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WO2024065900A1 - Arnsi pour inhiber la croissance tumorale et son utilisation - Google Patents

Arnsi pour inhiber la croissance tumorale et son utilisation Download PDF

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WO2024065900A1
WO2024065900A1 PCT/CN2022/126237 CN2022126237W WO2024065900A1 WO 2024065900 A1 WO2024065900 A1 WO 2024065900A1 CN 2022126237 W CN2022126237 W CN 2022126237W WO 2024065900 A1 WO2024065900 A1 WO 2024065900A1
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seq
cancer
sirna
group
tumor
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Chinese (zh)
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许强
王冠
魏金旺
王堃
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Genomicare Biotechnology (shanghai) Co Ltd
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Genomicare Biotechnology (shanghai) Co Ltd
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    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • C07H21/02—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical
    • 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

Definitions

  • the invention relates to a method for inhibiting tumor cell growth by targeting AURKB with allele-specific siRNA, as well as siRNA for inhibiting tumor growth and application thereof.
  • Cancer is one of the leading causes of death in the world. As a populous country in the world, China's cancer data is not optimistic. Whether it is the number of new cases or deaths, China far exceeds other countries and ranks first in the world. In 2022, it is estimated that there will be about 4,820,000 newly diagnosed cancer cases and about 3,210,000 deaths in China. The increasing number of new cases and deaths has prompted my country to need more cancer prevention and treatment interventions to reduce the burden of cancer in the future.
  • Single nucleotide polymorphism refers to a DNA sequence polymorphism caused by a variation in a single nucleotide position on a chromosome sequence, and the frequency of occurrence in the population is greater than 1%.
  • the two genotypes containing SNP are alleles.
  • Tumor cells often have loss of heterozygosity (LOH), which means that tumor cells with LOH can only rely on one of the genotypes. If the gene that has LOH is also an essential gene, we can specifically inhibit the expression of this genotype, thereby killing tumor cells, while normal cells, since LOH does not occur, can still rely on the other genotype to normally express the essential gene without being affected.
  • LOH heterozygosity
  • AURKB is a mitotic serine/threonine protein kinase that belongs to the Aurora kinase family. Aurora kinase was discovered in 1995, but it was not until 1998 that it was first applied to the observation of human cancer tissue expression. During mitosis, Aurora kinase is involved in spindle formation, centrosome maturation, chromosome differentiation and cytokinesis. AURKB is a member of the chromosome passenger protein complex and plays an important role in cell cycle progression. Dysregulation of AURKB has been observed in some tumors. The gene is highly expressed in a variety of tumors and is associated with tumor cell invasion, metastasis and drug resistance.
  • AURKB Aurora kinase B
  • siRNA Small interfering RNA
  • mRNA messenger ribonucleotides
  • RISC RNA-induced silencing complex
  • the present invention provides a siRNA that can specifically target the expression of the AURKB gene of a specific genotype, thereby achieving the purpose of eliminating tumor cells without affecting the function of normal cells.
  • the siRNA designed according to the SNP of the present invention can specifically inhibit and kill tumor cells that have LOH, while the growth of heterozygous cells (representing normal cells) is not significantly affected. Therefore, this area can become a new siRNA drug targeting area for inhibiting tumor growth, thereby achieving the goals of the siRNA drug of the present invention, such as good specificity, high efficiency, easy development, and reusability.
  • the purpose of the present invention is to solve the problem of insufficient specificity of small molecule inhibitors and obvious side effects of medication at this stage.
  • siRNAs By designing different siRNAs to target the two haplotype sequences of the AURKB gene respectively, tumor cells expressing the haplotype can be specifically inhibited, thereby reducing the impact on heterozygous normal cells. This can solve the problem of high toxicity caused by the inability of small molecule AURKB inhibitors to distinguish genotypes.
  • the two SNPs in the two haplotypes H1 (CGTGCCCAT) (SEQ ID NO: 45) and H2 (AGTGCCCAG) (SEQ ID NO: 46) are only 7bp apart. Therefore, this region is very suitable as a siRNA targeting region, which can improve the specificity of siRNA, thereby inhibiting the growth of tumor cells with heterozygous loss.
