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MRNA nucleic acid drug intracellular delivery system, preparation method and application

A delivery system and drug technology, applied in the field of medicine and biology, can solve the problems of incapable of large-scale clinical application, poor stability, low intracellular delivery efficiency, etc., achieve stable intracellular delivery efficiency, high efficiency delivery efficiency, increase stability and mRNA Effect of transfection efficiency

Inactive Publication Date: 2020-07-31
深圳市新合生物医疗科技有限公司
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0007] The purpose of the present invention is to provide a composition, preparation method and preparation process for efficient loading and effective intracellular delivery of mRNA nucleic acid drugs, so as to solve the problem of poor stability of existing mRNA nucleic acid drugs, low intracellular delivery efficiency, and inability to Practical problems such as large-scale clinical application

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  • MRNA nucleic acid drug intracellular delivery system, preparation method and application
  • MRNA nucleic acid drug intracellular delivery system, preparation method and application
  • MRNA nucleic acid drug intracellular delivery system, preparation method and application

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Embodiment

[0063] The intracellular delivery system of mRNA nucleic acid drugs prepared in the present invention has the principle of action as follows: figure 1 shown. The mRNA nucleic acid drug delivery system is a complex formed by wrapping and loading mRNA nucleic acid drugs with lipid nanoparticles. The lipid nanoparticles are derived from ionizable cationic lipids, phospholipid auxiliary lipids, cholesterol, and phospholipid polyethylene glycol. The 4 components are composed in certain proportions. Among them, ionizable cationic lipids contain monovalent or multivalent amino cations, and these amino cations can electrostatically interact with negatively charged mRNA molecules to concentrate and load mRNA; Changes are relatively sensitive, which helps lipid nanoparticles to escape from late inclusion bodies (effectively transport mRNA nucleic acid drugs into target cells and release them in the acidic environment of late inclusion bodies at a specific pH of target cells, so that nu...

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Abstract

The invention discloses an mRNA nucleic acid drug delivery system, a preparation method and application. The system comprises lipid nanoparticles used for loading one or more mRNAs, and the lipid nanoparticles are prepared from raw materials including ionizable cationic lipid, phospholipid auxiliary lipid, cholesterol and phospholipid polyethylene glycol derivatives. According to the non-viral-vector mRNA nucleic acid drug targeting intracellular delivery system, mRNA is concentrated and loaded through the electrostatic interaction of ionizable cationic lipid and the mRNA, the phospholipid auxiliary lipid component-mediated pH sensitivity and advanced inclusion escape can enable an mRNA nucleic acid drug to be efficiently delivered to target cells, and the mRNA nucleic acid drug is released to cytoplasm of the target cells to play a pharmacodynamic role. The phospholipid auxiliary lipid increases the advanced inclusion escape ability of the mRNA / lipid nanoparticles, and increases the stability of the mRNA / lipid nanoparticles and the mRNA transfection efficiency. The system has efficient and stable mRNA drug intracellular delivery efficiency, and significantly improves the prevention and treatment effects of mRNA nucleic acid drugs.

Description

technical field [0001] The invention belongs to the field of medicine and biology, and in particular relates to a non-viral carrier-based mRNA nucleic acid drug intracellular delivery system, preparation method and application that can be produced and applied on a large scale. Background technique [0002] mRNA (messenger ribonucleic acid) is composed of one strand of DNA (deoxyribonucleic acid) as a template, under the catalysis of RNA polymerase (RNA polymerase), four ribonucleoside triphosphates (A, U, G, C) as substrates, a type of single-stranded ribonucleic acid polymerized through phosphodiester bonds. mRNA can carry and transmit genetic information stored in DNA in the nucleus, and plays a key role in the conversion of genetic information into functional proteins. In the cytoplasm, immature mRNA is processed and modified into mature mRNA through capping, tailing, and intron cleavage steps, and mature mRNA can precisely guide the protein synthesis process in the cyto...

Claims

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Application Information

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IPC IPC(8): A61K9/51A61K47/18A61K47/24A61K47/28A61K31/7105A61P31/00A61P35/00A61P3/10A61P9/00
CPCA61K9/5123A61K9/5146A61K31/7105A61P3/10A61P9/00A61P31/00A61P35/00A61K9/0019A61K9/1272A61K9/5192A61K47/24B82Y5/00A01K2217/05
Inventor 潘有东刘刚王奕肖安万季文颖宋麒
Owner 深圳市新合生物医疗科技有限公司
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