JP2020536125A5 - - Google Patents

Info

Publication number

JP2020536125A5

JP2020536125A5 JP2020540244A JP2020540244A JP2020536125A5 JP 2020536125 A5 JP2020536125 A5 JP 2020536125A5 JP 2020540244 A JP2020540244 A JP 2020540244A JP 2020540244 A JP2020540244 A JP 2020540244A JP 2020536125 A5 JP2020536125 A5 JP 2020536125A5

Authority

JP

Japan

Prior art keywords

lipid

composition according

lnp composition

mol

lnp

Prior art date

2018-09-28

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.)

Granted

Links

• Espacenet
• Global Dossier
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• 239000000203 mixture Substances 0.000 claims description 126
• 150000002632 lipids Chemical class 0.000 claims description 86
• 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 39
• 108020004999 messenger RNA Proteins 0.000 claims description 34
• 108020005004 Guide RNA Proteins 0.000 claims description 32
• -1 amine lipids Chemical class 0.000 claims description 30
• DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 claims description 24
• 238000000034 method Methods 0.000 claims description 17
• 125000003729 nucleotide group Chemical group 0.000 claims description 16
• 101710163270 Nuclease Proteins 0.000 claims description 14
• 150000003626 triacylglycerols Chemical class 0.000 claims description 13
• DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 claims description 12
• DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 claims description 12
• 229940045145 uridine Drugs 0.000 claims description 12
• 239000002773 nucleotide Substances 0.000 claims description 11
• 108700026244 Open Reading Frames Proteins 0.000 claims description 9
• 230000007935 neutral effect Effects 0.000 claims description 8
• 230000004568 DNA-binding Effects 0.000 claims description 7
• 238000012986 modification Methods 0.000 claims description 6
• 230000004048 modification Effects 0.000 claims description 6
• 238000010362 genome editing Methods 0.000 claims description 5
• 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 4
• LKPJRFVEJFVTFQ-UHFFFAOYSA-N hentriacontane-15,16,17-triol Chemical compound CCCCCCCCCCCCCCC(O)C(O)C(O)CCCCCCCCCCCCCC LKPJRFVEJFVTFQ-UHFFFAOYSA-N 0.000 claims description 4
• GZQKNULLWNGMCW-PWQABINMSA-N lipid A (E. coli) 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-N 0.000 claims description 4
• 150000003904 phospholipids Chemical class 0.000 claims description 4
• RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims description 4
• 108020004707 nucleic acids Proteins 0.000 claims description 3
• 150000007523 nucleic acids Chemical class 0.000 claims description 3
• 102000039446 nucleic acids Human genes 0.000 claims description 3
• KILNVBDSWZSGLL-KXQOOQHDSA-N 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCC KILNVBDSWZSGLL-KXQOOQHDSA-N 0.000 claims description 2
• NRJAVPSFFCBXDT-HUESYALOSA-N 1,2-distearoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCCCC NRJAVPSFFCBXDT-HUESYALOSA-N 0.000 claims description 2
• 108091033409 CRISPR Proteins 0.000 claims description 2
• 235000012000 cholesterol Nutrition 0.000 claims description 2
• 238000004519 manufacturing process Methods 0.000 claims description 2
• 239000002105 nanoparticle Substances 0.000 claims description 2
• 125000000217 alkyl group Chemical group 0.000 claims 2
• 229930188104 Alkylresorcinol Natural products 0.000 claims 1
• 125000006538 C11 alkyl 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])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
• 125000006539 C12 alkyl 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])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
• 229930182558 Sterol Natural products 0.000 claims 1
• 230000027455 binding Effects 0.000 claims 1
• 125000002704 decyl 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])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
• 239000003814 drug Substances 0.000 claims 1
• 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
• 125000001400 nonyl 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])[H] 0.000 claims 1
• 150000003431 steroids Chemical class 0.000 claims 1
• 150000003432 sterols Chemical class 0.000 claims 1
• 235000003702 sterols Nutrition 0.000 claims 1
• DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 8
• 150000001241 acetals Chemical class 0.000 description 6
• UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 2
• 108091027544 Subgenomic mRNA Proteins 0.000 description 1