Gene-vector composition of targeted microglia as well as preparation method and application of gene-vector composition

A technology of microglia and gene carrier, applied in the field of biomedicine, can solve the problem of not causing chemotactic movement, achieve the effect of inhibiting occurrence or deterioration, good development and application prospects, and inhibiting nervous system diseases

Inactive Publication Date: 2012-07-04
THE SECOND AFFILIATED HOSPITAL ARMY MEDICAL UNIV
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Problems solved by technology

The study found that the seductive ligand polypeptide H9 derived from the N-terminus of the US28 receptor can block the chemotaxis formed by the human CX3CR1 receptor binding to physiological chemokines, but it does not cause chemotactic movement and does not affect intracellu

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  • Gene-vector composition of targeted microglia as well as preparation method and application of gene-vector composition
  • Gene-vector composition of targeted microglia as well as preparation method and application of gene-vector composition
  • Gene-vector composition of targeted microglia as well as preparation method and application of gene-vector composition

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Embodiment Construction

[0029] In order to make the object, technical solution and advantages of the present invention clearer, preferred embodiments of the present invention will be described in detail below with reference to the accompanying drawings. The experimental method not indicating the specific conditions in the preferred embodiment is usually according to the conventional conditions, such as described in the Molecular Cloning Experiment Guide (Third Edition, J. Sambrook et al., translated by Huang Peitang et al., Science Press, 2002) conditions, or as recommended by the manufacturer.

[0030] 1. Preparation of gene-carrier complex targeting microglia

[0031] 1. Synthesis of H9 polypeptide

[0032]The amino acid sequence of the H9 polypeptide is VLNAHCALH (SEQ ID No.1). Its synthesis was carried out on an ABI 431A solid-phase peptide synthesizer using a standard fluorenylmethoxycarbonyl (Fmoc) protocol. 0.125 mmol of p-hydroxymethylphenoxymethyl polystyrene (HMP) resin was initially sel...

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Abstract

The invention discloses a gene-vector composition of targeted microglia. The gene-vector composition is formed by combining a CX3CR1shRNA (Ribose Nucleic Acid) interference vector and a gene vector through an electrostatic interaction, wherein the gene vector is conjugate of H9 polypeptide and chitosan; the composition can be successfully targeted to a specific CX3CR1 acceptor molecule on the surface of the microglia under the guiding action of the H9 polypeptide; and while the H9 polypeptide exerts the antagonism for a CX3CR1 acceptor, the CX3CR1shRNA interference vector can be efficiently transfected into the microglia to intervene the expression of the CX3CR, inhibit the activation of the microgli and further inhibit the generation or deterioration of microglia-medicated nervous system diseases. The invention also discloses a preparation method of the gene-vector composition. The preparation method is simple and convenient to operate; the obtained gene-vector composition is nanoparticles with uniformity in size so as to bring convenience to uptake of cells; the gene-vector composition disclosed by the invention can be used for preparing a microglia activator inhibitor and has favorable development and application prospect in the field of treatment on the microglia-medicated nervous system diseases.

Description

technical field [0001] The invention belongs to the field of biomedicine, relates to a gene-carrier complex with cell targeting, and also relates to a preparation method and application of the gene-carrier complex. Background technique [0002] As the main effector cells involved in the immune response in the central nervous system, microglia play an important role in the inflammatory response. When foreign pathogens invade or cells die, microglia are quickly activated and eliminated, and at the same time release inflammatory factors to mediate the inflammatory response. However, studies have shown that overactivated microglia may accelerate the process of some central nervous system diseases, and the cytotoxic factors released by them will also cause further damage to nerve cells. For example, in Alzheimer's disease, active microglia are found in the same areas of the cortex as neuritic plaques; High numbers of activated microglia; in multiple sclerosis, the degree of axo...

Claims

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Application Information

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IPC IPC(8): C12N15/85C12N15/66A61K48/00A61P25/00
Inventor 刘勇杨曌罗海鸥
Owner THE SECOND AFFILIATED HOSPITAL ARMY MEDICAL UNIV
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