IL309001A - Antisense compounds and methods for targeting cug repeats - Google Patents
Antisense compounds and methods for targeting cug repeatsInfo
- Publication number
- IL309001A IL309001A IL309001A IL30900123A IL309001A IL 309001 A IL309001 A IL 309001A IL 309001 A IL309001 A IL 309001A IL 30900123 A IL30900123 A IL 30900123A IL 309001 A IL309001 A IL 309001A
- Authority
- IL
- Israel
- Prior art keywords
- compound
- cag cag
- peptide
- side chain
- amino acid
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims 50
- 230000000692 anti-sense effect Effects 0.000 title claims 12
- 230000008685 targeting Effects 0.000 title 1
- 150000001413 amino acids Chemical class 0.000 claims 14
- 108090000765 processed proteins & peptides Proteins 0.000 claims 11
- 125000005647 linker group Chemical group 0.000 claims 8
- 108010069514 Cyclic Peptides Proteins 0.000 claims 7
- 102000001189 Cyclic Peptides Human genes 0.000 claims 7
- 125000003118 aryl group Chemical group 0.000 claims 5
- 230000002209 hydrophobic effect Effects 0.000 claims 3
- 108090000623 proteins and genes Proteins 0.000 claims 3
- 210000001519 tissue Anatomy 0.000 claims 3
- IYKLZBIWFXPUCS-VIFPVBQESA-N (2s)-2-(naphthalen-1-ylamino)propanoic acid Chemical compound C1=CC=C2C(N[C@@H](C)C(O)=O)=CC=CC2=C1 IYKLZBIWFXPUCS-VIFPVBQESA-N 0.000 claims 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims 2
- 239000002202 Polyethylene glycol Substances 0.000 claims 2
- 125000000539 amino acid group Chemical group 0.000 claims 2
- 230000000295 complement effect Effects 0.000 claims 2
- 125000001072 heteroaryl group Chemical group 0.000 claims 2
- 108020004999 messenger RNA Proteins 0.000 claims 2
- 210000003205 muscle Anatomy 0.000 claims 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims 2
- 229920001223 polyethylene glycol Polymers 0.000 claims 2
- 102000004169 proteins and genes Human genes 0.000 claims 2
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims 1
- 239000004475 Arginine Substances 0.000 claims 1
- 239000004215 Carbon black (E152) Substances 0.000 claims 1
- 108010051109 Cell-Penetrating Peptides Proteins 0.000 claims 1
- 102000020313 Cell-Penetrating Peptides Human genes 0.000 claims 1
- QUOGESRFPZDMMT-UHFFFAOYSA-N L-Homoarginine Natural products OC(=O)C(N)CCCCNC(N)=N QUOGESRFPZDMMT-UHFFFAOYSA-N 0.000 claims 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims 1
- QUOGESRFPZDMMT-YFKPBYRVSA-N L-homoarginine Chemical compound OC(=O)[C@@H](N)CCCCNC(N)=N QUOGESRFPZDMMT-YFKPBYRVSA-N 0.000 claims 1
- 206010068871 Myotonic dystrophy Diseases 0.000 claims 1
- YDGMGEXADBMOMJ-LURJTMIESA-N N(g)-dimethylarginine Chemical compound CN(C)C(\N)=N\CCC[C@H](N)C(O)=O YDGMGEXADBMOMJ-LURJTMIESA-N 0.000 claims 1
- NTWVQPHTOUKMDI-YFKPBYRVSA-N N-Methyl-arginine Chemical compound CN[C@H](C(O)=O)CCCN=C(N)N NTWVQPHTOUKMDI-YFKPBYRVSA-N 0.000 claims 1
- 108091034117 Oligonucleotide Proteins 0.000 claims 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims 1
- -1 aromatic amino acids Chemical class 0.000 claims 1
- YDGMGEXADBMOMJ-UHFFFAOYSA-N asymmetrical dimethylarginine Natural products CN(C)C(N)=NCCCC(N)C(O)=O YDGMGEXADBMOMJ-UHFFFAOYSA-N 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 125000004122 cyclic group Chemical group 0.000 claims 1
- 229930195733 hydrocarbon Natural products 0.000 claims 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
Classifications
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- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/712—Nucleic acids or oligonucleotides having modified sugars, i.e. other than ribose or 2'-deoxyribose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
- A61K47/645—Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT
- A61K47/6455—Polycationic oligopeptides, polypeptides or polyamino acids, e.g. for complexing nucleic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/64—Cyclic peptides containing only normal peptide links
