AU8006400B2

AU8006400B2 -

Info

Publication number: AU8006400B2
Authority: AU; Australia
Prior art keywords: lipid; composition; liposomes; moiety; liposome
Prior art date: 2004-12-23
Legal status : Active

Application number

Other languages

English (en)

Publication date

2004-12-23

Links

239000002502 liposome Substances 0.000 claims description 130
150000002632 lipids Chemical class 0.000 claims description 128
229920003013 deoxyribonucleic acid Polymers 0.000 claims description 48
239000000203 mixture Substances 0.000 claims description 42
210000004027 cells Anatomy 0.000 claims description 37
150000007523 nucleic acids Chemical group 0.000 claims description 33
108020004707 nucleic acids Proteins 0.000 claims description 31
229920001477 hydrophilic polymer Polymers 0.000 claims description 18
230000027455 binding Effects 0.000 claims description 17
RAXXELZNTBOGNW-UHFFFAOYSA-N Imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 16
125000004432 carbon atoms Chemical group C* 0.000 claims description 16
150000001875 compounds Chemical class 0.000 claims description 16
102000004169 proteins and genes Human genes 0.000 claims description 15
108090000623 proteins and genes Proteins 0.000 claims description 15
239000002202 Polyethylene glycol Substances 0.000 claims description 12
239000003446 ligand Substances 0.000 claims description 12
MYMOFIZGZYHOMD-UHFFFAOYSA-N oxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 12
239000001301 oxygen Substances 0.000 claims description 12
229910052760 oxygen Inorganic materials 0.000 claims description 12
229920001223 polyethylene glycol Polymers 0.000 claims description 12
125000003342 alkenyl group Chemical group 0.000 claims description 11
125000002883 imidazolyl group Chemical group 0.000 claims description 11
125000005466 alkylenyl group Chemical group 0.000 claims description 10
KXDHJXZQYSOELW-UHFFFAOYSA-M carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 10
229920000160 (ribonucleotides)n+m Polymers 0.000 claims description 9
239000003814 drug Substances 0.000 claims description 9
150000004982 aromatic amines Chemical class 0.000 claims description 8
150000002337 glycosamines Chemical class 0.000 claims description 8
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate dianion Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 6
150000002148 esters Chemical class 0.000 claims description 6
210000004881 tumor cells Anatomy 0.000 claims description 6
230000000052 comparative effect Effects 0.000 claims description 4
230000000295 complement Effects 0.000 claims description 4
230000001225 therapeutic Effects 0.000 claims description 4
230000003511 endothelial Effects 0.000 claims description 3
101710042656 BQ2027_MB1231C Proteins 0.000 claims description 2
108010024212 E-Selectin Proteins 0.000 claims description 2
101710003421 FGF Proteins 0.000 claims description 2
102000015689 E-Selectin Human genes 0.000 claims 1
239000003795 chemical substances by application Substances 0.000 description 18
238000002360 preparation method Methods 0.000 description 16
NTYJJOPFIAHURM-UHFFFAOYSA-N histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 14
230000001264 neutralization Effects 0.000 description 14
WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 14
HVYWMOMLDIMFJA-DPAQBDIFSA-N (3β)-Cholest-5-en-3-ol 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 description 12
102000004965 antibodies Human genes 0.000 description 11
108090001123 antibodies Proteins 0.000 description 11
-1 sulfonium ion Chemical class 0.000 description 11
230000000692 anti-sense Effects 0.000 description 8
239000011248 coating agent Substances 0.000 description 8
238000000576 coating method Methods 0.000 description 8
238000000034 method Methods 0.000 description 8
239000000232 Lipid Bilayer Substances 0.000 description 7
108020004999 Messenger RNA Proteins 0.000 description 7
239000010408 film Substances 0.000 description 7
229960001340 histamine Drugs 0.000 description 7
229920002106 messenger RNA Polymers 0.000 description 7
