Assembly method for core-shell structural gene support system and uses thereof

Abstract

The invention discloses a method for assembling a gene vector system with a nuclear shell structure. The method has the following steps: complete ring-opening is carried out on small molecular weight polymine (PEI) to gather L-aspartame (PSI), alpha, beta-polyL-aspartame-g-polymine (AE) are obtained after purification, the AE is taken as a carrier to be assembled into a nano gene vector system with the nuclear shell structure with DNA; the invention is characterized in that the synthetic method of brush-shaped polycation is simple and the cost is low; as the used raw material is free from toxicum, the gene vector of the obtained brush-shaped polycation has low toxicity; the brush-shaped polycation and DNA can form nano-particle with the nuclear shell structure by charge interaction; the nano-particle has high gene transfection efficiency; base on a hydrophilic shell layer, the nano-particle can reduce absorption on protein, so that the nano-gene vector system with the nuclear shell structure has fine gene transfection efficiency with the existence of blood plasma and is expected to be used in treatment of in vivo genes.

Description

technical field [0001] The invention relates to the technical field of nano-biomedicine, in particular to an assembly method and application of a core-shell structure gene carrier system. Background technique [0002] Because gene therapy can treat or prevent congenital genetic diseases or acquired diseases from the gene level, it has created a revolutionary new way to treat diseases in the field of biomedicine. Although there have been thousands of clinical trials in the past 20 years, the U.S. Food and Drug Safety Administration has not yet approved any gene therapy program due to its unsatisfactory effect. Therefore, it is necessary to improve the transfection efficiency and clinical safety of therapeutic genes remains a challenging subject. Viral vectors are used in most clinical trials based on the advantages of high transfection efficiency. However, their defects such as high immunogenicity, carcinogenicity, non-guidance, inability to use multiple medications, and hig...

AI Technical Summary

Problems solved by technology

Although there have been thousands of clinical trials in the past 20 years, the U.S. Food and Drug Safety Administration has not yet approved any gene therapy program due to its unsatisfactory effect. Therefore, it is necessary to improve the transfection efficiency and clinical safety of therapeutic genes Still a challenging subject

Viral vectors are used in most clinical trials based on the advantages of high transfection efficiency. However, their defects such as high immunogenicity, carcinogenicity, non-guidance, inability to use multiple medications, and high preparation costs make them low in toxicity, low in immunogenicity, and clinically acceptable. Non-viral genotype vectors with higher safety and easy preparation have received more attention

[0003] Polycations based on polyethyleneimine (PEI) have been widely studied as gene carriers because of their good gene transfection efficiency and easy structure modification. low transfection efficiency

Kissel et al. modified PEI with polyethylene glycol (Bioconjugate Chem.2006, 17, 1209-1218) in order to reduce the adsorption of hemoglobin, but it reduced the endocytic ability of cells to polymer / gene composite nanoparticles and the transfection efficiency not ideal

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