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/07—Animals genetically altered by homologous recombination
- A01K2217/072—Animals genetically altered by homologous recombination maintaining or altering function, i.e. knock in
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2227/00—Animals characterised by species
- A01K2227/10—Mammal
- A01K2227/105—Murine
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
- A01K2267/0306—Animal model for genetic diseases
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- 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
- C12N2310/11—Antisense
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- 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
- C12N2310/30—Chemical structure
- C12N2310/32—Chemical structure of the sugar
- C12N2310/323—Chemical structure of the sugar modified ring structure
- C12N2310/3233—Morpholino-type ring
-
- 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
- C12N2310/30—Chemical structure
- C12N2310/35—Nature of the modification
- C12N2310/351—Conjugate
- C12N2310/3513—Protein; Peptide
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Biomedical Technology (AREA)
- Biophysics (AREA)
- Epidemiology (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- Neurology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Microbiology (AREA)
- Plant Pathology (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physics & Mathematics (AREA)
- Neurosurgery (AREA)
- Immunology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Claims (39)
1. A compound comprising: (a) an antisense compound that is complementary to at least a portion of an expanded CUG repeat in a target mRNA sequence; (b) a cyclic peptide of the formula: or a protonated form thereof, wherein: R1, R2, and R3 are each independently H or an aromatic or heteroaromatic side chain of an amino acid; at least one of R1, R2, and R3 is an aromatic or heteroaromatic side chain of an amino acid; R4, R5, R6, R7 are independently H or an amino acid side chain; AASC is an amino acid side chain; and q is 1, 2, 3 or 4, wherein at least two amino acids of the cyclic peptide are charged amino acids, at least two amino acids of the cyclic peptide are aromatic hydrophobic amino acids, and at least two amino acids of the cyclic peptide are uncharged, non-aromatic amino acids.
2. The compound of claim 1, wherein at least two of R1, R2, and R3 are side chains of aromatic hydrophobic amino acids.
3. The compound of claim 1, wherein at least two of R1, R2, and R3 are independently phenylalanine or naphthylalanine. 253
4. The compound of claim 1 or claim 2, wherein at least two of R5, R6, and R7 are side chains of charged amino acids.
5. The compound of claim 1 or 2, wherein at least two of R5, R6, and R7 are independently arginine, homoarginine, N-methylarginine, and N,N-dimethylarginine.
6. The compound of any one of claims 1 to 5, wherein q is 1.
7. The compound of any one of claims 1 to 6, wherein R4 is H.
8. A compound comprising: (a) an antisense compound that is complementary to at least a portion of an expanded CUG repeat in a target mRNA sequence; (b) a cyclic peptide of the formula: , , or a protonated form thereof, wherein: R1, R2, and R3 are each independently H or an amino acid residue having a side chain comprising an aromatic group; at least two of R1, R2, and R3 are the side chain of phenylalanine; R4 is H or an amino acid side chain; AASC is an amino acid side chain; and each m is independently an integer of 0, 1, 2, or 3. 254
9. The compound of claim 8, wherein one of R1, R2, and R3 is naphthylalanine.
10. The compound of claim 8, wherein one of R1, R2, and R3 is H.
11. The compound of any one of claims 8 to 10, wherein R4 is H.
12. The compound of any one of claims 1 to 11, wherein the cyclic cell penetrating peptide is selected from , , 255 , , or a protonated form thereof.