229940107161 Cholesterol Drugs 0.000 description 6
102000007260 Deoxyribonuclease I Human genes 0.000 description 6
108010008532 Deoxyribonuclease I Proteins 0.000 description 6
102000016911 Deoxyribonucleases Human genes 0.000 description 6
108010053770 Deoxyribonucleases Proteins 0.000 description 6
201000011510 cancer Diseases 0.000 description 6
235000012000 cholesterol Nutrition 0.000 description 6
239000012528 membrane Substances 0.000 description 6
OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
150000003904 phospholipids Chemical class 0.000 description 6
229920000642 polymer Polymers 0.000 description 6
239000007787 solid Substances 0.000 description 6
239000000243 solution Substances 0.000 description 6
UHUSDOQQWJGJQS-UHFFFAOYSA-N Glycerol 1,2-dioctadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(CO)OC(=O)CCCCCCCCCCCCCCCCC UHUSDOQQWJGJQS-UHFFFAOYSA-N 0.000 description 5
238000006243 chemical reaction Methods 0.000 description 5
PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerol Substances OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
239000000463 material Substances 0.000 description 5
238000001890 transfection Methods 0.000 description 5
GXYPITRJSPDNLU-UHFFFAOYSA-M (4-nitrophenyl)chloranuidylformate Chemical compound [O-]C(=O)[Cl-]C1=CC=C([N+]([O-])=O)C=C1 GXYPITRJSPDNLU-UHFFFAOYSA-M 0.000 description 4
LVNGJLRDBYCPGB-LDLOPFEMSA-N (R)-1,2-distearoylphosphatidylethanolamine zwitterion Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[NH3+])OC(=O)CCCCCCCCCCCCCCCCC LVNGJLRDBYCPGB-LDLOPFEMSA-N 0.000 description 4
235000010469 Glycine max Nutrition 0.000 description 4
206010028980 Neoplasm Diseases 0.000 description 4
229920000272 Oligonucleotide Polymers 0.000 description 4
229940067631 Phospholipids Drugs 0.000 description 4
150000001412 amines Chemical class 0.000 description 4
RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
238000000799 fluorescence microscopy Methods 0.000 description 4
230000002209 hydrophobic Effects 0.000 description 4
102000005962 receptors Human genes 0.000 description 4
108020003175 receptors Proteins 0.000 description 4
XSQUKJJJFZCRTK-UHFFFAOYSA-N urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
LOVPHSMOAVXQIH-UHFFFAOYSA-M (4-nitrophenyl) carbonate Chemical compound [O-]C(=O)OC1=CC=C([N+]([O-])=O)C=C1 LOVPHSMOAVXQIH-UHFFFAOYSA-M 0.000 description 3
GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 3
102100000129 CHURC1 Human genes 0.000 description 3
101710014631 CHURC1 Proteins 0.000 description 3
210000004072 Lung Anatomy 0.000 description 3
239000011543 agarose gel Substances 0.000 description 3
125000000217 alkyl group Chemical group 0.000 description 3
238000004166 bioassay Methods 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
229910052799 carbon Inorganic materials 0.000 description 3
125000002091 cationic group Chemical group 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
238000009472 formulation Methods 0.000 description 3
238000001415 gene therapy Methods 0.000 description 3
230000000887 hydrating Effects 0.000 description 3
150000002430 hydrocarbons Chemical group 0.000 description 3
238000000338 in vitro Methods 0.000 description 3
238000004519 manufacturing process Methods 0.000 description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
238000000386 microscopy Methods 0.000 description 3
229920000023 polynucleotide Polymers 0.000 description 3
239000002157 polynucleotide Substances 0.000 description 3
239000002904 solvent Substances 0.000 description 3
238000003756 stirring Methods 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
230000002194 synthesizing Effects 0.000 description 3
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
FKLJPTJMIBLJAV-UHFFFAOYSA-N 5-(7-(4-(4,5-DIHYDRO-2-OXAZOLYL)PHENOXY)HEPTYL)-3-METHYL ISOXAZOLE Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 2
208000003174 Brain Neoplasms Diseases 0.000 description 2
206010006187 Breast cancer Diseases 0.000 description 2
229920001405 Coding region Polymers 0.000 description 2
