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Improved lipid-peptide nanocomplex formulation for mRNA delivery to cells

A compound and cell technology, applied in the direction of recombinant DNA technology, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., can solve the problems of low protein expression level, lack, poor storage stability, etc.

Pending Publication Date: 2020-08-28
UCL BUSINESS PLC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0012] To date, the lack of effective vectors has limited the delivery of messenger RNA (mRNA) to cells in a non-viral manner
Attempts to deliver mRNA using non-viral vectors known to have been used for DNA or siRNA, resulting in suboptimal protein expression
In addition, known non-viral vectors have poor storage stability when packaged with mRNA

Method used

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  • Improved lipid-peptide nanocomplex formulation for mRNA delivery to cells
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  • Improved lipid-peptide nanocomplex formulation for mRNA delivery to cells

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Embodiment

[0097] Experimental Methods and Techniques

[0098] General Experimental Methods and Techniques

[0099]Solvents and reagents used for syntheses were of reagent grade from commercial suppliers and used without further purification unless otherwise stated. Dry CH was obtained using an anhydrous alumina column following the procedure described in Pangborn, A.B.; Giardello, M.A.; Grubbs, R.H.; Rosen, R.K.; 2 Cl 2 . All moisture-sensitive reactions were performed under a nitrogen or argon atmosphere using oven-dried glassware. Pass at Kieselgel 60 F 254 The reaction was monitored by TLC on the plate and detected by UV, potassium permanganate and phosphomolybdic acid staining. Flash column chromatography was performed using silica gel (particle size 40-63 μm). Recorded on Bruker AMX300MHz, Avance-500MHz and Avance-600MHz machines 1 H NMR and 13 C NMR spectrum. Coupling constants are measured in Hertz (Hz) and spectra were collected at 298K unless otherwise stated. Mass ...

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Abstract

A liposome comprising a cationic lipid, a phospholipid and a peptide and optionally consisting of from 20 to 50% by molarity cholesterol, based on the total amount of lipids,for use in non-viral genedelivery systems, for example,in the formation of lipopolyplex transfection vectors for the delivery of mRNA to cells.

Description

technical field [0001] The present invention relates to formulations of lipids and peptides suitable for the delivery of biologically active substances such as nucleic acids, especially mRNA, to cells. The invention further relates to transfection complexes used as non-viral vectors for the delivery of biologically active substances such as mRNA to cells, and the use of such complexes eg in prophylaxis, therapy and vaccination or in vitro laboratory settings. Background technique [0002] Gene delivery for therapeutic or other purposes is well known, especially for the treatment of diseases such as cystic fibrosis and certain cancers. The term refers to the delivery of a gene or part of a gene into a cell to correct certain defects. In this specification, the term is also used to refer to the introduction of nucleic acid material into target cells, and includes both genetic vaccination and the in vitro production of commercially usable proteins in so-called cell factories. ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/00A61K9/127A61K48/00A61K47/64A61K38/16
CPCA61K9/0019A61K9/1272A61K9/1277A61K47/6455A61K47/543A61K47/6911A61K39/00C12N15/88C07K7/06C07K7/08C07K2319/74A61K48/00
Inventor D·格兰特-塞鲁克S·L·哈特
Owner UCL BUSINESS PLC
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