13. The compound of any one of claims 1 to 12, wherein the compound further comprises an exocyclic peptide.
14. The compound of claim 13, wherein the exocyclic peptide comprises from 2 to 10 amino acids. 256
15. The compound of claim 13 or 14, wherein the exocyclic peptide comprises 2, 3, or 4 lysine residues.
16. The compound of any one of claims 13 to 15, wherein the exocyclic peptide comprises at least 2 amino acid residues with a hydrophobic side chain.
17. The compound of any one of claims 13 to 15, wherein the exocyclic peptide comprises PGKKRKV.
18. The compound of any one of claims 13 to 15, wherein the exocyclic peptide comprises PKKKRKV.
19. The compound of any one of claims 13 to 15, wherein the exocyclic peptide comprises PKKKGKV.
20. The compound of any one of claims 13 to 15, wherein the exocyclic peptide comprises PKKKRKG.
21. The compound of any one of claims 13 to 20, further comprising a linker, wherein the linker conjugates the antisense compound and the exocyclic peptide to the cyclic peptide.
22. The compound of claim 21, wherein the linker has the following structure: , wherein A1, B1, and C1, each independently comprise a hydrocarbon linker, a polyethylene glycol (PEG) linker, or one or more amino acid residue.
23. The compound of claim 21, wherein the linker has the following formula: 257 wherein: x’ is an integer from 1-23; y is an integer from 1-5; z’ is an integer from 1-23; * is the point of attachment to the AASC of the cyclic peptide; and M is a bonding group.
24. The compound of claim 23, wherein z’ is 11.
25. The compound of claim 23 or 24, wherein x’ is 1.
26. The compound of any one of claims 23 to 25, wherein the exocyclic peptide is conjugated to the linker at the amino end of the linker and the antisense compound is conjugated to M.
27. The compound of any one of claims 23 to 26, wherein M is -C(O)-.
28. The compound of claim 23, wherein the compound is selected from 258 259 or a protonated form or salt thereof, wherein EP is the exocyclic peptide, and 260 oligonucleotide is the antisense compound.
29. The compound of any one of claims 1 to 28, wherein the antisense compound comprises AG(CAG)n, G(CAG)n, (CAG)nAG, or (CAG)nA, wherein n is an integer from 1 to 50.
30. The compound of any one of claims 1 to 28, wherein the antisense compound comprises 5 to 10 CAG repeats.
31. The compound of any one of claims 1 to 28, wherein the antisense compound comprises 5’-CAG CAG CAG CAG CAG CAG CAG CAG-3’.
32. The compound of any one of claims 1 to 28, wherein the antisense compound comprises 5’-CAG CAG CAG CAG CAG CAG CAG CAG CAG-3’.
33. The compound of any one of claims 1 to 28, wherein the antisense compound comprises 5’-CAG CAG CAG CAG CAG CAG CAG-3’.
34. The compound of any one of claims 29 or claim 33, wherein the antisense compound further comprises any one of GGGCCTTTTATTCGCGAGGGTCGGG; GAGGGCCTTTTATTCGCGAGGGTCG; TGGAGGGCCTTTTATTCGCGAGGGT; GATGGAGGGCCTTTTATTCGCGAGG; CAGATGGAGGGCCTTTTATTCGCGA; GGCAGATGGAGGGCCTTTTATTCGC; TGGGCAGATGGAGGGCCTTTTATTC; TTTGGGCAGATGGAGGGCCTTTTAT; GCTTTGGGCAGATGGAGGGCCTTTT; GAGCTTTGGGCAGATGGAGGGCCTT; CAGAGCTTTGGGCAGATGGAGGGCC; 261 TCCAGAGCTTTGGGCAGATGGAGGG; AGTCCAGAGCTTTGGGCAGATGGAG; GGAGTCCAGAGCTTTGGGCAGATGG; GTGGAGTCCAGAGCTTTGGGCAGAT; CTGTGGAGTCCAGAGCTTTGGGCAG; CACTGTGGAGTCCAGAGCTTTGGGC; GACACTGTGGAGTCCAGAGCTTTGG; CGGACACTGTGGAGTCCAGAGCTTT; CGCGGACACTGTGGAGTCCAGAGCT; ACCGCGGACACTGTGGAGTCCAGAG; AAACCGCGGACACTGTGGAGTCCAG; GCAAACCGCGGACACTGTGGAGTCC; ACGCAAACCGCGGACACTGTGGAGT; or CAACGCAAACCGCGGACACTGTGGA.
