[go: up one dir, main page]

AR133035A1 - COMPOSITIONS AND METHODS FOR INHIBITING THE EXPRESSION OF 3-HYDROXY-3-METHYLGLUTARYL-COA REDUCTASE (HMGCR) - Google Patents

COMPOSITIONS AND METHODS FOR INHIBITING THE EXPRESSION OF 3-HYDROXY-3-METHYLGLUTARYL-COA REDUCTASE (HMGCR)

Info

Publication number
AR133035A1
AR133035A1 ARP240101597A ARP240101597A AR133035A1 AR 133035 A1 AR133035 A1 AR 133035A1 AR P240101597 A ARP240101597 A AR P240101597A AR P240101597 A ARP240101597 A AR P240101597A AR 133035 A1 AR133035 A1 AR 133035A1
Authority
AR
Argentina
Prior art keywords
hmgcr
dsrna
antisense strand
strand
expression
Prior art date
Application number
ARP240101597A
Other languages
Spanish (es)
Inventor
Dongxu Shu
Pengcheng Patrick Shao
Shiwei Xia
Original Assignee
Shanghai Argo Biopharmaceutical Co Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Shanghai Argo Biopharmaceutical Co Ltd filed Critical Shanghai Argo Biopharmaceutical Co Ltd
Publication of AR133035A1 publication Critical patent/AR133035A1/en

Links

Classifications

    • 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
    • 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
    • A61K31/713—Double-stranded nucleic acids or oligonucleotides
    • 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
    • C12N15/1137—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 against enzymes
    • 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
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal 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
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]
    • 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
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/343—Spatial arrangement of the modifications having patterns, e.g. ==--==--==--
    • 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
    • C12N2320/10—Applications; Uses in screening processes
    • C12N2320/11—Applications; Uses in screening processes for the determination of target sites, i.e. of active 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
    • C12N2320/00—Applications; Uses
    • C12N2320/30—Special therapeutic applications
    • C12N2320/32—Special delivery means, e.g. tissue-specific
    • 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
    • C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
    • C12N2750/00011—Details
    • C12N2750/14011—Parvoviridae
    • C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
    • C12N2750/14141—Use of virus, viral particle or viral elements as a vector
    • C12N2750/14143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Biochemistry (AREA)
  • Public Health (AREA)
  • Microbiology (AREA)
  • Biophysics (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Physics & Mathematics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Plant Pathology (AREA)
  • Virology (AREA)
  • Epidemiology (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Abstract

