Thermoanaerobacter Species 0.000 description 1
- 241000204667 Thermoplasma Species 0.000 description 1
- 241000204652 Thermotoga Species 0.000 description 1
- 241000589596 Thermus Species 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 1
- 108060008245 Thrombospondin Proteins 0.000 description 1
- 102000002938 Thrombospondin Human genes 0.000 description 1
- 102000006601 Thymidine Kinase Human genes 0.000 description 1
- 108020004440 Thymidine kinase Proteins 0.000 description 1
- 241000283907 Tragelaphus oryx Species 0.000 description 1
- 102100021386 Trans-acting T-cell-specific transcription factor GATA-3 Human genes 0.000 description 1
- 102100023132 Transcription factor Jun Human genes 0.000 description 1
- 102100034204 Transcription factor SOX-9 Human genes 0.000 description 1
- 102000016715 Transforming Growth Factor beta Receptors Human genes 0.000 description 1
- 102000009190 Transthyretin Human genes 0.000 description 1
- 241000589886 Treponema Species 0.000 description 1
- 101150016206 Trpv1 gene Proteins 0.000 description 1
- 108010078814 Tumor Suppressor Protein p53 Proteins 0.000 description 1
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 description 1
- 102100039094 Tyrosinase Human genes 0.000 description 1
- 108060008724 Tyrosinase Proteins 0.000 description 1
- 102100029823 Tyrosine-protein kinase BTK Human genes 0.000 description 1
- 102000006275 Ubiquitin-Protein Ligases Human genes 0.000 description 1
- 108010083111 Ubiquitin-Protein Ligases Proteins 0.000 description 1
- 101150010086 VP24 gene Proteins 0.000 description 1
- 101150026858 VP30 gene Proteins 0.000 description 1
- 101150077651 VP35 gene Proteins 0.000 description 1
- 101150036892 VP40 gene Proteins 0.000 description 1
- 102100033178 Vascular endothelial growth factor receptor 1 Human genes 0.000 description 1
- 102100033179 Vascular endothelial growth factor receptor 3 Human genes 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 108700020467 WT1 Proteins 0.000 description 1
- 101150084041 WT1 gene Proteins 0.000 description 1
- 102100022748 Wilms tumor protein Human genes 0.000 description 1
- 108050003627 Wnt Proteins 0.000 description 1
- 241000605941 Wolinella Species 0.000 description 1
- 108700031544 X-Linked Inhibitor of Apoptosis Proteins 0.000 description 1
- 102100038151 X-box-binding protein 1 Human genes 0.000 description 1
- 241000589634 Xanthomonas Species 0.000 description 1
- 241000607734 Yersinia <bacteria> Species 0.000 description 1
- 108010016200 Zinc Finger Protein GLI1 Proteins 0.000 description 1
- 102100040314 Zinc finger and BTB domain-containing protein 16 Human genes 0.000 description 1
- 102100035535 Zinc finger protein GLI1 Human genes 0.000 description 1
- 102100025093 Zinc fingers and homeoboxes protein 2 Human genes 0.000 description 1
- 102100024148 [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial Human genes 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 102000030621 adenylate cyclase Human genes 0.000 description 1
- 108060000200 adenylate cyclase Proteins 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 102000009899 alpha Karyopherins Human genes 0.000 description 1
- 108010077099 alpha Karyopherins Proteins 0.000 description 1
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
- 108010026331 alpha-Fetoproteins Proteins 0.000 description 1
- 102000013529 alpha-Fetoproteins Human genes 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000002491 angiogenic effect Effects 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 235000009697 arginine Nutrition 0.000 description 1
- 150000001484 arginines Chemical class 0.000 description 1
- 210000004507 artificial chromosome Anatomy 0.000 description 1