WQZGKKKJIJFFOK-GASJEMHNSA-N D-Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
102100010813 EGF Human genes 0.000 description 2
101700033006 EGF Proteins 0.000 description 2
210000001163 Endosomes Anatomy 0.000 description 2
229940116977 Epidermal Growth Factor Drugs 0.000 description 2
ZMMJGEGLRURXTF-UHFFFAOYSA-N Ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 2
230000035693 Fab Effects 0.000 description 2
LKQLRGMMMAHREN-YJFXYUILSA-N N-stearoylsphingosine-1-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)N[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)[C@H](O)\C=C\CCCCCCCCCCCCC LKQLRGMMMAHREN-YJFXYUILSA-N 0.000 description 2
206010033128 Ovarian cancer Diseases 0.000 description 2
ATHGHQPFGPMSJY-UHFFFAOYSA-N Spermidine Chemical compound NCCCCNCCCN ATHGHQPFGPMSJY-UHFFFAOYSA-N 0.000 description 2
PFNFFQXMRSDOHW-UHFFFAOYSA-N Spermine Chemical compound NCCCNCCCCNCCCN PFNFFQXMRSDOHW-UHFFFAOYSA-N 0.000 description 2
WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 2
239000002253 acid Substances 0.000 description 2
230000002378 acidificating Effects 0.000 description 2
UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
230000017531 blood circulation Effects 0.000 description 2
239000004202 carbamide Substances 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
230000015556 catabolic process Effects 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
230000004059 degradation Effects 0.000 description 2
238000006731 degradation reaction Methods 0.000 description 2
238000001212 derivatisation Methods 0.000 description 2
239000010432 diamond Substances 0.000 description 2
UMGXUWVIJIQANV-UHFFFAOYSA-M didecyl(dimethyl)azanium;bromide Chemical compound [Br-].CCCCCCCCCC[N+](C)(C)CCCCCCCCCC UMGXUWVIJIQANV-UHFFFAOYSA-M 0.000 description 2
OGQYPPBGSLZBEG-UHFFFAOYSA-N dimethyl(dioctadecyl)azanium Chemical compound CCCCCCCCCCCCCCCCCC[N+](C)(C)CCCCCCCCCCCCCCCCCC OGQYPPBGSLZBEG-UHFFFAOYSA-N 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
MWRBNPKJOOWZPW-CLFAGFIQSA-N dioleoyl phosphatidylethanolamine Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(COP(O)(=O)OCCN)OC(=O)CCCCCCC\C=C/CCCCCCCC MWRBNPKJOOWZPW-CLFAGFIQSA-N 0.000 description 2
150000002009 diols Chemical class 0.000 description 2
229940079593 drugs Drugs 0.000 description 2
238000002296 dynamic light scattering Methods 0.000 description 2
238000005516 engineering process Methods 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
238000001502 gel electrophoresis Methods 0.000 description 2
230000002068 genetic Effects 0.000 description 2
239000008103 glucose Substances 0.000 description 2
230000036571 hydration Effects 0.000 description 2
238000006703 hydration reaction Methods 0.000 description 2
239000001257 hydrogen Substances 0.000 description 2
229910052739 hydrogen Inorganic materials 0.000 description 2
125000004435 hydrogen atoms Chemical class [H]* 0.000 description 2
230000003053 immunization Effects 0.000 description 2
102000006495 integrins Human genes 0.000 description 2
108010044426 integrins Proteins 0.000 description 2
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 2
239000010410 layer Substances 0.000 description 2
239000007788 liquid Substances 0.000 description 2
238000005259 measurement Methods 0.000 description 2
239000000693 micelle Substances 0.000 description 2
238000001000 micrograph Methods 0.000 description 2
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
239000002773 nucleotide Substances 0.000 description 2
125000003729 nucleotide group Chemical group 0.000 description 2
239000002245 particle Substances 0.000 description 2
239000002831 pharmacologic agent Substances 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
239000011148 porous material Substances 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
239000011541 reaction mixture Substances 0.000 description 2
229920002033 ribozyme Polymers 0.000 description 2
238000004513 sizing Methods 0.000 description 2
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 2