35. A pharmaceutical composition comprising the compound of any one of claims 1 to 34.
36. A method of treating myotonic dystrophy (DM) in a subject in need thereof, comprising administering the compound of any one of claims 1 to 34 or the composition of claim 35 to the subject.
37. The method of claim 36, wherein the administering results in an increase in the expression of a wild-type protein in muscle tissue, wherein the wild-type protein is expressed from a gene that does not have an expanded CUG repeat.
38. The method of 37, wherein the muscle tissue is diaphragm tissue, quadricep tissues, heat tissue, or any combination thereof.
39. The method of any one of claims 36 to 38, wherein the administration prevents or reduces foci formation.
Applications Claiming Priority (16)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US202163213900P | 2021-06-23 | 2021-06-23 | |
| US202163239847P | 2021-09-01 | 2021-09-01 | |
| US202163239671P | 2021-09-01 | 2021-09-01 | |
| US202163290892P | 2021-12-17 | 2021-12-17 | |
| US202163290960P | 2021-12-17 | 2021-12-17 | |
| US202263298565P | 2022-01-11 | 2022-01-11 | |
| US202263305071P | 2022-01-31 | 2022-01-31 | |
| US202263268577P | 2022-02-25 | 2022-02-25 | |
| US202263314369P | 2022-02-26 | 2022-02-26 | |
| US202263316634P | 2022-03-04 | 2022-03-04 | |
| US202263317856P | 2022-03-08 | 2022-03-08 | |
| US202263326201P | 2022-03-31 | 2022-03-31 | |
| US202263362295P | 2022-03-31 | 2022-03-31 | |
| US202263327179P | 2022-04-04 | 2022-04-04 | |
| US202263339250P | 2022-05-06 | 2022-05-06 | |
| PCT/US2022/034517 WO2022271818A1 (en) | 2021-06-23 | 2022-06-22 | Antisense compounds and methods for targeting cug repeats |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| IL309001A true IL309001A (en) | 2024-02-01 |
Family
ID=82608300
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL309001A IL309001A (en) | 2021-06-23 | 2022-06-22 | Antisense compounds and methods for targeting cug repeats |
Country Status (12)
| Country | Link |
|---|---|
| EP (1) | EP4359006A1 (en) |
| JP (1) | JP2024524291A (en) |
| KR (1) | KR20240038967A (en) |
| AU (1) | AU2022298774A1 (en) |
| CA (1) | CA3222824A1 (en) |
| CL (1) | CL2023003840A1 (en) |
| CO (1) | CO2023018002A2 (en) |
| DO (1) | DOP2023000279A (en) |
| EC (1) | ECSP23096162A (en) |
| IL (1) | IL309001A (en) |
| MX (1) | MX2023015509A (en) |
| WO (1) | WO2022271818A1 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2023219933A1 (en) * | 2022-05-09 | 2023-11-16 | Entrada Therapeutics, Inc. | Compositions and methods for delivery of nucleic acid therapeutics |
| GB2628421A (en) * | 2023-03-24 | 2024-09-25 | Syntherix Ltd | Peptides and uses thereof |
Family Cites Families (85)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5118800A (en) | 1983-12-20 | 1992-06-02 | California Institute Of Technology | Oligonucleotides possessing a primary amino group in the terminal nucleotide |