Se proporcionan composiciones y métodos útiles para reducir la expresión del gen de la 3-hidroxi-3-metilglutaril-CoA reductasa (HMGCR) y para el tratamiento de enfermedades y afecciones asociadas a HMGCR. Se proporcionan agentes de ARNbc de HMGCR, agentes polinucleotídicos antisentido de HMGCR, composiciones que comprenden agentes de ARNbc de HMGCR y composiciones que comprenden agentes polinucleotídicos antisentido de HMGCR que pueden usarse para reducir la expresión de HMGCR en células y sujetos. Reivindicación 1: Un agente de ácido ribonucleico bicatenario (ARNbc) para inhibir la expresión de la 3-hidroxi-3-metilglutaril-CoA reductasa (HMGCR), en donde el agente de ARNbc que incluye una cadena sentido y una cadena antisentido, en donde la cadena sentido comprende al menos 15 nucleótidos contiguos que difieren en no más de 3 nucleótidos de la secuencia de nucleótidos de la SEQ ID Nº 1 y la cadena antisentido comprende al menos 15 nucleótidos contiguos que difieren en no más de 3 nucleótidos de la secuencia de nucleótidos de la SEQ ID Nº 2, en donde la cadena sentido y la cadena antisentido pueden ser parcial, sustancial o totalmente complementarias entre sí. Reivindicación 4: Un agente de ácido ribonucleico bicatenario (ARNbc) para inhibir la expresión de la 3-hidroxi-3-metilglutaril-CoA reductasa (HMGCR), en donde el agente de ARNbc comprende una cadena sentido y una cadena antisentido, comprendiendo las posiciones de nucleótidos 2 a 18 en la cadena antisentido una región de complementariedad a un transcrito de ARN de HMGCR, en donde la región de complementariedad comprende al menos 15 nucleótidos contiguos que difieren en 0, 1, 2 o 3 nucleótidos de una de las secuencias antisentido enumeradas en una de las Tablas 1 - 3, y comprendiendo opcionalmente un ligando de direccionamiento. Reivindicación 6: Un agente de ácido ribonucleico bicatenario (ARNbc) para inhibir la expresión de la 3-hidroxi-3-metilglutaril-CoA reductasa (HMGCR), en donde el agente de ARNbc incluye una cadena sentido y una cadena antisentido, en donde la cadena antisentido de ARNbc es sustancialmente o totalmente complementaria a una cualquiera de una región diana de la SEQ ID Nº 1, y preferentemente el agente de ARNbc comprende una secuencia de cadena antisentido expuesta en una cualquiera de las Tablas 1 - 3. Reivindicación 11: Un agente de ácido ribonucleico bicatenario (ARNbc) para inhibir la expresión de la 3-hidroxi-3-metilglutaril-CoA reductasa (HMGCR), en donde el agente de ARNbc incluye una cadena sentido y una cadena antisentido, en donde la cadena sentido es complementaria a la cadena antisentido, en donde la cadena antisentido comprende una región complementaria a parte de un ARNm que codifica HMGCR, en donde cada cadena tiene de aproximadamente 15 a aproximadamente 30 nucleótidos de longitud, en donde la secuencia de cadena sentido puede representarse por la fórmula (1): 5’-(N’L)ₙ’ N’LN’L N’N₁ N’N₂ N’N₃ N’N₄ N’L N’F N’L N’N₅ N’N₆ N’L N’L N’L (N’L)ₘ’-3’ (1) en donde: cada N’F representa un nucleótido modificado con 2’-fluoro; cada N’N₁, N’N₂, N’N₃, N’N₄, N’N₅ y N’N₆ representa independientemente un nucleótido modificado o sin modificar; cada N’L representa independientemente un nucleótido modificado o sin modificar, pero no un nucleótido modificado con 2’-fluoro; y m’ y n’ son cada uno independientemente un número entero de 0 a 7. Reivindicación 39: Una composición que comprende un agente de ARNbc de una cualquiera de las reivindicaciones 1 - 38. Reivindicación 44: Una célula que comprende un agente de ARNbc de una cualquiera de las reivindicaciones 1 - 38, opcionalmente, la célula es una célula de mamífero, opcionalmente una célula humana.Compositions and methods useful for reducing the expression of the 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) gene and for treating diseases and conditions associated with HMGCR are provided. HMGCR dsRNA agents, HMGCR antisense polynucleotide agents, compositions comprising HMGCR dsRNA agents, and compositions comprising HMGCR antisense polynucleotide agents that can be used to reduce the expression of HMGCR in cells and subjects are provided. Claim 1: A double-stranded ribonucleic acid (dsRNA) agent for inhibiting the expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), wherein the dsRNA agent includes a sense strand and an antisense strand, wherein the sense strand comprises at least 15 contiguous nucleotides that differ by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO: 1 and the antisense strand comprises at least 15 contiguous nucleotides that differ by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO: 2, wherein the sense strand and the antisense strand may be partially, substantially, or fully complementary to each other. Claim 4: A double-stranded ribonucleic acid (dsRNA) agent for inhibiting the expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), wherein the dsRNA agent comprises a sense strand and an antisense strand, nucleotide positions 2 to 18 on the antisense strand comprising a region of complementarity to an HMGCR RNA transcript, wherein the region of complementarity comprises at least 15 contiguous nucleotides that differ by 0, 1, 2, or 3 nucleotides from one of the antisense sequences listed in one of Tables 1 - 3, and optionally comprising a targeting ligand. Claim 6: A double-stranded ribonucleic acid (dsRNA) agent for inhibiting the expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), wherein the dsRNA agent includes a sense strand and an antisense strand, wherein the antisense strand of dsRNA is substantially or fully complementary to any one of a target region of SEQ ID NO: 1, and preferably the dsRNA agent comprises an antisense strand sequence set forth in any one of Tables 1 - 3. Claim 11: A double-stranded ribonucleic acid (dsRNA) agent for inhibiting the expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), wherein the dsRNA agent includes a sense strand and an antisense strand, wherein the sense strand is complementary to the antisense strand, wherein the antisense strand comprises a region complementary to part of an mRNA encoding HMGCR, wherein each strand is about 15 to about 30 nucleotides in length, wherein the sense strand sequence can be represented by formula (1): 5’-(N’L)ₙ’ N’LN’L N’N₁ N’N₂ N’N₃ N’N₄ N’L N’F N’L N’N₅ N’N₆ N’L N’L N’L (N’L)ₘ’-3’ (1) wherein: each N’F represents a 2’-fluoro modified nucleotide; each N’N₁, N’N₂, N’N₃, N’N₄, N’N₅ and N’N₆ independently represents a modified or unmodified nucleotide; each N’L independently represents a modified or unmodified nucleotide, but not a 2’-fluoro modified nucleotide; and m’ and n’ are each independently an integer from 0 to 7. Claim 39: A composition comprising a dsRNA agent of any one of claims 1-38. Claim 44: A cell comprising a dsRNA agent of any one of claims 1-38, optionally, the cell is a mammalian cell, optionally a human cell.