  • small interfering nucleic acid As used herein, the terms “small interfering nucleic acid,” “siNA or SINA” molecule, “small interfering RNA,” “siRNA,” “small interfering nucleic acid molecule,” “small interfering oligonucleotide molecule” refer to any nucleic acid molecule that is capable of inhibiting or downregulating gene expression through the RNA interference mechanism.
  • target sequence refers to a continuous portion of the nucleotide sequence of an mRNA molecule (including messenger RNA (mRNA), which is a product of RNA processing primary transcript products) formed during transcription of the H1/H2 gene.
  • mRNA messenger RNA
  • the target portion of the sequence will be at least long enough to serve as a substrate for siRNA to guide cutting in this portion or its vicinity.
  • the target sequence will generally be from 9-36 nucleotides in length, for example, 15-30 nucleotides in length, including all subranges therebetween.
  • the target sequence can have from 15-30 nucleotides, 15-26 nucleotides, 15-23 nucleotides, 15-22 nucleotides, 15-21 nucleotides, 15-20 nucleotides, 15-19 nucleotides, 15-18 nucleotides, 15-17 nucleotides, 18-30 nucleotides, 18-26 nucleotides, 18-23 nucleotides, 18-22 nucleotides, 18-21 nucleotides, 18-20 nucleotides, 19-30 nucleotides, 19-26 nucleotides, 19-23 nucleotides, 19-22 nucleotides, 19-21 nucleotides, 19-20 nucleotides, 20-30 nucleotides, 20-26 nucleotides, 20-25 nucleotides, 20-24 nucleotides, 20-23 nucleotides, 20-22 nucleotides, 20-21 nucleotides, 21-30 nucleotides, 21-
  • RNA refers to a molecule comprising at least one ribonucleotide residue, including double-stranded RNA, single-stranded RNA, isolated RNA, partially purified, pure or synthetic RNA, recombinantly produced RNA, and altered RNA or analogs of naturally occurring RNA.
  • RNA refers to an iRNA comprising an RNA molecule or a molecular complex having a hybrid duplex region comprising two antiparallel and substantially complementary nucleic acid strands, which are referred to as having "sense” and “antisense” orientations relative to the target RNA.
  • the duplex region can have any length that allows for specific degradation of the desired target RNA via the RISC pathway, but will generally range from 9 to 36 base pairs in length, e.g., 15-30 base pairs in length. For a duplex between 9 and 36 base pairs, the length of the duplex region is preferably 15-30 base pairs.
  • the duplex can have any length within this range, for example, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 and any subranges therebetween, including but not limited to 15-30 base pairs, 15-26 base pairs, 15-23 base pairs, 15-22 base pairs, 15-21 base pairs, 15-20 base pairs, 15-19 base pairs, 15-18 base pairs, 15-17 base pairs, 18-30 base pairs, 1 22 base pairs, 20-21 base pairs, 21-30 base pairs, 21-26 base pairs, 21-25 base pairs, 21-24 base pairs, 21-23 base pairs, or 21-22 base pairs.
  • dsRNAs produced by processing in cells with Dicer and similar enzymes typically have a base pair length ranging from 19 to 22.
  • One chain of the duplex region of dsDNA contains a sequence that is substantially complementary to the region of the target RNA.
  • the two chains forming the duplex structure can be from a single RNA molecule having at least one self-complementary region, or can be formed by two or more independent RNA molecules.
  • the duplex region is composed of two chains of a single molecule, the molecule can have a duplex region separated by a single nucleotide chain (referred to herein as a "hairpin loop") between the 3'-end of one chain forming the duplex structure and the 5'-end of the corresponding other chain.
  • the hairpin loop can include at least one non-paired nucleotide; in some embodiments, the hairpin loop can include at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 20, at least 31 or more non-paired nucleotides.
  • the two substantially complementary chains of dsRNA are composed of separate RNA molecules, these molecules do not need to be covalently linked, but can be covalently linked.