| FR2567892B1 (en) | 1984-07-19 | 1989-02-17 | Centre Nat Rech Scient | NOVEL OLIGONUCLEOTIDES, THEIR PREPARATION PROCESS AND THEIR APPLICATIONS AS MEDIATORS IN DEVELOPING THE EFFECTS OF INTERFERONS |
| US4987071A (en) | 1986-12-03 | 1991-01-22 | University Patents, Inc. | RNA ribozyme polymerases, dephosphorylases, restriction endoribonucleases and methods |
| CA1340323C (en) | 1988-09-20 | 1999-01-19 | Arnold E. Hampel | Rna catalyst for cleaving specific rna sequences |
| EP0451221B1 (en) | 1989-08-31 | 1994-10-12 | City Of Hope | Chimeric dna-rna catalytic sequences |
| US5591722A (en) | 1989-09-15 | 1997-01-07 | Southern Research Institute | 2'-deoxy-4'-thioribonucleosides and their antiviral activity |
| ATE269870T1 (en) | 1989-10-24 | 2004-07-15 | Isis Pharmaceuticals Inc | 2'-MODIFIED OLIGONUCLEOTIDES |
| US5646265A (en) | 1990-01-11 | 1997-07-08 | Isis Pharmceuticals, Inc. | Process for the preparation of 2'-O-alkyl purine phosphoramidites |
| US5670633A (en) | 1990-01-11 | 1997-09-23 | Isis Pharmaceuticals, Inc. | Sugar modified oligonucleotides that detect and modulate gene expression |
| GB9009980D0 (en) | 1990-05-03 | 1990-06-27 | Amersham Int Plc | Phosphoramidite derivatives,their preparation and the use thereof in the incorporation of reporter groups on synthetic oligonucleotides |
| EP0745689A3 (en) | 1990-05-11 | 1996-12-11 | Microprobe Corporation | A dipstick for a nucleic acid hybridization assay |
| US6365730B1 (en) | 1990-06-19 | 2002-04-02 | Gene Shears Pty. Limited | DNA-Armed ribozymes and minizymes |
| CA2093664C (en) | 1990-10-12 | 2003-07-29 | Fritz Eckstein | Modified ribozymes |
| DE4216134A1 (en) | 1991-06-20 | 1992-12-24 | Europ Lab Molekularbiolog | SYNTHETIC CATALYTIC OLIGONUCLEOTIDE STRUCTURES |
| EP0538194B1 (en) | 1991-10-17 | 1997-06-04 | Novartis AG | Bicyclic nucleosides, oligonucleotides, their method of preparation and intermediates therein |
| US5359044A (en) | 1991-12-13 | 1994-10-25 | Isis Pharmaceuticals | Cyclobutyl oligonucleotide surrogates |
| US5652094A (en) | 1992-01-31 | 1997-07-29 | University Of Montreal | Nucleozymes |
| FR2687679B1 (en) | 1992-02-05 | 1994-10-28 | Centre Nat Rech Scient | OLIGOTHIONUCLEOTIDES. |
| EP0642589A4 (en) | 1992-05-11 | 1997-05-21 | Ribozyme Pharm Inc | Method and reagent for inhibiting viral replication. |
| EP0577558A2 (en) | 1992-07-01 | 1994-01-05 | Ciba-Geigy Ag | Carbocyclic nucleosides having bicyclic rings, oligonucleotides therefrom, process for their preparation, their use and intermediates |
| JPH07509133A (en) | 1992-07-17 | 1995-10-12 | リボザイム・ファーマシューティカルズ・インコーポレイテッド | Methods and agents for the treatment of animal diseases |
| EP0673559A1 (en) | 1992-12-14 | 1995-09-27 | Honeywell Inc. | Motor system with individually controlled redundant windings |
| DK0691968T3 (en) | 1993-03-30 | 1998-02-23 | Sanofi Sa | Acyclic nucleoside analogs and oligonucleotide sequences containing these |
| DE4311944A1 (en) | 1993-04-10 | 1994-10-13 | Degussa | Coated sodium percarbonate particles, process for their preparation and detergent, cleaning and bleaching compositions containing them |