- 108010006523 asialoglycoprotein receptor Proteins 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 229940000635 beta-alanine Drugs 0.000 description 1
- 229960000397 bevacizumab Drugs 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 101150038500 cas9 gene Proteins 0.000 description 1
- 101150055766 cat gene Proteins 0.000 description 1
- 108020001778 catalytic domains Proteins 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 210000003763 chloroplast Anatomy 0.000 description 1
- 239000013611 chromosomal DNA Substances 0.000 description 1
- 230000000536 complexating effect Effects 0.000 description 1
- 108091036078 conserved sequence Proteins 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 101150055601 cops2 gene Proteins 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 229940124447 delivery agent Drugs 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000005782 double-strand break Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 229960004137 elotuzumab Drugs 0.000 description 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
- 230000001973 epigenetic effect Effects 0.000 description 1
- 108010085279 eukaryotic translation initiation factor 5A Proteins 0.000 description 1
- 102000052178 fibroblast growth factor receptor activity proteins Human genes 0.000 description 1
- 238000002073 fluorescence micrograph Methods 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 125000002519 galactosyl group Chemical group C1([C@H](O)[C@@H](O)[C@@H](O)[C@H](O1)CO)* 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000001476 gene delivery Methods 0.000 description 1
- 238000012239 gene modification Methods 0.000 description 1
- 230000009368 gene silencing by RNA Effects 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 108010052188 hepatoma-derived growth factor Proteins 0.000 description 1
- 238000002744 homologous recombination Methods 0.000 description 1
- 230000006801 homologous recombination Effects 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 102000048160 human CCR5 Human genes 0.000 description 1
- 101150046722 idh1 gene Proteins 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 108700032552 influenza virus INS1 Proteins 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229960003786 inosine Drugs 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 229960003130 interferon gamma Drugs 0.000 description 1
- 108090000237 interleukin-24 Proteins 0.000 description 1
- 102000003898 interleukin-24 Human genes 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000000185 intracerebroventricular administration Methods 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 230000002601 intratumoral effect Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 238000011005 laboratory method Methods 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 201000010260 leiomyoma Diseases 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 201000005296 lung carcinoma Diseases 0.000 description 1
- 208000019420 lymphoid neoplasm Diseases 0.000 description 1
- 235000018977 lysine Nutrition 0.000 description 1
- 150000002669 lysines Chemical class 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000013011 mating Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 208000024191 minimally invasive lung adenocarcinoma Diseases 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000030648 nucleus localization Effects 0.000 description 1
- 210000003463 organelle Anatomy 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- LQRJAEQXMSMEDP-XCHBZYMASA-N peptide a Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](C)C(=O)NCCCC[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)C(\NC(=O)[C@@H](CCCCN)NC(=O)CNC(C)=O)=C/C=1C=CC=CC=1)C(N)=O)C(=O)C(\NC(=O)[C@@H](CCCCN)NC(=O)CNC(C)=O)=C\C1=CC=CC=C1 LQRJAEQXMSMEDP-XCHBZYMASA-N 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 1