  • the connecting structure is referred to as a "joint".
  • siRNA is also used herein to refer to dsRNA as described above.
  • the term "inhibit" means that the expression of a gene, or the level of an RNA molecule or equivalent RNA molecule encoding one or more proteins or protein subunits, or the activity of one or more protein subunits is upregulated or downregulated, so that the expression, level or activity is greater or less than that observed when the regulator is not present.
  • the expression of the AURKB gene is inhibited by at least about 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45% or 50% by administering the siRNA characterized in the present invention.
  • the AURKB gene is inhibited by at least about 60%, 70% or 80% by administering the siRNA described herein.
  • the AURKB gene is inhibited by at least about 85%, 90%, 95%, 98%, 99%, or more by administering the siRNA described herein.
  • gene refers to a nucleic acid encoding an RNA sequence, including but not limited to a structural gene encoding a polypeptide.
  • siRNA double-stranded RNA
  • mRNA small RNA
  • DNAi deoxyribonucleic acid interference
  • shRNA small hairpin RNA
  • the present invention relates to a siRNA targeting an mRNA fragment encoded by a sequence shown in SEQ ID NO: 45 or SEQ ID NO: 46.
  • At least one chain consists of a nucleotide chain with a length of 19-30 nucleotides, preferably a nucleotide chain with a length of 19-29, 19-28, 19-27, 19-26, or 19-25 nucleotides.
  • the siRNA comprises at least one modified nucleotide.
  • At least one of the modified nucleotides is selected from the group consisting of a 2'-O-methyl modified nucleotide, a nucleotide comprising a 5'-phosphorothioate group, a terminal nucleotide linked to a cholesteryl derivative or a dodecanoic acid bisdecylamide group.
  • At least one of the modified nucleotides is selected from the group consisting of 2'-deoxy modified nucleotides, locked nucleotides, non-basic nucleotides, 2'-amino modified nucleotides, 2'-alkyl modified nucleotides, morpholino nucleotides, phosphoramidate nucleotides and nucleotides containing non-natural bases.
  • At least one strand of the siRNA comprises a 3' overhang of at least one nucleotide.
  • each strand of the siRNA is modified with a pendant base.
  • the overhanging bases consist of any one or more deoxyribonucleotides selected from dA, dT, dG, and dC.
  • the overhanging bases consist of any two deoxyribonucleotides selected from dA, dT, dG, and dC.
  • the siRNA has a structure selected from the group consisting of: SEQ ID NO: 1 and SEQ ID NO: 2; SEQ ID NO: 3 and SEQ ID NO: 4; SEQ ID NO: 5 and SEQ ID NO: 6; SEQ ID NO: 7 and SEQ ID NO: 8; SEQ ID NO: 9 and SEQ ID NO: 10; SEQ ID NO: 11 and SEQ ID NO: 12; SEQ ID NO: 13 and SEQ ID NO: 14; SEQ ID NO: 15 and SEQ ID NO: 16; SEQ ID NO: 17 and SEQ ID NO: 18; SEQ ID NO: 19 and SEQ ID NO: 20; SEQ ID NO: 21 and SEQ ID NO: 22 No.: SEQ ID NO: 39 and SEQ ID NO: 40; SEQ ID NO: 41 and SEQ ID NO: 42; and SEQ ID NO: 43 and SEQ ID NO: 44.
  • the second aspect of the present invention relates to a vector comprising the siRNA as described in the first aspect of the present invention.
  • the third aspect of the present invention relates to a cell comprising the siRNA as described in the first aspect of the present invention.
  • the present invention relates to a pharmaceutical composition for inhibiting tumor growth, comprising the siRNA as described in the first aspect of the present invention and a pharmaceutically acceptable excipient.
  • the tumor is selected from the group consisting of: glioma, leukemia, brain cancer, esophageal cancer, gastric cancer, lung cancer, liver cancer, bladder cancer, pancreatic cancer, cervical cancer, head and neck cancer, ovarian cancer, melanoma, lymphoma, breast cancer, intestinal cancer, nasopharyngeal cancer, endometrial cancer, and prostate cancer.
