Functional oligomer used for non-viral gene vector material and application thereof

Abstract

The invention provides a functional oligomer used for a non-viral gene vector material. The functional oligomer is prepared by free radical polymerization of MA-His-OMe and MAEL through taking water-soluble thio ester as a molecular weight regulating agent. In the preparation method, MA-His-OMe and MAEL are used as monomers, AIBN (2,2-azobisisbutyronitrile) or ACVA (4,4'-azobix(4-cyano valeric acid)) is used as an initiator, and CPADB (4-cyanopentanoic acid dithiobenzoate) is used as a chain transfer agent. According to the invention, the functional oligomer is mixed with a polycation material to prepare a DNA (deoxyribonucleic acid) or RNA (ribonucleic acid) composite which is used as the non-viral gene vector material and a cell transfection experiment is carried out. The functional oligomer has the advantages that the functional oligomer has a good protection effect on plasma DNA and can be used for improving the binding action of a complex particle and a cell membrane surface and improving the escape efficiency of the plasma DNA from lysosme / endosome in a cell, thus the transfection efficiency of the complex particle on cells such as HeLa is greatly improved, and the toxicity of the functional oligomer is greatly reduced, therefore the functional oligomer is expected to reach a clinical application level.

Description

technical field [0001] The invention belongs to the field of gene therapy and new materials, in particular to a functional oligomer used for non-viral gene carrier materials and its application. Background technique [0002] Gene therapy is a technology that uses molecular biology methods to introduce a target gene into a patient to express the target gene product, so that the disease can be treated. Gene carrier is one of the core technologies in the field of gene therapy. Gene vectors are usually divided into viral vectors and non-viral vectors. In most cases, viral vectors have high transfection efficiency, but there are problems such as potential toxicity and immunogenicity, which limit their application in clinical treatment; although non-viral vectors The above problems can be overcome, but unfavorable biodistribution and inefficient intracellular operation lead to low transfection rate of active genes. Therefore, improving the transfection rate of non-viral gene vect...

AI Technical Summary

Problems solved by technology

The main problem of these polymer materials as gene carrier materials is that the complex particles formed with DNA or RNA are prone to specific interactions and adsorption of some proteins in physiological environments, thereby affecting their endocytosis and consequently The speed of escape from endosomes or lysosomes in turn affects transfection efficiency

The way to overcome this problem is mainly through chemical modification, such as introducing PEG chain segments into its structure through chemical modification methods, but this method often consumes the amino groups in the polycation structure at the same time, reducing its ability to compress DNA

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