- PTMHPRAIXMAOOB-UHFFFAOYSA-N phosphoramidic acid Chemical class NP(O)(O)=O PTMHPRAIXMAOOB-UHFFFAOYSA-N 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 1
- 229920000139 polyethylene terephthalate Polymers 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 230000023603 positive regulation of transcription initiation, DNA-dependent Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 208000023958 prostate neoplasm Diseases 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000018975 regulation of cholesterol transport Effects 0.000 description 1
- 230000018406 regulation of metabolic process Effects 0.000 description 1
- 230000024769 regulation of transport Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000000754 repressing effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 101150012554 shc gene Proteins 0.000 description 1
- 239000004055 small Interfering RNA Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 102000005969 steroid hormone receptors Human genes 0.000 description 1
- 108020003113 steroid hormone receptors Proteins 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- 102000009816 urokinase plasminogen activator receptor activity proteins Human genes 0.000 description 1
- 108040001269 urokinase plasminogen activator receptor activity proteins Proteins 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000013603 viral vector Substances 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
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 208000006542 von Hippel-Lindau disease Diseases 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/465—Hydrolases (3) acting on ester bonds (3.1), e.g. lipases, ribonucleases
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/10—Cellular immunotherapy characterised by the cell type used
- A61K40/11—T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/30—Cellular immunotherapy characterised by the recombinant expression of specific molecules in the cells of the immune system
- A61K40/31—Chimeric antigen receptors [CAR]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
- A61K40/41—Vertebrate antigens
- A61K40/42—Cancer antigens
- A61K40/4202—Receptors, cell surface antigens or cell surface determinants
- A61K40/421—Immunoglobulin superfamily
- A61K40/4211—CD19 or B4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/111—General methods applicable to biologically active non-coding nucleic acids
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
- C12N15/90—Stable introduction of foreign DNA into chromosome
- C12N15/902—Stable introduction of foreign DNA into chromosome using homologous recombination
- C12N15/907—Stable introduction of foreign DNA into chromosome using homologous recombination in mammalian cells
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
- C12N9/22—Ribonucleases [RNase]; Deoxyribonucleases [DNase]
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/7051—T-cell receptor (TcR)-CD3 complex
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/03—Fusion polypeptide containing a localisation/targetting motif containing a transmembrane segment
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/09—Fusion polypeptide containing a localisation/targetting motif containing a nuclear localisation signal
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/10—Fusion polypeptide containing a localisation/targetting motif containing a tag for extracellular membrane crossing, e.g. TAT or VP22
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/20—Type of nucleic acid involving clustered regularly interspaced short palindromic repeats [CRISPR]
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2320/00—Applications; Uses
- C12N2320/30—Special therapeutic applications
- C12N2320/32—Special delivery means, e.g. tissue-specific