  • the tumor is selected from the group consisting of brain cancer, lung cancer and liver cancer.
  • the present invention relates to a pharmaceutical composition for inhibiting tumor growth, comprising siRNA for inhibiting AURKB expression and a pharmaceutically acceptable excipient.
  • the tumor is selected from the group consisting of: glioma, leukemia, brain cancer, esophageal cancer, gastric cancer, lung cancer, liver cancer, bladder cancer, pancreatic cancer, cervical cancer, head and neck cancer, ovarian cancer, melanoma, lymphoma, breast cancer, intestinal cancer, nasopharyngeal cancer, endometrial cancer, and prostate cancer.
  • the tumor is selected from the group consisting of brain cancer, lung cancer and liver cancer.
  • the present invention relates to a method for reducing the expression of AURKB in target cells, wherein the method is performed by administering the siRNA described in the first aspect of the present invention.
  • the present invention relates to a method for inhibiting tumor growth, which is carried out by administering siRNA to a subject in need thereof, wherein the siRNA targets an mRNA fragment encoded by a sequence shown in SEQ ID NO: 45 or SEQ ID NO: 46.
  • At least one strand of the siRNA consists of a nucleotide chain of 19-30 nucleotides, preferably a nucleotide chain of 19-29, 19-28, 19-27, 19-26, or 19-25 nucleotides in length.
  • the siRNA comprises at least one modified nucleotide.
  • each strand of the siRNA is modified with a pendant base.
  • the overhanging bases consist of any one or more deoxyribonucleotides selected from dA, dT, dG, and dC.
  • the overhanging bases consist of any two deoxyribonucleotides selected from dA, dT, dG, and dC.
  • the siRNA has a structure selected from the group consisting of: SEQ ID NO: 1 and SEQ ID NO: 2; SEQ ID NO: 3 and SEQ ID NO: 4; SEQ ID NO: 5 and SEQ ID NO: 6; SEQ ID NO: 7 and SEQ ID NO: 8; SEQ ID NO: 9 and SEQ ID NO: 10; SEQ ID NO: 11 and SEQ ID NO: 12; SEQ ID NO: 13 and SEQ ID NO: 14; SEQ ID NO: 15 and SEQ ID NO: 16; SEQ ID NO: 17 and SEQ ID NO: 18; SEQ ID NO: 19 and SEQ ID NO: 20; SEQ ID NO: 21 and SEQ ID NO: 22 No.: SEQ ID NO: 39 and SEQ ID NO: 40; SEQ ID NO: 41 and SEQ ID NO: 42; and SEQ ID NO: 43 and SEQ ID NO: 44.
  • the tumor is selected from the group consisting of: glioma, leukemia, brain cancer, esophageal cancer, gastric cancer, lung cancer, liver cancer, bladder cancer, pancreatic cancer, cervical cancer, head and neck cancer, ovarian cancer, melanoma, lymphoma, breast cancer, intestinal cancer, nasopharyngeal cancer, endometrial cancer, and prostate cancer.
  • the tumor is selected from the group consisting of brain cancer, lung cancer and liver cancer.
  • the present invention relates to a method for inhibiting tumor growth, comprising administering siRNA that inhibits AURKB expression to a subject in need thereof.
  • the tumor is selected from the group consisting of: glioma, leukemia, brain cancer, esophageal cancer, gastric cancer, lung cancer, liver cancer, bladder cancer, pancreatic cancer, cervical cancer, head and neck cancer, ovarian cancer, melanoma, lymphoma, breast cancer, intestinal cancer, nasopharyngeal cancer, endometrial cancer, and prostate cancer.
  • the tumor is selected from the group consisting of brain cancer, lung cancer and liver cancer.
  • the present invention relates to the use of siRNA in the preparation of a drug for inhibiting tumor growth, wherein the siRNA targets an mRNA fragment encoded by a sequence shown in SEQ ID NO: 45 or SEQ ID NO: 46.
