Liver-specific gene editing nano-drug as well as preparation method and application thereof

A gene editing and nanomedicine technology, applied in the field of biomedicine, can solve the problems of increasing the difficulty of treatment of chronic HBV infection, unable to completely remove HBV, unable to cure chronic hepatitis B, etc., to improve the accuracy of gene editing, reduce off-target effects, The effect of increasing flexibility

Pending Publication Date: 2022-06-03
THE THIRD AFFILIATED HOSPITAL OF SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although scientists have explored various types of therapeutic drugs later, such as: nucleotide inhibitors that inhibit the life cycle of HBV and virus nucleocapsid protein inhibitors, etc., none of them can cure chronic hepatitis B. The root cause is the existing None of the drugs can completely clear the original template HBV cccDNA for HBV replication
Once the drug is stopped, the remaining HBV cccDNA in the patient's body can replicate and express a large amount of HBV virus, which increases the difficulty of treatment of chronic HBV infection

Method used

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  • Liver-specific gene editing nano-drug as well as preparation method and application thereof
  • Liver-specific gene editing nano-drug as well as preparation method and application thereof
  • Liver-specific gene editing nano-drug as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0062] The examples of this application provide the preparation of oleic acid-modified magnetic nanoparticles (MNPs for short), and the specific methods include:

[0063] Iron acetylacetonate (2 mmol), 1,2-hexadecanediol (10 mmol), oleic acid (6 mmol), oleylamine (6 mmol), dibenzyl ether (20 mL) were combined in a three neck round bottom flask. Heated to 200°C with vigorous stirring under deoxygenation and maintained for 2h (using N 2 Bubble deoxygenation), and then continue to heat to 300 ° C, reflux for 1 h. After the reaction was completed, the temperature was sufficiently lowered to room temperature. The product was precipitated with 40 mL of ethanol, centrifuged (6000 rpm, 10 min), and finally dispersed in n-hexane for use to obtain oleic acid-modified magnetic nanoparticles (MNP for short). The morphology and elements of the synthesized nanoparticles were characterized by transmission electron microscopy, and the magnetic properties of the synthesized nanoparticles wer...

Embodiment 2

[0066] The examples of this application provide the preparation of oleic acid-modified magnetic nanoparticles (MNPs for short), and the specific methods include:

[0067] see figure 2 , figure 2 a The synthetic route of the oleic acid-modified superparamagnetic iron oxide particles provided in the examples of this application. Iron acetylacetonate (2 mmol), 1,2-hexadecanediol (10 mmol), oleic acid (6 mmol), oleylamine (6 mmol), diphenyl ether (20 mL) were combined in a three neck round bottom flask. Heat to 200°C with vigorous stirring in a deoxygenated environment and hold for 30 min (using N 2 Bubble deoxygenation), and then continue to heat to 265°C and reflux for 30min. After the reaction was completed, the temperature was sufficiently lowered to room temperature. The product was precipitated with 40 mL of ethanol, centrifuged (6000 rpm, 10 min), and finally dispersed in n-hexane for use to obtain oleic acid-modified magnetic nanoparticles (MNP for short). Particle ...

Embodiment 3

[0070] The examples of this application provide the preparation of oleic acid-modified magnetic nanoparticles (MNPs for short), and the specific methods include:

[0071] Mix the 6nm magnetic nanoparticles synthesized in Example 2, iron acetylacetonate (2mmol), 1,2-hexadecanediol (10mmol), oleic acid (2mmol), oleylamine (2mmol), and dibenzyl ether (20mL). in a three neck round bottom flask. Heat to 100°C with vigorous stirring in a deoxygenated environment and hold for 30 min (using N 2Bubble deoxygenation), then continue to heat to 200°C, reflux for 1 h, heat to 300°C and maintain for 30min. After the reaction was completed, the temperature was sufficiently lowered to room temperature. The product was precipitated with 40 mL of ethanol, centrifuged (6000 rpm, 10 min), and finally dispersed in n-hexane for use to obtain oleic acid-modified magnetic nanoparticles (MNP for short). The morphology and elements of the synthesized nanoparticles were characterized by transmission ...

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Abstract

The invention belongs to the technical field of biological medicines, and particularly relates to a liver-specific gene editing nano-drug as well as a preparation method and application thereof. The invention provides a liver-specific gene editing nano-drug. The liver-specific gene editing nano-drug comprises magnetic nanoparticles, a liver targeting ligand and a liver-specific gene editing plasmid, the liver targeting ligand is coated on the magnetic nano particles; the surfaces of the magnetic nanoparticles are positively charged; the liver-specific gene editing plasmid and the positively charged nanoparticles are self-assembled through electrostatic interaction, and the liver-specific gene editing nano-drug is obtained. The invention provides a liver-specific gene editing nano-drug as well as a preparation method and application thereof, which can realize time and space specificity of a gene editing system at a liver part and accurately treat liver diseases such as hepatitis, liver cancer, hepatic failure and hepatic fibrosis.

Description

technical field [0001] The present application belongs to the technical field of biomedicine, and particularly relates to liver-specific gene editing nanomedicines and preparation methods and applications thereof. Background technique [0002] The CRISPR gene editing system is one of the most important biological discoveries of this century. At present, the CRISPR / Cas9 system is widely used in the research of various genetic and infectious diseases, such as: cardiovascular diseases, monogenic cataract diseases, cancer, metabolic disorders, human immunodeficiency virus infection and Alzheimer's disease Wait. However, in complex biological systems, CRISPR / Cas9 gene editing still needs to be more precisely controlled in both temporal and spatial dimensions. More specifically, when using CRISPR / Cas9 gene editing, it should be avoided that the gene is edited at an unspecified time and at an untargeted location that would interfere with cell differentiation or tissue development...

Claims

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Application Information

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IPC IPC(8): A61K48/00C12N15/113C12N9/22A61P1/16A61P31/14A61P31/20
CPCA61K48/0033C12N15/1131C12N7/00C12N9/22A61P1/16A61P31/14A61P31/20C12N2730/10121C12N2310/20
Inventor 李明强陶玉卓陈雅孔慧敏易可党文涛
Owner THE THIRD AFFILIATED HOSPITAL OF SUN YAT SEN UNIV
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