150000003432 sterols Chemical class 0.000 description 2
235000003702 sterols Nutrition 0.000 description 2
239000000725 suspension Substances 0.000 description 2
238000002560 therapeutic procedure Methods 0.000 description 2
ZMANZCXQSJIPKH-UHFFFAOYSA-N triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 2
238000002255 vaccination Methods 0.000 description 2
230000003612 virological Effects 0.000 description 2
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
WPWJFABXGZAMQI-SFHVURJKSA-N (2S)-2-(hexadecanoylamino)-4-sulfanylbutanoic acid Chemical compound CCCCCCCCCCCCCCCC(=O)N[C@H](C(O)=O)CCS WPWJFABXGZAMQI-SFHVURJKSA-N 0.000 description 1
ZAKBPRIDLSBYQQ-VHSXEESVSA-N 1,2-diacyl-sn-glycero-3-phospho-(1'-sn-glycerol) Chemical compound CC(=O)OC[C@@H](OC(C)=O)COP(O)(=O)OC[C@@H](O)CO ZAKBPRIDLSBYQQ-VHSXEESVSA-N 0.000 description 1
OIUZBDNWEHNDHO-UHFFFAOYSA-N 2-(2,2-dimethyl-1,3-dioxolan-4-yl)acetic acid Chemical compound CC1(C)OCC(CC(O)=O)O1 OIUZBDNWEHNDHO-UHFFFAOYSA-N 0.000 description 1
KQIGMPWTAHJUMN-UHFFFAOYSA-N 3-aminopropane-1,2-diol Chemical compound NCC(O)CO KQIGMPWTAHJUMN-UHFFFAOYSA-N 0.000 description 1
CWSZBVAUYPTXTG-UHFFFAOYSA-N 5-[6-[[3,4-dihydroxy-6-(hydroxymethyl)-5-methoxyoxan-2-yl]oxymethyl]-3,4-dihydroxy-5-[4-hydroxy-3-(2-hydroxyethoxy)-6-(hydroxymethyl)-5-methoxyoxan-2-yl]oxyoxan-2-yl]oxy-6-(hydroxymethyl)-2-methyloxane-3,4-diol Chemical compound O1C(CO)C(OC)C(O)C(O)C1OCC1C(OC2C(C(O)C(OC)C(CO)O2)OCCO)C(O)C(O)C(OC2C(OC(C)C(O)C2O)CO)O1 CWSZBVAUYPTXTG-UHFFFAOYSA-N 0.000 description 1
206010000565 Acquired immunodeficiency syndrome Diseases 0.000 description 1
102000036638 BRCA1 Human genes 0.000 description 1
108010042977 BRCA1 Protein Proteins 0.000 description 1
102000002280 BRCA2 Protein Human genes 0.000 description 1
108010000750 BRCA2 Protein Proteins 0.000 description 1
WNGKSRISYMBBEJ-UHFFFAOYSA-N CC([CH2-])=O.OCC(O)C(O)=O.CC1(C)OCC(C(O)=O)O1 Chemical class CC([CH2-])=O.OCC(O)C(O)=O.CC1(C)OCC(C(O)=O)O1 WNGKSRISYMBBEJ-UHFFFAOYSA-N 0.000 description 1
102100005826 CD19 Human genes 0.000 description 1
101700087100 CD19 Proteins 0.000 description 1
108010041397 CD4 Antigens Proteins 0.000 description 1
102000033243 CDKN2A Human genes 0.000 description 1
210000001736 Capillaries Anatomy 0.000 description 1
108090000994 Catalytic RNA Proteins 0.000 description 1
102000000844 Cell Surface Receptors Human genes 0.000 description 1
108010001857 Cell Surface Receptors Proteins 0.000 description 1
206010010099 Combined immunodeficiency Diseases 0.000 description 1
229920002676 Complementary DNA Polymers 0.000 description 1
108010009392 Cyclin-Dependent Kinase Inhibitor p16 Proteins 0.000 description 1
210000000805 Cytoplasm Anatomy 0.000 description 1
102000006815 Folate receptors Human genes 0.000 description 1
108020005243 Folate receptors Proteins 0.000 description 1
240000007842 Glycine max Species 0.000 description 1
102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
102000009465 Growth Factor Receptors Human genes 0.000 description 1
108010009202 Growth Factor Receptors Proteins 0.000 description 1
108010091938 HLA-B7 Antigen Proteins 0.000 description 1
229940031574 HYDROXYMETHYL CELLULOSE Drugs 0.000 description 1
229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
102000004218 Insulin-like growth factor I Human genes 0.000 description 1
108090000723 Insulin-like growth factor I Proteins 0.000 description 1
108010002350 Interleukin-2 Proteins 0.000 description 1
108090000978 Interleukin-4 Proteins 0.000 description 1
239000005089 Luciferase Substances 0.000 description 1
108060001084 Luciferase family Proteins 0.000 description 1
206010058467 Lung neoplasm malignant Diseases 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
206010025650 Malignant melanoma Diseases 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
206010027406 Mesothelioma Diseases 0.000 description 1
101700080605 NUC1 Proteins 0.000 description 1
206010029260 Neuroblastoma Diseases 0.000 description 1
229920002332 Noncoding DNA Polymers 0.000 description 1
