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CN-121987796-A - Application of GABRD gene expression inhibitor in preparation of medicines for treating hepatocellular carcinoma

CN121987796ACN 121987796 ACN121987796 ACN 121987796ACN-121987796-A

Abstract

The invention belongs to the technical field of biological medicines, and particularly relates to application of GABRD gene expression inhibitor in preparation of medicines for treating hepatocellular carcinoma. The GABRD gene expression inhibitor is an adeno-associated virus AAV recombinant vector, WP1066 or IL-10R1 neutralizing antibody for targeted inhibition of GABRD gene expression. The experiments of the invention show that all three GABRD gene expression inhibitors can obviously inhibit the tumor growth of the hepatocellular carcinoma tumor mice.

Inventors

  • WANG CHAOQUN
  • ZHENG LU
  • WU KE
  • WANG CAN
  • HUANG CHENGCHENG

Assignees

  • 中国人民解放军陆军军医大学第二附属医院

Dates

Publication Date
20260508
Application Date
20260326

Claims (8)

  1. Use of a gabrd gene expression inhibitor in the manufacture of a medicament for treating hepatocellular carcinoma, GABRD gene expression inhibitor selected from any one of the following (i) to (iii): (i) The GABRD gene expression inhibitor is an adeno-associated virus AAV recombinant vector for targeted inhibition of GABRD gene expression, the adeno-associated virus AAV recombinant vector for targeted inhibition of GABRD gene expression comprises a gRNA sequence of a targeted GABRD gene, and the gRNA sequence of the targeted GABRD gene is shown as SEQ ID NO. 1; (ii) The GABRD gene expression inhibitor is WP1066; (iii) The GABRD gene expression inhibitor is IL-10R1 neutralizing antibody, the amino acid sequence of the heavy chain variable region of the IL-10R1 neutralizing antibody is shown as SEQ ID NO. 8, and the amino acid sequence of the light chain variable region of the IL-10R1 neutralizing antibody is shown as SEQ ID NO. 9.
  2. 2. The use according to claim 1, wherein the heavy chain variable region and/or the light chain variable region of the IL-10R1 neutralizing antibody is linked at the 5' end to a signal peptide.
  3. 3. The use according to claim 2, wherein the amino acid sequence of the signal peptide is shown in SEQ ID No. 10.
  4. 4. Use according to any one of claims 1 to 3, wherein the medicament is in the form of an injection or powder.
  5. 5. A medicament for treating hepatocellular carcinoma, characterized in that it comprises a GABRD gene expression inhibitor, the GABRD gene expression inhibitor being selected from any one of the following (i) to (iii): (i) The GABRD gene expression inhibitor is an adeno-associated virus AAV recombinant vector for targeted inhibition of GABRD gene expression, the adeno-associated virus AAV recombinant vector for targeted inhibition of GABRD gene expression comprises a gRNA sequence of a targeted GABRD gene, and the gRNA sequence of the targeted GABRD gene is shown as SEQ ID NO. 1; (ii) The GABRD gene expression inhibitor is WP1066; (iii) The GABRD gene expression inhibitor is IL-10R1 neutralizing antibody, the amino acid sequence of the heavy chain variable region of the IL-10R1 neutralizing antibody is shown as SEQ ID NO. 8, and the amino acid sequence of the light chain variable region of the IL-10R1 neutralizing antibody is shown as SEQ ID NO. 9.
  6. 6. The agent according to claim 5, wherein a signal peptide is linked to the 5' -end of the heavy chain variable region and/or the light chain variable region of the IL-10R1 neutralizing antibody.
  7. 7. The medicine according to claim 6, wherein the amino acid sequence of the signal peptide is shown in SEQ ID NO. 10.
  8. 8. A medicament according to any of claims 5 to 7, in the form of an injection or powder.