  • At least one strand of the siRNA consists of a nucleotide chain of 19-30 nucleotides, preferably a nucleotide chain of 19-29, 19-28, 19-27, 19-26, or 19-25 nucleotides in length.
  • the siRNA comprises at least one modified nucleotide.
  • each strand of the siRNA is modified with a pendant base.
  • the overhanging bases consist of any one or more deoxyribonucleotides selected from dA, dT, dG, and dC.
  • the overhanging bases are composed of any two deoxyribonucleotides selected from dA, dT, dG, and dC.
  • the siRNA has a structure selected from the group consisting of: SEQ ID NO: 1 and SEQ ID NO: 2; SEQ ID NO: 3 and SEQ ID NO: 4; SEQ ID NO: 5 and SEQ ID NO: 6; SEQ ID NO: 7 and SEQ ID NO: 8; SEQ ID NO: 9 and SEQ ID NO: 10; SEQ ID NO: 11 and SEQ ID NO: 12; SEQ ID NO: 13 and SEQ ID NO: 14; SEQ ID NO: 15 and SEQ ID NO: 16; SEQ ID NO: 17 and SEQ ID NO: 18; SEQ ID NO: 19 and SEQ ID NO: 20; SEQ ID NO: 21 and SEQ ID NO: 22 No.: SEQ ID NO: 39 and SEQ ID NO: 40; SEQ ID NO: 41 and SEQ ID NO: 42; and SEQ ID NO: 43
  • the tumor is selected from the group consisting of: glioma, leukemia, brain cancer, esophageal cancer, gastric cancer, lung cancer, liver cancer, bladder cancer, pancreatic cancer, cervical cancer, head and neck cancer, ovarian cancer, melanoma, lymphoma, breast cancer, intestinal cancer, nasopharyngeal cancer, endometrial cancer, and prostate cancer.
  • the tumor is selected from the group consisting of brain cancer, lung cancer and liver cancer.
  • AURKB is an essential gene in many tumors.
  • a CAS-9 value less than 0 indicates inhibition of tumor growth, and a value less than -3 indicates that tumor cells die rapidly after gene knockout, indicating that the gene is an essential gene.
  • Figure 2 Compared with the expression in normal tissues, AURKB expression was significantly upregulated in liver cancer, lung cancer, and brain glioma;
  • Figure 3 Patients with high AURKB expression in multiple cancer types have poor overall survival prognosis.
  • Figure 3A shows Lingxing data;
  • Figure 3B shows TCGA data;
  • FIG. 4 The newly discovered siRNA targetable region in the AURKB (NM_004217) gene is located between 8205000-8205040 on chromosome 17 (GRCh38.p14, NC_000017.11). The boxed positions are two SNP sites contained in this region;
  • FIGS 5A-5C siRNA transfection results
  • FIG. 6 Cell viability test results using the Cell Titer-Glo (CTG) method.
  • Example 1 AURKB is an essential gene for multiple tumors
  • AURKB is an essential gene (included in the Achilles_common_essentials essential gene list).
  • the CRISPR scores were all negative and basically less than -2 ( Figure 1). Therefore, the AURKB gene is an essential gene in many tumors (such as hepatocellular carcinoma, lung cancer and brain cancer, etc.).
  • Example 2 In liver cancer, lung cancer, and brain cancer, AURKB expression is upregulated in tumor tissues
  • TCGA data show that the expression of AURKB in liver cancer and lung cancer is higher than that in normal tissues.
  • Select the AURKB gene in the public website GEPIA2 http://gepia2.cancer-pku.cn/#analysis), select the corresponding cancer type, and then select Box Plot.
  • the webpage can display the expression comparison chart of the AURKB gene in tumor and normal tissues. Compared with the expression in normal tissues, the expression of AURKB in liver cancer, lung cancer, and brain glioma is significantly upregulated. This indicates that AURKB is closely related to tumor occurrence ( Figure 2).
  • Example 3 GC and TCGA data show that patients with low AURKB expression in hepatocellular carcinoma, lung cancer and brain cancer have better overall survival
  • siRNA haplotypes were found in the AURKB exons.
