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miRNA analog modified by locked nucleic acid and thiophosphoric acid and application of miRNA analog in preparation of antitumor drugs

An anti-tumor drug, phosphorothioate technology, applied in the direction of anti-tumor drugs, DNA / RNA fragments, drug combinations, etc., can solve problems such as unsatisfactory results, achieve great potential and application value, promote apoptosis, and enhance anti-bone marrow tumor effect

Inactive Publication Date: 2019-10-22
INST OF HEMATOLOGY & BLOOD DISEASES HOSPITAL CHINESE ACADEMY OF MEDICAL SCI & PEKING UNION MEDICAL COLLEGE
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  • Abstract
  • Description
  • Claims
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AI Technical Summary

Problems solved by technology

However, microRNA analogues are currently limited to small RNA double strands. Although a few microRNA analogues have entered clinical trials, the results are not ideal

Method used

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  • miRNA analog modified by locked nucleic acid and thiophosphoric acid and application of miRNA analog in preparation of antitumor drugs
  • miRNA analog modified by locked nucleic acid and thiophosphoric acid and application of miRNA analog in preparation of antitumor drugs
  • miRNA analog modified by locked nucleic acid and thiophosphoric acid and application of miRNA analog in preparation of antitumor drugs

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Embodiment Construction

[0021] The present invention is further described below in conjunction with embodiment.

[0022] 1. Materials and methods

[0023] 1.1. Cell culture

[0024] Human myeloma cell lines ARP1 and OCI-My5 and human breast cancer cell line MCF7 (MCF7 cell line: purchased from ATCC; ARP1 cell line: University of Iowa, USA; OCI-MY5 cell line: University of Iowa, USA). ARP1 and OCI-My5 use RPMI-1640 complete medium (HyClone TM , Utah, USA), MCF7 was cultured in DMEM (high glucose) complete medium (HyClone TM , Utah, USA) cultured. The complete medium contained 10% fetal bovine serum ( LifeTechnologies) and 1% double antibody ( Life Technologies). All cell lines were cultured at 37°C with 5% carbon dioxide.

[0025] 1.2. Modification of oligodeoxynucleotide and locked nucleic acid

[0026] The MiR-15a gene is located on human chromosome 13. The ODN of miR-15a was named OMM-15a, and it was improved by LNA modification and named LNA-15a. OMM-15a and LNA-15a are both synthesize...

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Abstract

The invention discloses a miRNA analog modified by locked nucleic acid and thiophosphoric acid and application of the miRNA analog in preparation of antitumor drugs. According to the miRNA analog, three nucleic acids of each of the two ends of a DNA single strand of a simulated miR-15a sequence are modified by locked nucleic acid, and phosphoric acid between two nucleotides is modified by thiophosphate. The sequence of the DNA single strand of the simulated miR-15a is SEQ ID: No1. LNA-15a modified by locked nucleic acid can obviously inhibit tumor proliferation and promote tumor cell apoptosis. In vivo experiments also show that LNA-15a can be used as an ideal treatment strategy to well achieve the functions of the simulated miR-15a in vivo, such as tumor cell proliferation inhibition andtumor cell apoptosis promotion, and moreover, LNA-15a can enhance the anti-myeloma effect of BTZ. A theoretical basis is laid for clinical application of the miR-15a analog in anti-tumor treatment.

Description

technical field [0001] The invention relates to the field of biotechnology, in particular to a miRNA analog modified by locked nucleic acid and phosphorothioate and its application in the preparation of antitumor drugs. Background technique [0002] Multiple myeloma (MM) is a common hematologic tumor in middle-aged and elderly people, accounting for about 1% of all malignant tumors and 10% of hematologic malignancies. With the rapid aging of our country, its incidence has shown an obvious upward trend in recent years. At present, MM is still an incurable malignant tumor, and almost all MM will relapse and eventually fail to treat. [0003] MicroRNA is a type of small non-coding RNA, generally composed of 18-24 nucleotides. It can bind to the 3' untranslated region (3'UTR) of target RNA molecules and produce post-transcriptional repression. More and more studies have shown that there is abnormal expression of microRNA in tumor cells, which is closely related to the occurre...

Claims

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Application Information

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IPC IPC(8): C12N15/113A61K31/712A61K31/7125A61P35/00
CPCC12N15/113A61K31/712A61K31/7125A61P35/00C12N2310/141C12N2310/315C12N2310/3231
Inventor 郝牧李忠清邱录贵
Owner INST OF HEMATOLOGY & BLOOD DISEASES HOSPITAL CHINESE ACADEMY OF MEDICAL SCI & PEKING UNION MEDICAL COLLEGE
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