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A siRNA targeting and inhibiting the expression of sos1 gene and its application

A gene expression and targeting technology, applied in the field of siRNA, can solve the problems of drug resistance in patients, achieve the effects of inhibiting growth, increasing drug sensitivity, and overcoming drug resistance

Active Publication Date: 2022-02-01
JINAN UNIVERSITY
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Problems solved by technology

However, only a small number of patients treated with imatinib achieved complete remission, the remaining 20% ​​of patients discontinued the drug due to drug intolerance, and another 20% developed drug resistance that limited its use
Although, the newly marketed TKIs in recent years, such as nilotinib, dasatinib, bosutinib and ponatinib, provide a variety of options for CML patients, and these new drugs show stronger Efficacy, but still failed to solve the problem of drug resistance in patients

Method used

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  • A siRNA targeting and inhibiting the expression of sos1 gene and its application
  • A siRNA targeting and inhibiting the expression of sos1 gene and its application
  • A siRNA targeting and inhibiting the expression of sos1 gene and its application

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Embodiment 1

[0025] 1. Materials and methods

[0026] 1. Materials

[0027] 1.1 Cells and animals

[0028] K562, KCL-22 (human chronic myelogenous leukemia line), purchased from the Shanghai Cell Bank of the Chinese Academy of Sciences, BV173 (human peripheral blood B-cell leukemia line), donated to the American Institute of Hematology, can also be obtained from commercial channels. KU812 (human chronic myelogenous leukemia) was donated to Pan Jingxuan's research group at Jinan University, and can also be obtained from commercial channels. Balb / cnude mice aged 4-6 weeks were purchased from Beijing Weitong Lihua Experimental Animal Technology Co., Ltd.

[0029] 1.2 Reagents

[0030] 1640 medium, opti-MEM medium, anti-SOS1 (mouse SOS1 monoclonal antibody) (santa), anti-β-actin (rabbit β-actin monoclonal antibody) (CST), siRNA lyophilized powder (Sharp Biomake), CCK-8 (biomake), imatinib (STI571) (selleck), lipo2000 (thermo), qPCR reagent (biomake).

[0031] 1.3 Random sequence RNA doubl...

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Abstract

The invention discloses a siRNA for targeting and inhibiting the expression of SOS1 gene and its application. The sequence of the siRNA is: sense strand: 5′-GCAGAATCTTCACCATCTA-3′; antisense strand: 5′-TAGATGGTGAAGATTCTGC-3′. The present invention screens out the effective siRNA sequence of SOS1, SOS1-siRNA#3, by detecting the expression level changes of SOS1 mRNA level and protein level, which can effectively inhibit the proliferation ability and clone formation ability of CML cells, and effectively inhibit transplanted tumors in animals growth, while increasing the drug sensitivity of CML cells to imatinib. Therefore, SOS1 is a potential new target for the treatment of chronic myelogenous leukemia, and SOS1‑siRNA has potential value in overcoming imatinib resistance.

Description

technical field [0001] The present invention relates to an siRNA, in particular to an siRNA targeting to inhibit the expression of SOS1 gene and its application. Background technique [0002] Chronic myelogenous leukemia (CML) is a characteristic genetic abnormality. The ph chromosome is its characteristic cytogenetic marker, namely t(9;22)(q34;ql1), and there is a specific BCR-ABL fusion gene. A disorder that causes malignant clonal proliferation of hematopoietic stem cells. As the first generation of tyrosine kinase inhibitors targeting the P210 protein encoded by the BCR-ABL fusion gene, imatinib has revolutionized the treatment of chronic granulocytes. However, only a small number of patients treated with imatinib achieved complete remission, the remaining 20% ​​of patients discontinued the drug due to drug intolerance, and another 20% of patients developed drug resistance that limited use. Although, the newly marketed TKIs in recent years, such as nilotinib, dasatinib...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12N15/113A61K31/713A61P35/02
CPCC12N15/113A61K31/713A61P35/02C12N2310/141
Inventor 费嘉刘燕君
Owner JINAN UNIVERSITY
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