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Pharmacology & Pharmacy (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Diabetes (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Immunology (AREA)
- Oncology (AREA)
- Mycology (AREA)
- Nanotechnology (AREA)
- Hematology (AREA)
- Gastroenterology & Hepatology (AREA)
- Obesity (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Ophthalmology & Optometry (AREA)
- Medical Informatics (AREA)
- Rheumatology (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662342823P | 2016-05-27 | 2016-05-27 | |
| US201662394140P | 2016-09-13 | 2016-09-13 | |
| US201762477357P | 2017-03-27 | 2017-03-27 | |
| PCT/US2017/034862 WO2017205846A1 (en) | 2016-05-27 | 2017-05-26 | Peptides and nanoparticles for intracellular delivery of genome-editing molecules |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2901215T3 true ES2901215T3 (es) | 2022-03-21 |
Family
ID=59239942
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES17733918T Active ES2901215T3 (es) | 2016-05-27 | 2017-05-26 | Péptidos y nanopartículas para la liberación intracelular de moléculas de edición del genoma |
Country Status (9)
| Country | Link |
|---|---|
| EP (2) | EP3464323B1 (enExample) |
| JP (4) | JP2019521659A (enExample) |
| CN (2) | CN117431234A (enExample) |
| AU (2) | AU2017268842B2 (enExample) |
| CA (1) | CA3025523A1 (enExample) |
| ES (1) | ES2901215T3 (enExample) |
| MX (2) | MX388294B (enExample) |
| WO (1) | WO2017205846A1 (enExample) |
| ZA (1) | ZA201807869B (enExample) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2020530463A (ja) * | 2017-08-10 | 2020-10-22 | アーディジェン， エルエルシー | ウイルスの細胞内送達のためのペプチドおよびナノ粒子 |
| WO2019079215A1 (en) * | 2017-10-16 | 2019-04-25 | Aadigen, Llc | PEPTIDES AND NANOPARTICLES FOR INTRACELLULAR MRRNA DELIVERY |
| FR3081169B1 (fr) * | 2018-05-15 | 2020-06-19 | Messenger Biopharma | Substitution de la coiffe des arn messagers par deux sequences d'arn introduites a leur extremite 5' |
| WO2019237387A1 (zh) * | 2018-06-16 | 2019-12-19 | 深圳市博奥康生物科技有限公司 | 用于敲除人ACT35基因的gRNA序列及其应用 |
| WO2019237384A1 (zh) * | 2018-06-16 | 2019-12-19 | 深圳市博奥康生物科技有限公司 | 用于敲除人CDw137基因的gRNA序列及其应用 |
| CN111363013B (zh) * | 2018-12-25 | 2021-11-19 | 深圳先进技术研究院 | 多组分纳米颗粒簇的构建方法 |
| GB201902648D0 (en) | 2019-02-27 | 2019-04-10 | Cyca Oncosolutions Ltd | Cell membrane penetrating conjugates |
| CN114007654A (zh) * | 2019-04-17 | 2022-02-01 | 阿迪根有限公司 | 用于分子的细胞内递送的肽和纳米颗粒 |
| CN109880891B (zh) * | 2019-04-22 | 2021-07-30 | 上海交通大学 | 基于核酸酶偶联pcr原理富集低丰度dna突变的检测技术体系及应用 |
| CN120022385A (zh) * | 2019-05-07 | 2025-05-23 | 洛桑联邦理工学院 | Fmrp及癌症治疗 |
| CN110638789A (zh) * | 2019-10-31 | 2020-01-03 | 南开大学 | 一种可实现肿瘤靶向递送核糖核蛋白复合物的纳米粒子的制备方法和应用 |
| US20230167437A1 (en) * | 2020-04-24 | 2023-06-01 | Aadigen, Llc | Compositions for treating cancer with kras mutations and uses thereof |
| EP4185602A1 (en) * | 2020-07-24 | 2023-05-31 | Aadigen, LLC | Compositions and methods for treating viral infections |
| KR102500873B1 (ko) * | 2021-02-03 | 2023-02-17 | 한국과학기술연구원 | 자연살해세포 특이적 CRISPR/Cas 시스템을 위한 융합 단백질 및 이의 용도 |
| EP4377472A2 (en) * | 2021-07-26 | 2024-06-05 | Imperial College Innovations Limited | Nanozyme-catalysed detection of nucleic acids |
| WO2025059215A1 (en) | 2023-09-12 | 2025-03-20 | Aadigen, Llc | Methods and compositions for treating or preventing cancer |
| WO2025090926A1 (en) * | 2023-10-26 | 2025-05-01 | The Penn State Research Foundation | Ultrasound-sensitive peptide particles with surface-bound gene editing tools for spatially resolved molecule delivery |
| CN119119204B (zh) * | 2024-11-11 | 2025-03-18 | 南昌大学 | 温敏特异性多肽和基于温差特异性无损分离外泌体的方法 |
Family Cites Families (59)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5356802A (en) | 1992-04-03 | 1994-10-18 | The Johns Hopkins University | Functional domains in flavobacterium okeanokoites (FokI) restriction endonuclease |