Description

Application of GABRD gene expression inhibitor in preparation of medicines for treating hepatocellular carcinoma Technical Field The invention belongs to the technical field of biological medicines, and particularly relates to application of GABRD gene expression inhibitor in preparation of medicines for treating hepatocellular carcinoma. Background Hepatocellular carcinoma (HCC) is one of the most challenging malignant tumors worldwide, and is characterized by high mortality, high recurrence rate, and intensive drug resistance, which are serious threatens to human life health. The current clinical treatment means aiming at the hepatocellular carcinoma mainly comprise surgical excision, liver transplantation, targeted treatment and the like, but the curative effects of the treatment modes are not ideal, so that the survival rate of patients in 5 years is only 18%. Therefore, the development of a novel and efficient treatment strategy by deeply mining key molecular targets for driving malignant progress of the hepatocellular carcinoma has become a core problem to be solved urgently in the current hepatocellular carcinoma research field. Although the regulatory role of neurotransmitter receptor family in tumor progression has been preliminarily confirmed, and the pro-cancerous role of GABRD in various tumors has been reported, no hepatocellular carcinoma treatment regimen or drug based on GABRD target is currently available, since its function and mechanism of action in hepatocellular carcinoma are not yet clear. Meanwhile, the problems of limited curative effect, high recurrence rate, strong drug resistance and the like of the existing hepatocellular carcinoma treatment means are not solved effectively, and a new treatment strategy based on a new target point is required to be developed clinically so as to fill the blank of the current hepatocellular carcinoma treatment field and improve the prognosis of patients. From the research trend of tumor treatment, the treatment strategy of targeting specific molecular targets has become an important direction of malignant tumor treatment due to the advantages of strong pertinence, small side effect and the like. However, in the field of hepatocellular carcinoma, effective targeted therapeutic targets for clinical selection are limited because the excavation of key driving targets is not deep enough. Combining GABRD with the pro-cancerous nature of other tumors, it is expected to become a potential novel target for hepatocellular carcinoma therapy, however, the related research on hepatocellular carcinoma around the target is still blank, and corresponding therapeutic drugs and strategies are lacking, so that no new therapeutic options can be provided for hepatocellular carcinoma patients, which further highlights the urgency and necessity of developing a hepatocellular carcinoma therapy scheme based on GABRD target. Disclosure of Invention Based on the above, the invention aims to provide an application of GABRD gene expression inhibitor in preparing medicines for treating hepatocellular carcinoma. In order to achieve the above purpose, the present invention may adopt the following technical scheme: in one aspect, the present invention provides an application of GABRD gene expression inhibitor in preparing a medicament for treating hepatocellular carcinoma, wherein GABRD gene expression inhibitor is selected from any one of the following (i) to (iii): (i) The GABRD gene expression inhibitor is an adeno-associated virus AAV recombinant vector for targeted inhibition of GABRD gene expression, the adeno-associated virus AAV recombinant vector for targeted inhibition of GABRD gene expression comprises a gRNA sequence of a targeted GABRD gene, and the gRNA sequence of the targeted GABRD gene is shown as SEQ ID NO. 1; (ii) The GABRD gene expression inhibitor is WP1066; (iii) The GABRD gene expression inhibitor is IL-10R1 neutralizing antibody, the amino acid sequence of the heavy chain variable region of the IL-10R1 neutralizing antibody is shown as SEQ ID NO. 8, and the amino acid sequence of the light chain variable region of the IL-10R1 neutralizing antibody is shown as SEQ ID NO. 9. Preferably, in the above application, the heavy chain variable region and/or the light chain variable region of the IL-10R1 neutralizing antibody is linked at the 5' end to a signal peptide. More preferably, in the above application, the amino acid sequence of the signal peptide is shown in SEQ ID NO. 10. Preferably, in the above application, the dosage form of the medicament is injection or powder. In another aspect, the present invention provides a medicament for treating hepatocellular carcinoma comprising GABRD gene expression inhibitor, GABRD gene expression inhibitor selected from any one of the following (i) to (iii): (i) The GABRD gene expression inhibitor is an adeno-associated virus AAV recombinant vector for targeted inhibition of GABRD gene expression, the adeno-associated vir