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Glucan-agmatine polycation transgenic vector, and preparation method and application thereof

A technology of transgenic carrier and agmatine, which is applied in the direction of gene therapy, the use of carriers to introduce foreign genetic material, and pharmaceutical formulations, can solve problems affecting biological performance and glucan main chain damage, and achieve improved efficiency and performance Improved transfection efficiency and good biocompatibility

Inactive Publication Date: 2012-02-01
TIANJIN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The main chain of dextran obtained by the above method is destroyed, which will affect its biological properties

Method used

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  • Glucan-agmatine polycation transgenic vector, and preparation method and application thereof
  • Glucan-agmatine polycation transgenic vector, and preparation method and application thereof
  • Glucan-agmatine polycation transgenic vector, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] (1) Dissolve dextran (2g, 12.4mmol) in 20mL of water, adjust the pH to 13 with NaOH, stir in an ice-water bath, then dissolve p-toluenesulfonyl chloride (2.4g, 12.4mmol) in 20mL of acetonitrile , and dropwise added to the aqueous solution of dextran within half an hour, a white precipitate will appear immediately, then react at room temperature for 3 hours, filter the precipitate with suction, lyophilize after dialysis for 5 days, and obtain p-toluenesulfonyl Dextran;

[0042] (2) Dissolve lauric acid (1.8mmol) and carbonyldiimidazole (CDI) (1.8mmol) in 3mL dimethyl sulfoxide (DMSO), respectively, and add the solution of CDI to the lauric acid solution, and react at 80°C for 3 Hours, p-tosylated dextran (6mmol) was dissolved in 5ml DMSO, and added to the solution of lauric acid and CDI, reacted at 80°C for 6 hours, then precipitated the product with 100mL ethanol, and washed several times, Suction filter the precipitate, dialyze for 5 days and freeze-dry to obtain laur...

Embodiment 2

[0046] (1) Dissolve dextran (2g, 12.4mmol) in 20mL of water, adjust the pH to 13 with NaOH, stir in an ice-water bath, then dissolve p-toluenesulfonyl chloride (4.8g, 24.8mmol) in 20mL of acetonitrile , and dropwise added to the aqueous solution of dextran within half an hour, a white precipitate will appear immediately, then react at room temperature for 3 hours, filter the precipitate with suction, lyophilize after dialysis for 5 days, and obtain p-toluenesulfonyl Dextran;

[0047] (2) Dissolve lauric acid (1.8mmol) and carbonyldiimidazole (CDI) (1.8mmol) in 3mL dimethyl sulfoxide (DMSO), respectively, and add the solution of CDI to the lauric acid solution, and react at 80°C for 3 Hours, p-tosylated dextran (6mmol) was dissolved in 5ml DMSO, and added to the solution of lauric acid and CDI, reacted at 80°C for 6 hours, then precipitated the product with 100mL ethanol, and washed several times, Suction filter the precipitate, dialyze for 5 days and freeze-dry to obtain laur...

Embodiment 3

[0051] (1) Dissolve dextran (2g, 12.4mmol) in 20mL of water, adjust the pH to 13 with NaOH, stir in an ice-water bath, then dissolve p-toluenesulfonyl chloride (7.2g, 37.2mmol) in 20mL of acetonitrile , and dropwise added to the aqueous solution of dextran within half an hour, a white precipitate will appear immediately, then react at room temperature for 3 hours, filter the precipitate with suction, lyophilize after dialysis for 5 days, and obtain p-toluenesulfonyl Dextran;

[0052] (2) Dissolve lauric acid (1.8mmol) and carbonyldiimidazole (CDI) (1.8mmol) in 3mL dimethyl sulfoxide (DMSO), respectively, and add the solution of CDI to the lauric acid solution, and react at 80°C for 3 Hours, p-tosylated dextran (6mmol) was dissolved in 5ml DMSO, and added to the solution of lauric acid and CDI, reacted at 80°C for 6 hours, then precipitated the product with 100mL ethanol, and washed several times, Suction filter the precipitate, dialyze for 5 days and freeze-dry to obtain laur...

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Abstract

The invention discloses a cationic high-polymer transgenic vector having good biocompatibility, degradability and high stability, and a preparation method thereof. A glucan molecule is used as a main chain, and agmatine and fatty acid bonds are respectively connected to the main chain of the glucan molecule through hydroxyl groups on the main chain. Guanylation glucan and primary amine of agmatine are subjected to nucleophilic reaction through tosylation glucan, and such copolymerization mode can not destroy the main chain of the glucan and can change the primary amine into secondary amine. Meanwhile, in order to improve the transfection efficiency, the nontoxic fatty acid is introduced to enhance the hydrophobic property of the glucan-agmatine polycation.

Description

technical field [0001] The invention relates to a transgene carrier and a preparation method thereof, more specifically, to a modified glucan transgene carrier and a preparation method thereof. Background technique [0002] Gene therapy refers to the introduction of human normal genes or therapeutic genes into human target cells in a certain way to correct gene defects or exert therapeutic effects. The vectors used in gene therapy mainly include viral vectors (viral vector) and nonviral vectors (nonviral vector). Viral vectors have made some breakthroughs in gene therapy, but in the process of clinical application, their immunogenicity and potential carcinogenicity are still major hidden dangers that are difficult to overcome. As another way of gene delivery, non-viral vectors have been widely studied, including naked DNA, liposomes, and cationic polymers. [0003] In the past few decades, it has been confirmed that polycationic non-viral vectors can be effectively used fo...

Claims

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Application Information

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IPC IPC(8): C12N15/85A61K48/00A61K47/36C08B37/02
Inventor 刘文广杨建海王宏博
Owner TIANJIN UNIV
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