| US5436150A (en) | 1992-04-03 | 1995-07-25 | The Johns Hopkins University | Functional domains in flavobacterium okeanokoities (foki) restriction endonuclease |
| US5487994A (en) | 1992-04-03 | 1996-01-30 | The Johns Hopkins University | Insertion and deletion mutants of FokI restriction endonuclease |
| AU5600194A (en) | 1992-11-13 | 1994-06-08 | Winalee G. Mitchell | Absorbent including super absorbent and capacity monitor |
| WO1996040958A1 (en) | 1995-06-07 | 1996-12-19 | Baylor College Of Medicine | Nucleic acid transporters for delivery of nucleic acids into a cell |
| US6451995B1 (en) | 1996-03-20 | 2002-09-17 | Sloan-Kettering Institute For Cancer Research | Single chain FV polynucleotide or peptide constructs of anti-ganglioside GD2 antibodies, cells expressing same and related methods |
| WO2000014257A1 (en) | 1998-09-04 | 2000-03-16 | Sloan-Kettering Institute For Cancer Research | Fusion receptors specific for prostate-specific membrane antigen and uses thereof |
| AU2472400A (en) | 1998-10-20 | 2000-05-08 | City Of Hope | CD20-specific redirected T cells and their use in cellular immunotherapy of CD20+ malignancies |
| US6534261B1 (en) | 1999-01-12 | 2003-03-18 | Sangamo Biosciences, Inc. | Regulation of endogenous gene expression in cells using zinc finger proteins |
| US6599692B1 (en) | 1999-09-14 | 2003-07-29 | Sangamo Bioscience, Inc. | Functional genomics using zinc finger proteins |
| US6453242B1 (en) | 1999-01-12 | 2002-09-17 | Sangamo Biosciences, Inc. | Selection of sites for targeting by zinc finger proteins and methods of designing zinc finger proteins to bind to preselected sites |
| US7070934B2 (en) | 1999-01-12 | 2006-07-04 | Sangamo Biosciences, Inc. | Ligand-controlled regulation of endogenous gene expression |
| US7030215B2 (en) | 1999-03-24 | 2006-04-18 | Sangamo Biosciences, Inc. | Position dependent recognition of GNN nucleotide triplets by zinc fingers |
| US6794136B1 (en) | 2000-11-20 | 2004-09-21 | Sangamo Biosciences, Inc. | Iterative optimization in the design of binding proteins |
| AU776576B2 (en) | 1999-12-06 | 2004-09-16 | Sangamo Biosciences, Inc. | Methods of using randomized libraries of zinc finger proteins for the identification of gene function |
| KR20020086508A (ko) | 2000-02-08 | 2002-11-18 | 상가모 바이오사이언스 인코포레이티드 | 약물 발견용 세포 |
| WO2001094944A2 (en) | 2000-06-02 | 2001-12-13 | Memorial Sloan-Kettering Cancer Center | Artificial antigen presenting cells and methods of use thereof |
| JP5312721B2 (ja) | 2000-11-07 | 2013-10-09 | シティ・オブ・ホープ | Ｃｄ１９特異的再指向免疫細胞 |
| US7067317B2 (en) | 2000-12-07 | 2006-06-27 | Sangamo Biosciences, Inc. | Regulation of angiogenesis with zinc finger proteins |
| US7070995B2 (en) | 2001-04-11 | 2006-07-04 | City Of Hope | CE7-specific redirected immune cells |
| US20090257994A1 (en) | 2001-04-30 | 2009-10-15 | City Of Hope | Chimeric immunoreceptor useful in treating human cancers |
| US7262054B2 (en) | 2002-01-22 | 2007-08-28 | Sangamo Biosciences, Inc. | Zinc finger proteins for DNA binding and gene regulation in plants |
| US7446190B2 (en) | 2002-05-28 | 2008-11-04 | Sloan-Kettering Institute For Cancer Research | Nucleic acids encoding chimeric T cell receptors |
| US7361635B2 (en) | 2002-08-29 | 2008-04-22 | Sangamo Biosciences, Inc. | Simultaneous modulation of multiple genes |
| US20050129671A1 (en) | 2003-03-11 | 2005-06-16 | City Of Hope | Mammalian antigen-presenting T cells and bi-specific T cells |
| US7888121B2 (en) | 2003-08-08 | 2011-02-15 | Sangamo Biosciences, Inc. | Methods and compositions for targeted cleavage and recombination |
| US7972854B2 (en) | 2004-02-05 | 2011-07-05 | Sangamo Biosciences, Inc. | Methods and compositions for targeted cleavage and recombination |
