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Target polypeptide modified positive ion copolymer gene vector and preparation method and application

A technology of cationic copolymers and targeting peptides, which is applied in the field of biomedicine and can solve problems such as unfavorable cell uptake and increased particle size of gene complexes

Inactive Publication Date: 2019-05-10
QINGHAI UNIV FOR NATITIES +1
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the particle size of the gene complex will increase significantly after the existing TAT-NLS combination peptide modification, which is not conducive to cell uptake

Method used

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  • Target polypeptide modified positive ion copolymer gene vector and preparation method and application
  • Target polypeptide modified positive ion copolymer gene vector and preparation method and application
  • Target polypeptide modified positive ion copolymer gene vector and preparation method and application

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Embodiment 1

[0036] A cationic copolymer gene carrier targeting polypeptide modification, the preparation method of which comprises the following steps:

[0037] 1. Preparation of PCLMD-g-PEI copolymer (g is the abbreviation of graft, representing graft copolymerization)

[0038] (1) Preparation of poly(caprolactone-co-3(S)-methyl-morpholine-2,5-dione) (PCLMD-OH) copolymer

[0039] With 1,8-octanediol 0.07g (0.47mmol) as the initiator, Sn(Oct) 2 (0.4ml, 0.25mol / l) toluene solution is used as a catalyst to initiate caprolactone (CL) 4.5g (39.4mmol) and 3-methyl-morpholine-2,5-dione (MMD) 0.5g (3.9mmol) ) ring-opening polymerization to prepare PCLMD-OH copolymer, the specific process is: mix 1,8-octanediol, caprolactone and 3-methyl-morpholine-2,5-dione, then add Sn(Oct ) 2 Toluene solution, sealed, vacuumed, nitrogen, and then put in an oil bath, reacted at 120-140 ° C for 22-26h, the initial product obtained was dissolved in chloroform, precipitated in ice-cold n-hexane, and dissolved a...

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Abstract

The invention provides a target polypeptide modified positive ion copolymer gene vector, a preparation method and application. The preparation method comprises the steps of preparing a PCLMD-g-PEI copolymer; grafting the PCLMD-g-PEI to the target polypeptide to prepare the gene vector. The vector and a pDNA solution are mixed, and a gene composition is prepared. The obtained gene vector has low cell toxicity, when the target polypeptide is a step-by-step target polypeptide REDV-G-TAT-G-NLS, the vector has the ECs adhesion function, the cell membrane target function and the cell nucleus targetfunction, on the basis of the specific proton effect of the PEI, the gene composition has the endosome / lysosome escape function, and therefore the gene transfer effect is improved, the transfection efficiency is improved, and cell migration and proliferation are promoted.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to a targeted polypeptide modified cationic copolymer gene carrier and its preparation method and application. Background technique [0002] Gene therapy has emerged as one of the most promising therapeutic approaches for the treatment of various diseases, especially for cardiovascular diseases. However, it is still a daunting task to develop gene vectors with high biocompatibility and high efficiency for gene delivery to overcome multiple obstacles. A nanoparticle gene delivery system with a core-shell structure, the hydrophobic core maintains the stability of the structure, and the hydrophilic shell reduces the interaction between the carrier and plasma proteins, thereby preventing the aggregation of the carrier. Additionally targeting genetic material to a specific site of action has many advantages over untargeted delivery. Carriers with specific targeting liga...

Claims

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Application Information

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IPC IPC(8): C12N15/87C08G81/00C08J3/03C08L87/00A61K48/00A61P35/00
Inventor 朵兴红冯亚凯白凌闯
Owner QINGHAI UNIV FOR NATITIES
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