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Glucan-g-poly(L-lysine)-VAPG (valine-alanine-proline-glycine) nucleic acid carrier as well as preparation method and application thereof

A nucleic acid carrier, -VAPG technology, applied in the field of biomedical gene therapy, can solve the problems of cytotoxicity, reduced transfection efficiency, large particle size, etc., to achieve the effect of reducing biological toxicity, great application prospects, and improving transfection efficiency

Inactive Publication Date: 2017-11-28
TIANJIN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The Chinese patent with the publication number CN 105153439A discloses a polyethylene glycol-modified chitosan nucleic acid carrier containing endothelial cell-targeting peptide REDV, which can target endothelial cells, promote endothelial cell proliferation, and avoid being Endocytosis of other normal cells triggers an immune response, but the protonated chitosan surface has a large number of positive charges, the shielding effect of polyethylene glycol is limited, and the carrier system has non-specific contact with intracellular blood proteins, resulting in cytotoxicity. Moreover, the nucleic acid carrier has a large particle size and is easily cleared by the body, reducing the transfection efficiency.

Method used

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  • Glucan-g-poly(L-lysine)-VAPG (valine-alanine-proline-glycine) nucleic acid carrier as well as preparation method and application thereof
  • Glucan-g-poly(L-lysine)-VAPG (valine-alanine-proline-glycine) nucleic acid carrier as well as preparation method and application thereof
  • Glucan-g-poly(L-lysine)-VAPG (valine-alanine-proline-glycine) nucleic acid carrier as well as preparation method and application thereof

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Experimental program
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Embodiment 1

[0024]According to literature (Song, H.Q.; Dou, X.B.; Li, R.Q.; Yu, B.R.; Zhao, N.N.; Xu, F.J., General strategy to prepare different types of polysaccharide-graft-poly(aspartic acid) as degradable gene carriers. Acta Biomater 2015,12,156-65), in a three-neck flask equipped with a stirring bar, weigh 1.41g of dextran and 1.14g of N N'-dicarbonyl imidazole and dissolve them in 4mL of anhydrous dimethyl sulfoxide Then, N N'-dicarbonylimidazole solution was added dropwise to the dextran solution, and reacted for 24h under nitrogen atmosphere; after that, 3ml of ethylenediamine was dissolved in 6ml of anhydrous dimethyl sulfoxide, and Add dropwise to the above reaction solution, and continue to react for 48 h under nitrogen atmosphere. After the reaction, it was precipitated and washed with a large amount of acetone, dissolved in a small amount of water, placed in a fiber membrane dialysis bag with a molecular weight cut-off of 2 kDa, dialyzed with deionized water, and finally fre...

Embodiment 2

[0029] According to literature (Song, H.Q.; Dou, X.B.; Li, R.Q.; Yu, B.R.; Zhao, N.N.; Xu, F.J., General strategy to prepare different types of polysaccharide-graft-poly(aspartic acid) as degradable gene carriers. Acta Biomater 2015,12,156-65), in a three-neck flask equipped with a stirring bar, weigh 1.41g of dextran and 1.14g of N N'-dicarbonyl imidazole and dissolve them in 4mL of anhydrous dimethyl sulfoxide , then add N N'-dicarbonylimidazole solution dropwise to the dextran solution, and react for 24h under nitrogen atmosphere; after that, dissolve 3.5ml of ethylenediamine in 6ml of anhydrous dimethyl sulfoxide, and added dropwise to the above reaction solution, and continued to react for 48 h under nitrogen atmosphere. After the reaction, it was precipitated and washed with a large amount of acetone, dissolved in a small amount of water, placed in a fiber membrane dialysis bag with a molecular weight cut-off of 2 kDa, dialyzed with deionized water, and finally freeze-dr...

Embodiment 3

[0034] According to literature (Song, H.Q.; Dou, X.B.; Li, R.Q.; Yu, B.R.; Zhao, N.N.; Xu, F.J., General strategy to prepare different types of polysaccharide-graft-poly(aspartic acid) as degradable gene carriers. Acta Biomater 2015,12,156-65), in a three-neck flask equipped with a stirring bar, weigh 1.41g of dextran and 1.14g of N N'-dicarbonyl imidazole and dissolve them in 4mL of anhydrous dimethyl sulfoxide In, then N N'-dicarbonylimidazole solution was added dropwise to the dextran solution, and reacted for 24h under nitrogen atmosphere; after that, 4ml of ethylenediamine was dissolved in 6ml of anhydrous dimethyl sulfoxide, and Add dropwise to the above reaction solution, and continue to react for 48 h under nitrogen atmosphere. After the reaction, it was precipitated and washed with a large amount of acetone, dissolved in a small amount of water, placed in a fiber membrane dialysis bag with a molecular weight cut-off of 2 kDa, dialyzed with deionized water, and finally...

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Abstract

The invention provides a glucan-g-poly(L-lysine)-VAPG (valine-alanine-proline-glycine) nucleic acid carrier as well as a preparation method and an application thereof. The nucleic acid carrier comprises glucan, poly(L-lysine) and VAPG targeting polypeptide, wherein polylysine is prepared after epsilon-carbobenzoxy-L-lysine cyclic anhydride monomers is initiated by modified glucan for ring opening; then the VAPG targeting peptide and glucan-g-poly(L-lysine) are subjected to an addition reaction through sulfydryl-ethylene, and the targeting nucleic acid carrier is obtained. The glucan-g-poly(L-lysine)-VAPG nucleic acid carrier is simple and easy to obtain, and nanoparticles with uniform particle size and good water solubility can be obtained after the carrier is composited with a nucleic acid medicine. Additionally, the nucleic acid carrier can protect the nucleic acid medicine effectively, so that the nucleic acid medicine can enter smooth muscle cells, toxic and side effects of non-specific contact are reduced, the transfection efficiency is improved, the biocompatibility and the biodegradability are good, and the carrier has potential application prospects in the gene therapy field.

Description

technical field [0001] The invention relates to a dextran-g-poly(L-lysine)-VAPG nucleic acid carrier and a preparation method and application thereof, belonging to the field of biomedical gene therapy. Background technique [0002] In recent years, RNA interference has gradually developed into a new technology for the treatment of cancer and cardiovascular diseases. RNA interference induces the specific degradation or silencing of target gene mRNA in vivo through RNA effector molecules siRNA and miRNA, and then regulates the expression of the target gene. The effect is rapid and efficient, and it has high medical value in the treatment of diseases. However, naked nucleic acid drugs pDNA, miRNA and siRNA are easily degraded by nucleases, and their high molecular weight and surface negative charge make it difficult to enter cells through endocytosis to play a role. Therefore, safe and effective delivery vehicles have become gene therapy key. Cationic polymer is a widely used...

Claims

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Application Information

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IPC IPC(8): A61K47/64A61K48/00A61P9/00C08B37/02C08G69/10
CPCA61K48/0041C08B37/0006C08G69/10
Inventor 袁晓燕周培琼刘波赵蕴慧任丽霞
Owner TIANJIN UNIV