| US5446137B1 (en) | 1993-12-09 | 1998-10-06 | Behringwerke Ag | Oligonucleotides containing 4'-substituted nucleotides |
| US5519134A (en) | 1994-01-11 | 1996-05-21 | Isis Pharmaceuticals, Inc. | Pyrrolidine-containing monomers and oligomers |
| US5631359A (en) | 1994-10-11 | 1997-05-20 | Ribozyme Pharmaceuticals, Inc. | Hairpin ribozymes |
| US5627053A (en) | 1994-03-29 | 1997-05-06 | Ribozyme Pharmaceuticals, Inc. | 2'deoxy-2'-alkylnucleotide containing nucleic acid |
| US5597909A (en) | 1994-08-25 | 1997-01-28 | Chiron Corporation | Polynucleotide reagents containing modified deoxyribose moieties, and associated methods of synthesis and use |
| WO1996011266A2 (en) | 1994-10-05 | 1996-04-18 | Amgen Inc. | Method for inhibiting smooth muscle cell proliferation and oligonucleotides for use therein |
| US5792747A (en) | 1995-01-24 | 1998-08-11 | The Administrators Of The Tulane Educational Fund | Highly potent agonists of growth hormone releasing hormone |
| US6770748B2 (en) | 1997-03-07 | 2004-08-03 | Takeshi Imanishi | Bicyclonucleoside and oligonucleotide analogue |
| JP3756313B2 (en) | 1997-03-07 | 2006-03-15 | 武 今西 | Novel bicyclonucleosides and oligonucleotide analogues |
| US6794499B2 (en) | 1997-09-12 | 2004-09-21 | Exiqon A/S | Oligonucleotide analogues |
| DE04020014T1 (en) | 1997-09-12 | 2006-01-26 | Exiqon A/S | Bi-cyclic - nucleoside, nucleotide and oligonucleotide analogs |
| US6043352A (en) | 1998-08-07 | 2000-03-28 | Isis Pharmaceuticals, Inc. | 2'-O-Dimethylaminoethyloxyethyl-modified oligonucleotides |
| JP2002535247A (en) | 1998-11-26 | 2002-10-22 | ペンタファルム アクチェンゲゼルシャフト | Transport complex |
| BRPI0008131B8 (en) | 1999-02-12 | 2021-05-25 | Daiichi Sankyo Co Ltd | compound or a salt thereof, oligonucleotide analog, pharmaceutical composition, probe for a gene, initiator to begin amplification, use of an oligonucleotide analog or a pharmacologically acceptable salt thereof, antisense agent, and, antigen agent |
| US7084125B2 (en) | 1999-03-18 | 2006-08-01 | Exiqon A/S | Xylo-LNA analogues |
| PT1178999E (en) | 1999-05-04 | 2007-06-26 | Santaris Pharma As | L-ribo-lna analogues |
| US6525191B1 (en) | 1999-05-11 | 2003-02-25 | Kanda S. Ramasamy | Conformationally constrained L-nucleosides |
| JP4151751B2 (en) | 1999-07-22 | 2008-09-17 | 第一三共株式会社 | New bicyclonucleoside analogues |
| WO2001038547A2 (en) | 1999-11-24 | 2001-05-31 | Mcs Micro Carrier Systems Gmbh | Polypeptides comprising multimers of nuclear localization signals or of protein transduction domains and their use for transferring molecules into cells |
| EP1191097A1 (en) | 2000-09-21 | 2002-03-27 | Leids Universitair Medisch Centrum | Induction of exon skipping in eukaryotic cells |
| JP4387669B2 (en) | 2000-10-13 | 2009-12-16 | ザイジェン エス．アー． | Intracellular delivery of biological effectors with novel transporter peptide sequences |
| US7033597B2 (en) | 2000-10-13 | 2006-04-25 | Université de Lausanne | Intracellular delivery of biological effectors |
