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Antisense nucleic acid medicine composition with bcr3/abl2 and VEGF gene function inhibition and use thereof

An antisense nucleic acid and gene function technology, which is applied in the field of preparation of drugs for the treatment of leukemia, can solve the problems of human normal cytotoxicity and lack of specificity, and achieve the prevention of drug resistance of tumor drug-resistant cells, strong specificity, and reduced Effects of Drug Dose and Toxicity

Inactive Publication Date: 2006-11-29
TAIDA RES CENT OF LIFE SCI & TECH INST OF HEMATOLOGY CHINES
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Problems solved by technology

Traditional chemotherapeutic drugs use transcriptional inhibition or DNA damage as the mechanism of action, lack of specificity, and have severe toxic effects on normal human cells

Method used

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  • Antisense nucleic acid medicine composition with bcr3/abl2 and VEGF gene function inhibition and use thereof
  • Antisense nucleic acid medicine composition with bcr3/abl2 and VEGF gene function inhibition and use thereof
  • Antisense nucleic acid medicine composition with bcr3/abl2 and VEGF gene function inhibition and use thereof

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Embodiment Construction

[0021] Below in conjunction with accompanying drawing and specific embodiment the present invention is described in further detail:

[0022] 1. Design and synthesis of ASO

[0023] ① Thio-modified bcr3 / abl2 antisense oligonucleotides (ASO-b / a) are complementary to 9 nucleotides on both sides of the bcr3 / abl2 fusion point (Skorski T, Szczylick C, Malaguamera L, et al. Folia Histochem Cytobiol, 1991, 29: 85-89), the sequence is: 5'-GAAGGGCTTTTGAACTCT-3'.

[0024] ②Antithio-modified VEGF antisense oligonucleotide (ASO-V) is complementary to the third exon of VEGF mRNA (Li XM, Tang ZY, Zhou G, et al.J Exp Clin Cancer Res, 1998, 17 : 1-3), the sequence is: 5'-GCAGTAGCTGCGCTGATAGTGC-3'.

[0025] ③ The sequence of the irrelevant antisense oligonucleotide (N-ODN) is: 5'-CATTTCTTGCTCTCCACG-3', which has no homology with human genes including bcr / abl and VEGF genes after searching by computer.

[0026] 2. Cell culture and transfection

[0027] The K562 cell line is a cell line deriv...

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Abstract

A composite antisense nucleic acid medicine able to suppress the function of bcr3 / abl2 and VEGF genes features that the fusion gene bcr / abl and the vascular endothelial growth factor (VEGF) are its target and the antisense oligonucleotides (AS-ODNs) of said genes are acting on K562 cell line and k562 transfer tumor. It can be used to prepare the medicine for the pharmacotherapy and gene therapy of chronic granulocyte leukemia, and increasing the sensitivity of leukemia cells to chemicotherapeutic medicine.

Description

technical field [0001] The invention relates to an antisense nucleic acid, in particular to an antisense nucleic acid pharmaceutical composition for chronic myelogenous leukemia fusion gene bcr3 / abl2 and vascular endothelial growth factor VEGF and its application in preparing medicines for treating leukemia. Background technique [0002] Chronic myelogenous leukemia (CML) is a clonal disease of the hematopoietic system, and its characteristic Ph chromosome and the resulting bcr / abl fusion gene and its encoded protein are the pathogenesis of CML. It has been confirmed that in CML, the expression of bcr / abl gene can inhibit the apoptosis of CML cells, which is the main reason for the clonal proliferation of leukemia in patients. As a major pro-angiogenic factor, VEGF binds to specific receptors, can induce the proliferation and migration of vascular endothelial cells in vitro, and can promote angiogenesis in vivo. VEGF plays an important role in the occurrence, development an...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K48/00A61P35/00
Inventor 韩忠朝丛秀丽
Owner TAIDA RES CENT OF LIFE SCI & TECH INST OF HEMATOLOGY CHINES
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