108010035766 P-Selectin Proteins 0.000 description 1
UNJJBGNPUUVVFQ-ZJUUUORDSA-N Phosphatidylserine Chemical compound CCCC(=O)O[C@H](COC(=O)CC)COP(O)(=O)OC[C@H](N)C(O)=O UNJJBGNPUUVVFQ-ZJUUUORDSA-N 0.000 description 1
229950008679 Protamine sulfate Drugs 0.000 description 1
208000006265 Renal Cell Carcinoma Diseases 0.000 description 1
229920001914 Ribonucleotide Polymers 0.000 description 1
102100003520 SELE Human genes 0.000 description 1
102100017680 SMAD4 Human genes 0.000 description 1
101700062085 SMAD4 Proteins 0.000 description 1
208000009642 Severe combined immunodeficiency due to adenosine deaminase deficiency Diseases 0.000 description 1
108020004682 Single-Stranded DNA Proteins 0.000 description 1
WWUZIQQURGPMPG-KRWOKUGFSA-N Sphingosine Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)CO WWUZIQQURGPMPG-KRWOKUGFSA-N 0.000 description 1
102100019730 TP53 Human genes 0.000 description 1
101710026335 TP53 Proteins 0.000 description 1
102000006601 Thymidine Kinase Human genes 0.000 description 1
108020004440 Thymidine Kinase Proteins 0.000 description 1
108091007928 VEGF receptors Proteins 0.000 description 1
102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 1
102100008060 WT1 Human genes 0.000 description 1
101700062995 WT1 Proteins 0.000 description 1
230000003213 activating Effects 0.000 description 1
239000011149 active material Substances 0.000 description 1
125000002252 acyl group Chemical group 0.000 description 1
201000009628 adenosine deaminase deficiency Diseases 0.000 description 1
150000001299 aldehydes Chemical class 0.000 description 1
230000004075 alteration Effects 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-O ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
PAYRUJLWNCNPSJ-UHFFFAOYSA-N aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 1
239000000427 antigen Substances 0.000 description 1
102000038129 antigens Human genes 0.000 description 1
108091007172 antigens Proteins 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
239000007900 aqueous suspension Substances 0.000 description 1
239000003012 bilayer membrane Substances 0.000 description 1
230000005540 biological transmission Effects 0.000 description 1
229920001400 block copolymer Polymers 0.000 description 1
150000001784 cerebrosides Chemical class 0.000 description 1
125000003636 chemical group Chemical group 0.000 description 1
102000009410 chemokine receptors Human genes 0.000 description 1
108050000299 chemokine receptors Proteins 0.000 description 1
238000010367 cloning Methods 0.000 description 1
201000011231 colorectal cancer Diseases 0.000 description 1
201000010989 colorectal carcinoma Diseases 0.000 description 1
239000002299 complementary DNA Substances 0.000 description 1
238000010192 crystallographic characterization Methods 0.000 description 1
201000003883 cystic fibrosis Diseases 0.000 description 1
230000003247 decreasing Effects 0.000 description 1
150000001982 diacylglycerols Chemical class 0.000 description 1
239000000032 diagnostic agent Substances 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
230000029087 digestion Effects 0.000 description 1
230000000694 effects Effects 0.000 description 1
235000013601 eggs Nutrition 0.000 description 1
238000004520 electroporation Methods 0.000 description 1
238000005538 encapsulation Methods 0.000 description 1
230000012202 endocytosis Effects 0.000 description 1
239000003623 enhancer Substances 0.000 description 1
230000002708 enhancing Effects 0.000 description 1
BRLQWZUYTZBJKN-UHFFFAOYSA-N epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 1
150000002118 epoxides Chemical class 0.000 description 1
LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
238000001125 extrusion Methods 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
150000004665 fatty acids Chemical class 0.000 description 1
210000002950 fibroblast Anatomy 0.000 description 1
150000002270 gangliosides Chemical class 0.000 description 1
239000000499 gel Substances 0.000 description 1