| US7569575B2 (en) | 2002-05-08 | 2009-08-04 | Santaris Pharma A/S | Synthesis of locked nucleic acid derivatives |
| US20040219565A1 (en) | 2002-10-21 | 2004-11-04 | Sakari Kauppinen | Oligonucleotides useful for detecting and analyzing nucleic acids of interest |
| EP1562971B1 (en) | 2002-11-05 | 2014-02-12 | Isis Pharmaceuticals, Inc. | Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation |
| CA2524255C (en) | 2003-03-21 | 2014-02-11 | Academisch Ziekenhuis Leiden | Modulation of exon recognition in pre-mrna by interfering with the secondary rna structure |
| ATE555118T1 (en) | 2003-08-28 | 2012-05-15 | Takeshi Imanishi | NEW SYNTHETIC NUCLEIC ACIDS OF THE CROSS-LINKED N-O BOND TYPE |
| US7523096B2 (en) | 2003-12-03 | 2009-04-21 | Google Inc. | Methods and systems for personalized network searching |
| AU2005252662B2 (en) | 2004-06-03 | 2011-08-18 | Isis Pharmaceuticals, Inc. | Double strand compositions comprising differentially modified strands for use in gene modulation |
| US20090312532A1 (en) | 2005-04-22 | 2009-12-17 | Van Deutekom Judith Christina | Modulation of exon recognition in pre-mrna by interfering with the binding of sr proteins and by interfering with secodary rna structure |
| PL1984381T3 (en) | 2006-01-27 | 2011-03-31 | Isis Pharmaceuticals Inc | 6-modified bicyclic nucleic acid analogs |
| EP1986697B1 (en) | 2006-02-17 | 2016-06-29 | GE Healthcare Dharmacon, Inc. | Compositions and methods for inhibiting gene silencing by rna interference |
| WO2007123391A1 (en) | 2006-04-20 | 2007-11-01 | Academisch Ziekenhuis Leiden | Therapeutic intervention in a genetic disease in an individual by modifying expression of an aberrantly expressed gene. |
| EP1857548A1 (en) | 2006-05-19 | 2007-11-21 | Academisch Ziekenhuis Leiden | Means and method for inducing exon-skipping |
| EP2081949B1 (en) | 2006-09-22 | 2014-12-10 | GE Healthcare Dharmacon, Inc. | Tripartite oligonucleotide complexes and methods for gene silencing by rna interference |
| ATE540118T1 (en) | 2006-10-18 | 2012-01-15 | Isis Pharmaceuticals Inc | ANTISENSE COMPOUNDS |
| US20100016215A1 (en) | 2007-06-29 | 2010-01-21 | Avi Biopharma, Inc. | Compound and method for treating myotonic dystrophy |
| HUE028662T2 (en) | 2007-10-26 | 2016-12-28 | Academisch Ziekenhuis Leiden | Means and methods for counteracting muscle disorders |
| EP2119783A1 (en) | 2008-05-14 | 2009-11-18 | Prosensa Technologies B.V. | Method for efficient exon (44) skipping in Duchenne Muscular Dystrophy and associated means |
| PT2417257E (en) | 2009-04-10 | 2016-06-03 | Universität Bern | Tricyclo-dna antisense oligonucleotides, compositions, and methods for the treatment of disease |
| US20110269665A1 (en) * | 2009-06-26 | 2011-11-03 | Avi Biopharma, Inc. | Compound and method for treating myotonic dystrophy |
| US9161948B2 (en) | 2011-05-05 | 2015-10-20 | Sarepta Therapeutics, Inc. | Peptide oligonucleotide conjugates |
| CN104837997A (en) * | 2012-09-25 | 2015-08-12 | 建新公司 | Peptide-linked morpholino antisense oligonucleotides for treatment of myotonic dystrophy |
