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Cationic polymer gene vector having low cytotoxicity and high transfection efficiency, preparation method and use thereof

A cationic polymer and gene carrier technology, applied in the field of biomedicine, can solve the problems of high gene transfection efficiency, cytotoxicity, and low transfection efficiency, and achieve the goal of improving gene transfection efficiency, high transfection efficiency, and reducing cytotoxicity Effect

Inactive Publication Date: 2010-08-04
THE FIRST AFFILIATED HOSPITAL OF SUN YAT SEN UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Studies have proved that when the molecular weight of PEI is 25k, it has higher gene transfection efficiency and higher cytotoxicity; when the molecular weight of PEI is less than 2k, it has basically no cytotoxicity and can be excreted through metabolism, but its transfection low efficiency

Method used

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  • Cationic polymer gene vector having low cytotoxicity and high transfection efficiency, preparation method and use thereof
  • Cationic polymer gene vector having low cytotoxicity and high transfection efficiency, preparation method and use thereof
  • Cationic polymer gene vector having low cytotoxicity and high transfection efficiency, preparation method and use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] 1.1 Synthesis of polyethyleneimine-polyaldehyde sodium alginate graft copolymer MASA-PEI

[0043] According to the applicant's patent method (see ZL 200610036842.8) to synthesize polyaldehyde sodium alginate MASA. Take polyaldehyde sodium alginate 0.5g (containing aldehyde group 1.46×10 -3 mol, the degree of oxidation is 0.29, M η =33K), dissolved in 10ml of water to obtain solution 1. 5.27g polyethyleneimine PEI 1.8k (2.92×10 -3 mol, n 醛基 / n PEI 1.8k =1 / 2, n represents the amount of substance, and the unit is mole) is dissolved in 30ml water, adjusts pH to 8 with 3M hydrochloric acid, adjusts solution total volume to 55ml with distilled water, and this is solution 2. The solution 1 was slowly dropped into the solution 2 under stirring, and the drop was completed within 1 hour. After dropping, the reaction was stirred at room temperature for 24 h. The reaction product was dialyzed in distilled water for 72h, the insoluble matter was filtered off, and MASA-PEI wa...

Embodiment 2

[0047] 1.1 Synthesis of polyethyleneimine-polyaldehyde sodium alginate graft copolymer MASA-PEI

[0048] According to the applicant's patent method (see ZL 200610036842.8) to synthesize polyaldehyde sodium alginate MASA. Take polyaldehyde sodium alginate 0.5g (containing aldehyde group 1.46×10 -3 mol, the degree of oxidation is 0.29, M η =33K), dissolved in 10ml of water to obtain solution 1. 1.24g PEI 423 (2.92×10 -3 mol, n 醛基 / n PEI0423k =1 / 2, n represents the amount of substance, and the unit is mole) is dissolved in 30ml water, adjusts pH to 8 with the sulfuric acid of 3M, adjusts solution total volume to 55ml with distilled water, and this is solution 2. The solution 1 was slowly dropped into the solution 2 under stirring, and the drop was completed within 1 hour. After dropping, the reaction was stirred at room temperature for 36 h. The reaction product was dialyzed in distilled water for 72h, the insoluble matter was filtered off, and MASA-PEI was obtained after...

Embodiment 3

[0052] 1.1 Synthesis of polyethyleneimine-polyaldehyde sodium alginate graft copolymer MASA-PEI

[0053] According to the applicant's patent method (see ZL200610036842.8), polyaldehyde sodium alginate MASA was synthesized. Take polyaldehyde sodium alginate 0.5g (containing aldehyde group 1.92×10 -3 mol, the degree of oxidation is 0.38, M η =24K), dissolved in 10ml of water to obtain solution 1. 6.91g PEI 1.8k (3.84×10 -3 mol, n 醛基 / n PEI1.8k =1 / 2, n represents the amount of substance, and the unit is mole) is dissolved in 30ml water, adjusts pH to 7 with 2M hydrochloric acid, adjusts solution total volume to 55ml with distilled water, and this is solution 2. The solution 1 was slowly dropped into the solution 2 under stirring, and the drop was completed within 1 hour. After dropping, the reaction was stirred at room temperature for 36 h. The reaction product was dialyzed in distilled water for 60 h, the insoluble matter was filtered off, and MASA-PEI was obtained after...

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Abstract

The invention discloses a cationic polymer gene vector having low cytotoxicity and high transfection efficiency, which takes multi aldehydesodium alginate (MASA) as a framework and Poly(ethylene imine) PEI as lateral chain, wherein the molecule amount of the PEI is smaller than 2K. The invention further discloses a preparation method and use of the cationic polymer gene vector. The graft copolymer has low cost, low cytotoxicity, low biodegradability, and high transfection efficiency not affected by serum, and is a cationic polymer gene vector having wide application range and good prospect.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and specifically relates to a biodegradable cationic polymer gene carrier with sodium alginate as a skeleton and polyethyleneimine as a side chain, and a preparation method and application thereof. Background technique [0002] Gene therapy is a new method of transferring therapeutically significant genetic material to human cells to express the required polypeptides and proteins, so as to achieve the purpose of curing diseases. How to use vectors to introduce exogenous genes into target cells accurately and effectively is the key technology for the success of gene therapy. Gene vectors include viral and non-viral vectors. Retroviruses, adenoviruses, adeno-associated viruses and other viral vectors are used in 80% of current clinical experimental studies. The advantage of viral vectors is high transfection efficiency, but the disadvantages are potential safety hazards such as immunogenicity...

Claims

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Application Information

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IPC IPC(8): A61K47/36A61K47/32A61K48/00
Inventor 王琴梅何文郭振寰滕伟
Owner THE FIRST AFFILIATED HOSPITAL OF SUN YAT SEN UNIV
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