Non-viral vector, and preparation method and application thereof

Abstract

The invention discloses a non-viral vector, and a preparation method and application thereof. The non-viral vector is nanoparticles prepared by blending polyethyleneimine and a compound shown in a formula V. A vector of a medicament provided by the invention is the non-viral vector provided by the invention. The medicament comprises the non-viral vector provided by the invention and a therapeuticDNA wrapped in the non-viral vector. The target tumor of the medicament is highly expressed by a folate receptor FRalpha. The tumor which can be targeted by the medicament is a folate receptor FRalpha negatively-expressed tumor and heart. After being intravenously injected into a tumor-bearing mouse inoculated with the tumor of folate receptor positive cells, the non-viral vector provided by the invention can carry gene specificity to the tumor cells and continuously and effectively express target genes in the tumor cells.

Description

technical field [0001] The invention belongs to the field of macromolecular chemistry and biomedical engineering, and relates to a non-viral vector and its preparation method and application. Background technique [0002] Tumor is a genetic disease. The genetic background of tumor occurrence is the abnormality of oncogenes or tumor suppressor genes. Gene therapy is to transfer one or several normal genes to tumor cells or normal cells, and its expression products are conducive to directly or indirectly killing tumor cells. ; or protect normal cells from the severe damage of chemotherapy and radiotherapy, but the problems in the traditional gene transfer system are: (1) lack of targeting, and have high cytotoxicity and immunogenicity, such as carrying the p53 gene In the current adenovirus treatment of malignant tumors, the adenovirus can only be injected directly into the tumor. If injected intravenously, the virus particles will be cleared quickly, and there are very few t...

AI Technical Summary

Problems solved by technology

[0002] Tumor is a genetic disease. The genetic background of tumor occurrence is the abnormality of oncogenes or tumor suppressor genes. Gene therapy is to transfer one or several normal genes to tumor cells or normal cells, and its expression products are conducive to directly or indirectly killing tumor cells. ; or protect normal cells from the severe damage of chemotherapy and radiotherapy, but the problems in the traditional gene transfer system are: (1) lack of targeting, and have high cytotoxicity and immunogenicity, such as carrying the p53 gene In the current adenovirus treatment of malignant tumors, the adenovirus can only be injected directly into the tumor

If injected intravenously, the virus particles will be cleared quickly, and there are very few target genes that can really reach the tumor tissue, it is difficult to achieve the therapeutic effect, and the side effects are increased; (2) There are safety problems, and the current gene therapy program for genetic diseases Retroviral vectors are mostly used, and the position of insertion or integration into the chromosome is random, which has the potential risk of causing insertion mutation and malignant transformation of cells

(3) The efficiency of transfection and expression is low. Because the plasmid vector contains CpG sequence, it can be silenced by the body after entering the cell and cannot be continuously and efficiently expressed

[0007] Studies have shown that the covalent linkage between the exogenous gene expression cassette and the bacterial plasmid backbone can lead to the silencing of the exogenous gene, which is the main reason why the exogenous gene carried by the plasmid vector can only be expressed transiently in vivo, and it is also the Major Limiting Factors for Clinical Application

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