| US8993233B2 (en) | 2012-12-12 | 2015-03-31 | The Broad Institute Inc. | Engineering and optimization of systems, methods and compositions for sequence manipulation with functional domains |
| KR20150105634A (en) | 2012-12-12 | 2015-09-17 | 더 브로드 인스티튜트, 인코퍼레이티드 | Engineering and optimization of improved systems, methods and enzyme compositions for sequence manipulation |
| US8697359B1 (en) | 2012-12-12 | 2014-04-15 | The Broad Institute, Inc. | CRISPR-Cas systems and methods for altering expression of gene products |
| PT2896697E (en) | 2012-12-12 | 2015-12-31 | Massachusetts Inst Technology | Engineering of systems, methods and optimized guide compositions for sequence manipulation |
| CN110982844B (en) | 2012-12-12 | 2024-08-13 | 布罗德研究所有限公司 | CRISPR-CAS component systems, methods, and compositions for sequence manipulation |
| US20140310830A1 (en) | 2012-12-12 | 2014-10-16 | Feng Zhang | CRISPR-Cas Nickase Systems, Methods And Compositions For Sequence Manipulation in Eukaryotes |
| JP6625055B2 (en) | 2013-12-12 | 2020-01-08 | ザ・ブロード・インスティテュート・インコーポレイテッド | Compositions and methods of using the CRISPR-CAS system in nucleotide repeat disorders |
| US20180344817A1 (en) | 2015-05-01 | 2018-12-06 | Precision Biosciences, Inc. | Precise deletion of chromosomal sequences in vivo and treatment of nucleotide repeat expansion disorders using engineered nucleases |
| EP3359667A1 (en) | 2015-10-05 | 2018-08-15 | ProQR Therapeutics II B.V. | Use of single-stranded antisense oligonucleotide in prevention or treatment of genetic diseases involving a trinucleotide repeat expansion |
| JP6657520B2 (en) | 2016-02-03 | 2020-03-04 | 株式会社神戸製鋼所 | Tire air filling mechanism and tire air filling method of tire testing device |
| KR20170130253A (en) | 2016-05-18 | 2017-11-28 | 에스케이텔레콤 주식회사 | Method for providing of adaptive streaming service and apparatus therefor |
| US10265249B2 (en) | 2016-09-29 | 2019-04-23 | The Procter & Gamble Company | Fibrous structures comprising glyceride copolymers |
| KR20190077568A (en) | 2016-11-16 | 2019-07-03 | 더 리젠츠 오브 더 유니버시티 오브 캘리포니아 | Inhibitors of CRISPR-Cas9 |
| KR20180102871A (en) | 2017-03-08 | 2018-09-18 | 엘지전자 주식회사 | Mobile terminal and vehicle control method of mobile terminal |
| EP3592365A4 (en) | 2017-03-10 | 2021-01-13 | The Board Of Regents Of The University Of Texas System | Treatment of fuchs' endothelial corneal dystrophy |
| EP3755351A4 (en) * | 2018-02-22 | 2021-11-24 | Entrada Therapeutics, Inc. | Compositions and methods for treating mitochondrial neurogastrointestinal encephalopathy |
| GB201812972D0 (en) * | 2018-08-09 | 2018-09-26 | Univ Oxford Innovation Ltd | Cell-penetrating peptides |
| US20230020092A1 (en) * | 2019-12-19 | 2023-01-19 | Entrada Therapeutics, Inc. | Compositions for delivery of antisense compounds |
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| CO2023018002A2 (en) | 2024-02-05 |
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