Three-function peptide-modified gene carrier as well as preparation method and application thereof

Abstract

The invention relates to a three-function peptide-modified gene carrier as well as a preparation method and application thereof, particularly provides a polypeptide with the functions of tumour targeting, membrane penetrating boosting and core positioning, a gene carrier formed by coupling the polypeptide and amphiphilic chitosan-modified polyethyleneimine, a preparation method of the gene carrier, a compound prepared from the gene carrier and DNA, and the application of the polypeptide with the three functions and the gene carrier in the preparation of a medicine for gene treatment. The three-function peptide-modified gene carrier is high in internal transfection efficiency, low in cytotoxicity, strong in targeting performance, and has wide clinical application prospect.

Description

technical field [0001] The invention relates to the technical fields of genetic engineering and molecular biology, in particular to a gene carrier modified by a trifunctional peptide and its preparation method and application. Background technique [0002] Gene therapy is a new treatment method based on genetic engineering technology and molecular genetics in recent years. Because the biological basis of tumor occurrence and development is gene mutation, gene therapy has become the most hopeful and most researched way to overcome tumors. active field. [0003] There are three important links in gene therapy, namely the target gene, transgenic carrier and target cells. Gene transfer system is the core technology of gene therapy. The biggest problem at this stage is that the ideal gene carrier has not yet been found. Currently applied vectors include two categories: viral vectors and non-viral vectors. Viral vectors have high transfection efficiency but have problems such ...

AI Technical Summary

Problems solved by technology

However, there are two outstanding problems in the use of PEI as a gene carrier

First, there is a contradiction between transfection efficiency and cytotoxicity: although small-molecule PEI has low cytotoxicity, it is prone to dissociation with DNA at physiological ion concentrations, resulting in poor transfection effect; although PEI with a molecular weight above 20kDa has a relatively ideal Transfection efficiency, but due to the positive charge on the surface of PEI and non-degradability in vivo, high molecular weight PEI exhibits strong cytotoxicity

Second, PEI has poor targeting: it uses its own positive charge to combine with negatively charged receptors on the cell surface through electrostatic interaction, so the specificity of cell selection is poor, and it has become a non-viral vector to solve the problem of targeting The most concerned issues in

[0007] However, although the above two non-viral gene carrier systems have a series of advantages such as enhanced humoral stability, significantly reduced cytotoxicity, improved in vitro transfection efficiency and tumor targeting ability, their in vivo transfection efficiency is significantly lower than in vitro. This is also a common problem in the current research on non-viral gene vectors

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