  • the newly discovered siRNA targetable region in the AURKB (NM_004217) gene is located between 8205000-8205040 on chromosome 17 (GRCh38.p14, NC_000017.11). This region is a completely new siRNA targeting region (Figure 4). The results showed that two SNPs 7 bp apart can significantly improve the inhibition efficiency of siRNA.
  • siRNAs Based on the targeted region and SNP information, a series of siRNAs that can cover the two genotypes were designed and transfection experiments were carried out to observe their interference efficiency.
  • siRNAs designed for this region were screened to obtain the following siRNAs with good knockdown efficiency, as shown in Table 2, which are a series of siRNA sequences designed for haplotype H1 (CGTGCCCAT) (SEQ ID NO.45); as shown in Table 3, which are a series of siRNA sequences designed for haplotype H2 (AGTGCCCAG) (SEQ ID NO.46).
  • hepatocellular carcinoma cell lines were selected to represent three common genotypes: HepG2 (H1 type), Huh-6 (heterozygous, including two genotypes, H1 and H2) and SNU387 (H2 type).
  • the three cell lines were transfected with siRNAs in Tables 3 and 4, as well as negative control siRNA (Reibo Bio) and positive control siRNA (Reibo Bio).
  • Lipofectamine TM RNAiMAXP Thermo Fisher Scientific
  • siRNAs si-1# and si-2# targeting H1 type have the best interference efficiency in HepG2 cells carrying H1, which can inhibit 60% of gene expression, while the rest, such as si-5#, si-6#, si-7#, si-8# and si-11#, can achieve 40% inhibition efficiency.
  • the inhibition efficiency of si-1# and si-2# in the heterozygous Huh-6 carrying H1 and H2 was 50%, and it could only inhibit about 20% in SNU387 carrying H2.
  • si-A6# could inhibit about 40% of the gene expression in SNU387, while the inhibition rate became worse in HepG2 and Huh6.
  • the experimental results confirmed the specific inhibition of siRNA on the expression of different genotypes.
  • siRNA targeting this region can effectively inhibit the expression of AURKB gene in tumor cells and inhibit tumor growth, but has no effect on the growth of hybrid cells
  • siRNAs were selected for the CellTiter-Glo (CTG) growth experiment to observe the effect of AURKB interference on the growth of each cell.
  • the experimental steps refer to the method recommended in the CellTiter-Glo manual, and the cells were tested on days 1, 2, 3, and 4 after transfection.
  • the results are shown in Figure 6.
  • si-1# and si-2# can significantly inhibit the growth of HepG2 carrying H1 type
  • si-A6# significantly inhibits the growth of the cell line SNU387 carrying H2 type, but in the heterozygous cell line Huh-6, the three siRNAs cannot significantly affect cell growth.
  • the experimental results show that targeting the region described in this patent can specifically inhibit tumor growth.
  • siRNA can effectively inhibit the expression of the AURKB gene and inhibit the growth of tumor cells.
  • siRNA does not affect their normal growth.

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Abstract

L'invention concerne un ARNsi pour inhiber la croissance tumorale et son utilisation. L'ARNsi cible un fragment d'ARNm codé par une séquence représentée dans SEQ ID NO : 45 ou SEQ ID NO : 46. L'invention concerne également un procédé d'utilisation de l'ARNsi pour inhiber la croissance tumorale.
PCT/CN2022/126237 2022-09-26 2022-10-19 Arnsi pour inhiber la croissance tumorale et son utilisation Ceased WO2024065900A1 (fr)

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REN, LIRONG: "Effect of Silencing Aurora B via RNAi on Proliferation and Cell Cycle of Ovary Cancer Cell Line A2780", ACTA MEDICINAE UNIVERSITATIS SCIENTIAE ET TECHNOLOGIAE HUAZHONG, HUAZHONG KEJI DAXUE, TONGJI YIXUEYUAN, CN, vol. 40, no. 3, 30 June 2011 (2011-06-30), CN , pages 304 - 309, XP009554366, ISSN: 1672-0741, DOI: 10.3870/j.issn.1672-0741.2011.03.013 *

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