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Gene delivery carrier and preparation and application thereof

A technology of gene delivery and carrier, applied in the field of gene delivery carrier and its preparation and application, can solve the problems of complex preparation, tumorigenicity, low DNA loading capacity, etc., and achieve uniform distribution, good stability and good transfection effect. Effect

Inactive Publication Date: 2017-12-08
SHANGHAI JIAO TONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although viral vectors have greatly promoted the development of the field of gene therapy, there are still great limitations in gene therapy using viruses as vectors, including potential tumorigenicity, immunogenicity, and extensive tissue tropism, and this type of vector has a negative effect on gene therapy. DNA loading capacity is low and preparation is complex

Method used

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  • Gene delivery carrier and preparation and application thereof
  • Gene delivery carrier and preparation and application thereof
  • Gene delivery carrier and preparation and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0063] 1.1 Selection of cationic lipids, the synthesis and acquisition of the following cationic lipids are all existing technologies.

[0064] (1) The structural formula of ionizable cationic lipid DLin-MC2-MPZ (hereinafter referred to as MPZ) is shown in formula (1), specifically:

[0065]

[0066] (2) The structural formula of ionizable cationic lipid DLin-MC3-DMA is shown in formula (2), specifically:

[0067]

[0068] (3) The structural formula of ionizable cationic lipid DLin-KC2-DMA is shown in formula (3), specifically:

[0069]

[0070] (4) The structural formula of cationic lipid DOTAP is shown in formula (4), specifically:

[0071]

[0072] (5) The structural formula of cationic lipid DOTMA is shown in formula (5), specifically:

[0073]

[0074] (6) The structural formula of cationic lipid MVL5 is shown in formula (6), specifically:

[0075]

[0076] (7) The structural formula of cationic lipid DDAB is shown in formula (7), specifically:

[0077]

[0078] (8) The structural for...

Embodiment 2

[0127] 2.1 Use neutral lipid DSPC, auxiliary lipid cholesterol, ionizable cationic lipid (1) DLin-MC2-MPZ, cationic lipid DOTAP as carrier materials; and use luciferase expression plasmid pGL3 as a drug model to construct Gene delivery vector.

[0128] Specifically, the range of the molar ratio between DSPC:CHOL: (DLin-MC2-MPZ+DOTAP) is: (5~40): (30~50): (30~55) (DLin-MC2-MPZ accounts for the total cations The molar ratio of lipids is 5% to 90%); the N / P ratio between all cationic lipids = 3:1, refer to the method of 1.2 to construct the pDNA delivery vector lipoplex, its particle size and Zeta potential are shown in Table 3. Shown:

[0129] table 3

[0130]

[0131] Through the human non-small cell lung cancer cell line H1299, the transfection effect was investigated. The positive control group DOTAP was set, and the transfection efficiency of the positive control group was defaulted to 100%. The experimental group data / positive control data is the experimental group transfection ...

Embodiment 3

[0140] 3.1 Selecting cationic lipid gene delivery vector constructed in Example 2 embodiment, having added amphiphilic PEG-lipids, while forming lipid -DNA nanocomposite particles, PEG-lipids in the hydrophobic end (i.e., long carbon chain hydrophobic ends ) embedded in a lipid layer, PEG hydrophilic ends remaining in the aqueous phase, forming a hydration layer on the surface of the particle, positively charged surface of the particle shield the cationic lipid, reducing the side effects of the particles, the particles in the aqueous phase facilitates In order to construct a gene delivery vector with small particle size, good stability, high reproducibility and high drug loading capacity. The H1299 cell line was subjected to in vitro transfection experiments.

[0141] PEG-lipids selected, PEG-lipids are the following prior art can be obtained.

[0142] (1) The structural formula of PEG-DSPE is shown in formula (11), specifically:

[0143] R=C 17 H 35 , N=5-125, the molecular weigh...

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Abstract

The invention belongs to the field of drug preparation research and development and particularly relates to a gene delivery carrier and preparation and application thereof. The gene delivery carrier comprises a neutral lipid, an auxiliary lipid, a positive ion lipid and gene drugs. According to the gene delivery carrier constructed by the invention, under the condition of physiological pH, the particle diameter is 50-500 nm, distribution is even, the surface potential is between negative 10 mv and positive 10 mv, and the stability is good. What is more, the gene delivery carrier has a very good transfection effect on the gene drugs, especially the DNA drugs, comprising pDNA, needing to be delivered into cell nucleuses to come into play.

Description

Technical field [0001] The invention belongs to the field of drug preparation research and development, and specifically relates to a gene delivery carrier and its preparation and application. Background technique [0002] Gene therapy refers to the introduction of therapeutically significant foreign gene drugs into target cells to correct abnormal genes or compensate for missing genes, so that the corresponding protein can be expressed normally, so as to achieve the purpose of treatment. Gene therapy can be used to effectively treat congenital and acquired diseases, and has been used in cancer, acquired immunodeficiency syndrome (AIDS), heart disease, infectious diseases, vesicular fibrosis, X-linked severe immunodeficiency (X-linked SCID) and other diseases have shown its great potential. In theory only, the concept of gene therapy is not difficult to understand, that is, abnormal gene replacement and missing gene compensation; in fact, gene therapy has many problems to be sol...

Claims

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Application Information

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IPC IPC(8): A61K48/00A61K47/22A61K47/16A61K47/18
CPCA61K48/0033A61K47/16A61K47/186A61K47/22A61K48/0041
Inventor 徐宇虹张琰曹婧魏晓慧许风伟魏爽
Owner SHANGHAI JIAO TONG UNIV