Small interfering ribonucleic acid (siRNA) lipid nanometer vesicles with targeted hepatic stellate cells, and application of siRNA lipid nanometer vesicles

A technology of hepatic stellate cells and nanovesicles, applied in liposome delivery, medical preparations containing active ingredients, genetic material components, etc., can solve poor endocytosis effect, poor cell targeting ability, easy to be Ribozyme degradation and other issues to achieve the effect of avoiding phagocytosis, improving encapsulation rate, and solving delivery obstacles

Inactive Publication Date: 2016-06-22
EAST CHINA NORMAL UNIV
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Problems solved by technology

[0002] Gene therapy is an effective treatment method, which can be used to treat a variety of diseases that seriously threaten human health. However, naked gene therapy drugs have disadvantages such as easy degradation by ribozymes, poor endocytosis and poor cell targeting ability.

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  • Small interfering ribonucleic acid (siRNA) lipid nanometer vesicles with targeted hepatic stellate cells, and application of siRNA lipid nanometer vesicles
  • Small interfering ribonucleic acid (siRNA) lipid nanometer vesicles with targeted hepatic stellate cells, and application of siRNA lipid nanometer vesicles
  • Small interfering ribonucleic acid (siRNA) lipid nanometer vesicles with targeted hepatic stellate cells, and application of siRNA lipid nanometer vesicles

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Embodiment Construction

[0028] The invention relates to the preparation and application of targeted nanovesicles of hepatic stellate cells. In the specific implementation process, it involves the screening of siRNA, the construction of micro-preparation devices, the preparation of nano-lipid vesicles, the establishment of animal models with high gene expression and the verification of results.

[0029] 1. Screening of siRNA

[0030] Heat shock protein 47 (hsp47, the homologous gene in mice is GP46) is a specific molecular chaperone of collagen, which can promote the secretion of collagen and plays an important role in liver fibrosis. Studies have shown that liver fibrosis in both humans and animals can be reversed by inhibiting collagen synthesis. Therefore, the present invention designs three siRNA sequences that can simultaneously silence hsp47 or GP46 as therapeutic components to construct an siRNA lipid nanovesicle delivery system for fibrosis treatment. The three siRNA sequences are:

[0031]...

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Abstract

The invention relates to the technical field of gene therapy drugs, and in particular discloses small interfering ribonucleic acid (siRNA) lipid nanometer vesicles with targeted hepatic stellate cells, and the application of the siRNA lipid nanometer vesicles. The nanometer vesicles respectively comprise a treatment component and a delivery component, wherein the treatment component is siRNA having a targeted gene inhibition effect, and the delivery component is a lipid carrier. The nanometer vesicles formed by encapsulating the treatment component by the delivery component are prepared by an ethanol dilution method; a gene delivery system existing in a form of nanometer vesicles is capable of effectively overcoming the obstacles preventing the delivery of the gene therapy drugs in the body.

Description

technical field [0001] The invention relates to the technical field of gene therapy and nano-targeted delivery, and is an effective method for realizing liver-targeted delivery of gene medicine and exerting a therapeutic effect. Background technique [0002] Gene therapy is an effective treatment method, which can be used to treat a variety of diseases that seriously threaten human health. However, naked gene therapy drugs have disadvantages such as easy degradation by ribozymes, poor endocytosis and poor cell targeting ability. The key to the success of gene therapy is to choose an appropriate gene delivery system to make the target gene target, controllable and effective expression. [0003] At present, the delivery systems of exogenous genes mainly include viral delivery systems and non-viral delivery systems, among which non-viral delivery systems are highly expected due to their safety, low toxicity, low immune response, targeting and easy assembly. The essence of the...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K48/00A61K31/7088A61K9/127A61P1/16
CPCA61K9/1271A61K31/7088A61K48/0033A61K48/0066
Inventor 王依婷皮玉芳刘雪莹贾宗翔祁伟王镜朱建中闫志强俞磊
Owner EAST CHINA NORMAL UNIV
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