| CA2562193A1 (en) | 2004-04-08 | 2005-10-27 | Sangamo Biosciences, Inc. | Treatment of neuropathic pain with zinc finger proteins |
| WO2005099771A2 (en) | 2004-04-08 | 2005-10-27 | Sangamo Biosciences, Inc. | Methods and compositions for treating neuropathic and neurodegenerative conditions |
| US7514530B2 (en) | 2004-04-26 | 2009-04-07 | Centre National De La Recherche Scientifique | Peptide carrier for delivering siRNA into mammalian cells |
| US7579318B2 (en) | 2005-12-06 | 2009-08-25 | Centre De La Recherche De La Scientifique | Cell penetrating peptides for intracellular delivery of molecules |
| JP5840837B2 (ja) | 2007-03-30 | 2016-01-06 | メモリアル スローン−ケタリング キャンサー センター | 養子移入ｔリンパ球における副刺激リガンドの構成性発現 |
| US8479118B2 (en) | 2007-12-10 | 2013-07-02 | Microsoft Corporation | Switching search providers within a browser search box |
| JP5173594B2 (ja) | 2008-05-27 | 2013-04-03 | キヤノン株式会社 | 管理装置、画像形成装置及びそれらの処理方法 |
| DE102008036364A1 (de) | 2008-08-05 | 2010-02-18 | Khs Ag | Verfahren zum Herstellen von Behälterzellen |
| EP2281579A1 (en) | 2009-08-05 | 2011-02-09 | BioNTech AG | Vaccine composition comprising 5'-Cap modified RNA |
| US8889394B2 (en) | 2009-09-07 | 2014-11-18 | Empire Technology Development Llc | Multiple domain proteins |
| EP2571512B1 (en) | 2010-05-17 | 2017-08-23 | Sangamo BioSciences, Inc. | Novel dna-binding proteins and uses thereof |
| PH12013501201A1 (en) | 2010-12-09 | 2013-07-29 | Univ Pennsylvania | Use of chimeric antigen receptor-modified t cells to treat cancer |
| MX359513B (es) | 2011-03-23 | 2018-10-01 | Hutchinson Fred Cancer Res | Metodo y composiciones para inmunoterapia celular. |
| WO2012137036A1 (en) | 2011-04-04 | 2012-10-11 | Centre National De La Recherche Scientifique | Cell penetrating peptides for intracellular delivery of molecules |
| US8398282B2 (en) | 2011-05-12 | 2013-03-19 | Delphi Technologies, Inc. | Vehicle front lighting assembly and systems having a variable tint electrowetting element |
| EP2776451B1 (en) | 2011-11-11 | 2018-07-18 | Fred Hutchinson Cancer Research Center | Cyclin a1-targeted t-cell immunotherapy for cancer |
| EP2814846B1 (en) | 2012-02-13 | 2020-01-08 | Seattle Children's Hospital d/b/a Seattle Children's Research Institute | Bispecific chimeric antigen receptors and therapeutic uses thereof |
| WO2013126726A1 (en) | 2012-02-22 | 2013-08-29 | The Trustees Of The University Of Pennsylvania | Double transgenic t cells comprising a car and a tcr and their methods of use |
| CN107557334B (zh) | 2012-05-03 | 2021-06-25 | 弗雷德哈钦森癌症研究中心 | 增强亲和力的t细胞受体及其制备方法 |
| MY189533A (en) * | 2012-05-25 | 2022-02-16 | Univ California | Methods and compositions for rna-directed target dna modification and for rna-directed modulation of transcription |
| IL293944A (en) | 2012-08-20 | 2022-08-01 | Hutchinson Fred Cancer Res | Method and preparations for cellular immunotherapy |
| KR102198058B1 (ko) | 2012-10-02 | 2021-01-06 | 메모리얼 슬로안 케터링 캔서 센터 | 면역치료용 조성물 및 방법 |
| WO2014053882A1 (en) | 2012-10-04 | 2014-04-10 | Centre National De La Recherche Scientifique | Cell penetrating peptides for intracellular delivery of molecules |
| WO2014053881A1 (en) * | 2012-10-04 | 2014-04-10 | Centre National De La Recherche Scientifique | Cell penetrating peptides for intracellular delivery of molecules |
| WO2014053879A1 (en) * | 2012-10-04 | 2014-04-10 | Centre National De La Recherche Scientifique | Cell penetrating peptides for intracellular delivery of molecules |
| WO2014053880A1 (en) | 2012-10-04 | 2014-04-10 | Centre National De La Recherche Scientifique | Cell penetrating peptides for intracellular delivery of molecules |
| WO2014065596A1 (en) * | 2012-10-23 | 2014-05-01 | Toolgen Incorporated | Composition for cleaving a target dna comprising a guide rna specific for the target dna and cas protein-encoding nucleic acid or cas protein, and use thereof |
