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Ionizable lipid molecule, preparation method thereof, and application of ionizable lipid molecule in preparation of lipid nanoparticles

A lipid nanoparticle and molecular technology, applied in nanotechnology, nanotechnology, nanomedicine, etc., can solve the problems of not being able to fully exert the efficacy of mRNA-LNP preparations, achieve excellent mRNA carrier performance, and improve the effect of translation and expression levels

Active Publication Date: 2021-06-15
IMMORNA (HANGZHOU) BIOTECHNOLOGY CO LTD
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  • Abstract
  • Description
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  • Application Information

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Problems solved by technology

The existing LNP component scheme cannot fully exert the effectiveness of the mRNA-LNP preparation, and it is necessary to continuously adjust the structure of ionizable lipid molecules and optimize the design of specific RNA. The present invention solves such problems

Method used

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  • Ionizable lipid molecule, preparation method thereof, and application of ionizable lipid molecule in preparation of lipid nanoparticles
  • Ionizable lipid molecule, preparation method thereof, and application of ionizable lipid molecule in preparation of lipid nanoparticles
  • Ionizable lipid molecule, preparation method thereof, and application of ionizable lipid molecule in preparation of lipid nanoparticles

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Embodiment Construction

[0032] The present invention will be specifically introduced below in conjunction with the accompanying drawings and specific embodiments.

[0033] An ionizable lipid molecule with a chemical structural formula: (Code: XH-04).

[0034] The following abbreviations represent the following reagents respectively:

[0035] DCM: dichloromethane; DMAP: 4-dimethylaminopyridine; TEA: triethanolamine, EDCI: 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride; TLC: silica gel plates Thin layer chromatography; THF: tetrahydrofuran; DMF dimethylformamide; DSPC: 1,2-distearate-sn-glycerophosphatidylcholine, DOPE: 1,2-dioleoyl-sn-glycerol-3- Phosphoethanolamine, TFF: Tangential Flow Filtration.

[0036] A preparation method of ionizable lipid molecules such as figure 1 Shown; specifically include the following steps:

[0037] Step 1, compound 1 in DCM dichloromethane (100mL) (20.0g, 89.6mmol, 1.00 equiv) was added to the solution of compound 1A (14.2 g, 98.6 mmol, 1.10 equiv)...

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Abstract

The invention discloses an ionizable lipid molecule, a preparation method thereof, and application of the ionizable lipid molecule in the preparation of lipid nanoparticles. The ionizable lipid molecule has a chemical structure shown in the description with the code name being XH-04; the novel ionizable lipid molecule XH-04, phospholipid, cholesterol and polyethylene glycol are subjected to microfluidic synthesis to obtain the LNP, the obtained LNP can improve the translation expression level of a load, namely mRNA, in cells, the action efficacy of an mRNA-LNP preparation is improved, and a theoretical basis is provided for theoretical treatment of a personalized mRNA-LNP preparation.

Description

technical field [0001] The invention relates to the field of biotechnology, in particular to an ionizable lipid molecule and its preparation method and its application in the preparation of lipid nanoparticles. Background technique [0002] Nucleic acids (RNA) have great therapeutic potential in modulating protein expression in vivo, but naked RNA is internalized by cells with extremely low efficiency, and it is easily cleared by the kidney during in vivo delivery, or quickly by RNases in vivo. Degradation, its actual curative effect is greatly reduced. In order to exert the therapeutic ability of RNA more safely and effectively, scientists use lipid nanoparticles (LNP) to encapsulate and deliver RNA to specific parts of the body. This RNA delivery strategy has shown great utility in the delivery of double-stranded small interfering RNAs (siRNAs, 21 to 23 nucleotides in length). For example, lipidoid C12-200 has been widely used to make siRNA-LNP preparations for various t...

Claims

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Application Information

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IPC IPC(8): C07C229/12C07C227/18A61K9/51A61K47/18A61K31/7088B82Y5/00B82Y40/00
CPCC07C229/12C07C227/18C07C67/31C07C67/08A61K9/5123A61K31/7088B82Y5/00B82Y40/00C07C69/712C07C69/63
Inventor 王子豪
Owner IMMORNA (HANGZHOU) BIOTECHNOLOGY CO LTD
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