ARP240101597A 2023-06-21 2024-06-21 COMPOSITIONS AND METHODS FOR INHIBITING THE EXPRESSION OF 3-HYDROXY-3-METHYLGLUTARYL-COA REDUCTASE (HMGCR) AR133035A1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN2023101548 2023-06-21

Publications (1)

Publication Number Publication Date
AR133035A1 true AR133035A1 (en) 2025-08-20

Family

ID=93934852

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP240101597A AR133035A1 (en) 2023-06-21 2024-06-21 COMPOSITIONS AND METHODS FOR INHIBITING THE EXPRESSION OF 3-HYDROXY-3-METHYLGLUTARYL-COA REDUCTASE (HMGCR)

Country Status (4)

Country Link
AR (1) AR133035A1 (en)
TW (1) TW202500747A (en)
UY (1) UY40801A (en)
WO (1) WO2024260434A1 (en)

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6369103B1 (en) * 1994-01-18 2002-04-09 Bristol-Myers Squibb Company Method for preventing or reducing risk of onset of cardiovascular events employing an HMG CoA reductase inhibitor
US20040006031A1 (en) * 2002-07-02 2004-01-08 Isis Pharmaceuticals Inc. Antisense modulation of HMG-CoA reductase expression
FR2840217B1 (en) * 2002-06-03 2005-06-24 Oreal COSMETIC COMPOSITIONS COMPRISING AT LEAST ONE DOUBLE-STRANDED RNA OLIGONUCLEOTIDE (DSRNA) AND USES THEREOF
EP2336317B1 (en) * 2003-06-13 2019-09-11 Alnylam Europe AG Double-stranded ribonucleic acid with increased effectiveness in an organism
MX2007007283A (en) * 2007-06-15 2009-02-18 World Trade Imp Export Wtie Ag Pharmaceutical composition combining an enzyme hmg-coa reductase inhibiting agent and a gastrointestinal lipase enzyme inhibiting agent.
EP4377458A1 (en) * 2021-07-29 2024-06-05 Alnylam Pharmaceuticals, Inc. 3-hydroxy-3-methylglutaryl-coa reductase (hmgcr) irna compositions and methods of use thereof

Also Published As

Publication number Publication date
UY40801A (en) 2024-12-13
TW202500747A (en) 2025-01-01
WO2024260434A1 (en) 2024-12-26

Similar Documents

Publication Publication Date Title
AU778474B2 (en) Method and medicament for inhibiting the expression of a defined gene
WO2000063364A3 (en) Methods and compositions for inhibiting the function of polynucleotide sequences
WO2006073601A3 (en) Methods and compositions for rna interference
WO2005089287A3 (en) Methods and compositions for the specific inhibition of gene expression by double-stranded rna
BR112022014513A2 (en) CHAOTROPIC AGENTS TO REDUCE DOUBLE-STRAND RNA FORMATION
RU2011124146A (en) COMPOSITIONS AND METHODS OF SUPPRESSING EXPRESSION OF FACTOR VII GENES
US10612020B2 (en) Artificial mimic miRNA for controlling gene expression, and use of same
AR123420A1 (en) DUX4 INHIBITORS AND METHODS OF USE THEREOF
JP2022078058A (en) Genome editing method
Brinkman et al. Nucleoside analogs in ADAR guide strands targeting 5′-UA [combining low line] sites
Yu et al. Comprehensive analysis of miRNA profiles reveals the role of Schistosoma japonicum miRNAs at different developmental stages
MX2025010451A (en) Compositions and methods for inhibition of expression of inhibin subunit beta e (inhbe) genes
AR133035A1 (en) COMPOSITIONS AND METHODS FOR INHIBITING THE EXPRESSION OF 3-HYDROXY-3-METHYLGLUTARYL-COA REDUCTASE (HMGCR)
Wang et al. Testis brain ribonucleic acid-binding protein/translin possesses both single-stranded and double-stranded ribonuclease activities
MX2025006656A (en) Antisense oligonucleotides for the treatment of cardiovascular disease
WO2021262919A3 (en) 5-halouracil-modified micrornas and their use in the treatment of cancer
Kang et al. Optimization of double‐stranded RNAi intrathoracic injection method in Aedes aegypti
WO2024211376A3 (en) Compositions and methods for treating cag repeat diseases
AR131145A1 (en) Antisense oligonucleotides for the treatment of hereditary hemochromatosis (HFE)
KR101181728B1 (en) siRNA inhibiting expression of rpS3 in cells
KR20210120034A (en) Antisense drug against human intracellular adhesion molecule 1 (ICAM-1)
Priyadarshini et al. Downregulation of ribosomal RNA (rRNA) genes in human head and neck squamous cell carcinoma (HNSCC) cells is linked to rDNA promoter hypermethylation
AR126265A1 (en) COMPOSITIONS AND METHODS TO SILENCE MYOC EXPRESSION
US10351855B2 (en) Pharmaceutical composition for inhibition of cancer cell metastasis including siRNA for ribosomal protein S3
CN114787350A (en) mRNA and method for producing same, apparatus for producing protein, and method for producing protein