238000000265 homogenisation Methods 0.000 description 1
229920001519 homopolymer Polymers 0.000 description 1
239000008350 hydrogenated phosphatidyl choline Substances 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
230000003301 hydrolyzing Effects 0.000 description 1
235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
200000000018 inflammatory disease Diseases 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
230000002452 interceptive Effects 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
238000005304 joining Methods 0.000 description 1
125000000468 ketone group Chemical group 0.000 description 1
GZQKNULLWNGMCW-PWQABINMSA-J lipid A(4-) Chemical compound O1[C@H](CO)[C@@H](OP([O-])([O-])=O)[C@H](OC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCCCC)[C@@H](NC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCC)[C@@H]1OC[C@@H]1[C@@H](O)[C@H](OC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](NC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](OP([O-])([O-])=O)O1 GZQKNULLWNGMCW-PWQABINMSA-J 0.000 description 1
150000002634 lipophilic molecules Chemical class 0.000 description 1
238000011068 load Methods 0.000 description 1
201000005202 lung cancer Diseases 0.000 description 1
230000002132 lysosomal Effects 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 description 1
230000003211 malignant Effects 0.000 description 1
230000001404 mediated Effects 0.000 description 1
201000001441 melanoma Diseases 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
125000006357 methylene carbonyl group Chemical group [H]C([H])([*:1])C([*:2])=O 0.000 description 1
YACKEPLHDIMKIO-UHFFFAOYSA-L methylphosphonate(2-) Chemical compound CP([O-])([O-])=O YACKEPLHDIMKIO-UHFFFAOYSA-L 0.000 description 1
CSNNHWWHGAXBCP-UHFFFAOYSA-L mgso4 Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
244000005700 microbiome Species 0.000 description 1
238000000520 microinjection Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000006011 modification reaction Methods 0.000 description 1
230000035772 mutation Effects 0.000 description 1
125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
101700006494 nucA Proteins 0.000 description 1
125000002811 oleoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])/C([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])[H] 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
230000037361 pathway Effects 0.000 description 1
150000008103 phosphatidic acids Chemical class 0.000 description 1
150000008105 phosphatidylcholines Chemical class 0.000 description 1
150000008104 phosphatidylethanolamines Chemical class 0.000 description 1
150000003905 phosphatidylinositols Chemical class 0.000 description 1
150000004713 phosphodiesters Chemical class 0.000 description 1
239000000902 placebo Substances 0.000 description 1
229940068196 placebo Drugs 0.000 description 1
229920000068 poly(2-ethyl-2-oxazoline) Polymers 0.000 description 1
229920002432 poly(vinyl methyl ether) polymer Polymers 0.000 description 1
239000004417 polycarbonate Substances 0.000 description 1
229920000515 polycarbonate Polymers 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
OZAIFHULBGXAKX-UHFFFAOYSA-N precursor Substances N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
229920005604 random copolymer Polymers 0.000 description 1
230000022983 regulation of cell cycle Effects 0.000 description 1
230000004044 response Effects 0.000 description 1
239000002336 ribonucleotide Substances 0.000 description 1
125000002652 ribonucleotide group Chemical group 0.000 description 1
238000002390 rotary evaporation Methods 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
238000000527 sonication Methods 0.000 description 1
229940063673 spermidine Drugs 0.000 description 1
229940063675 spermine Drugs 0.000 description 1
125000002345 steroid group Chemical group 0.000 description 1
239000000126 substance Substances 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
239000010409 thin film Substances 0.000 description 1
RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1