| US20160208272A1 (en) | 2013-08-22 | 2016-07-21 | E. I. Du Pont De Nemours And Company | Plant genome modification using guide rna/cas endonuclease systems and methods of use |
| US9737604B2 (en) * | 2013-09-06 | 2017-08-22 | President And Fellows Of Harvard College | Use of cationic lipids to deliver CAS9 |
| CA2933134A1 (en) * | 2013-12-13 | 2015-06-18 | Cellectis | Cas9 nuclease platform for microalgae genome engineering |
| CN107406838A (zh) * | 2014-11-06 | 2017-11-28 | 纳幕尔杜邦公司 | Rna引导的内切核酸酶向细胞中的肽介导的递送 |
| PL3237436T3 (pl) * | 2014-12-24 | 2020-03-31 | Aadigen, Llc | Peptydy i nanocząsteczki do wewnątrzkomórkowego dostarczania cząsteczek |
-
2017
- 2017-05-26 CN CN202311385196.6A patent/CN117431234A/zh active Pending
- 2017-05-26 EP EP17733918.1A patent/EP3464323B1/en active Active
- 2017-05-26 ES ES17733918T patent/ES2901215T3/es active Active
- 2017-05-26 AU AU2017268842A patent/AU2017268842B2/en active Active
- 2017-05-26 CN CN201780045854.3A patent/CN109689677B/zh active Active
- 2017-05-26 CA CA3025523A patent/CA3025523A1/en active Pending
- 2017-05-26 EP EP21170389.7A patent/EP3910059A1/en active Pending
- 2017-05-26 JP JP2018561967A patent/JP2019521659A/ja active Pending
- 2017-05-26 WO PCT/US2017/034862 patent/WO2017205846A1/en not_active Ceased
- 2017-05-26 MX MX2018014599A patent/MX388294B/es unknown
-
2018
- 2018-11-21 ZA ZA2018/07869A patent/ZA201807869B/en unknown
- 2018-11-27 MX MX2021014704A patent/MX2021014704A/es unknown
-
2021
- 2021-11-11 JP JP2021184056A patent/JP7379447B2/ja active Active
-
2022
- 2022-07-21 AU AU2022206789A patent/AU2022206789B9/en active Active
-
2023
- 2023-09-29 JP JP2023169638A patent/JP2023165986A/ja not_active Withdrawn
-
2025
- 2025-05-12 JP JP2025079827A patent/JP2025118829A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| MX2018014599A (es) | 2019-02-28 |
| CN109689677B (zh) | 2023-11-10 |
| AU2022206789B2 (en) | 2025-09-04 |
| JP2023165986A (ja) | 2023-11-17 |
| JP7379447B2 (ja) | 2023-11-14 |
| JP2022023229A (ja) | 2022-02-07 |
| CN109689677A (zh) | 2019-04-26 |
| JP2025118829A (ja) | 2025-08-13 |
| JP2019521659A (ja) | 2019-08-08 |
| AU2022206789B9 (en) | 2025-09-18 |
| AU2022206789A1 (en) | 2022-10-06 |
| MX388294B (es) | 2025-03-19 |
| AU2017268842B2 (en) | 2022-08-11 |
| EP3464323A1 (en) | 2019-04-10 |
| EP3910059A1 (en) | 2021-11-17 |
| WO2017205846A1 (en) | 2017-11-30 |
| EP3464323B1 (en) | 2021-09-22 |
| CA3025523A1 (en) | 2017-11-30 |
| AU2017268842A1 (en) | 2018-12-13 |
| MX2021014704A (es) | 2022-01-11 |
| ZA201807869B (en) | 2022-08-31 |
| CN117431234A (zh) | 2024-01-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2901215T3 (es) | Péptidos y nanopartículas para la liberación intracelular de moléculas de edición del genoma | |
| US20250257342A1 (en) | Peptides and nanoparticles for intracellular delivery of genome-editing molecules | |
| JP7148936B2 (ja) | ＣＲＩＳＰＲ関連方法および支配ｇＲＮＡのある組成物 | |
| US20230365951A1 (en) | Tracking and Manipulating Cellular RNA via Nuclear Delivery of CRISPR/CAS9 | |
| US11713336B2 (en) | Peptides and nanoparticles for intracellular delivery of molecules | |
| AU2018352221B2 (en) | Peptides and nanoparticles for intracellular delivery of mRNA | |
| EP3230460B1 (en) | Methods and compositions for selectively eliminating cells of interest | |
| US20200172913A1 (en) | Peptides and nanoparticles for intracellular delivery of virus | |
| HK40064529A (en) | Peptides and nanoparticles for intracellular delivery of genome-editing molecules | |
| HK40006957B (en) | Peptides and nanoparticles for intracellular delivery of genome-editing molecules | |
| HK1244841B (en) | Methods and compositions for selectively eliminating cells of interest |