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Title [sv]
Lipidnanopartikel – proteininteraktioner: Formuleringsoptimering för bättre terapeutisk effekt
Abstract [sv]

Om projektet

Detta projekt syftar till att förstå hur LNP:s sammansättning och struktur bidrar till LNP:s proteinbindningskapacitet och att reda ut hur LNP tas upp av celler, vilket är nyckeln till att designa LNP:er som selektivt kan rikta in sig på organ.

Affilierade: Marianna Yanez Arteta, Astra Zeneca AB och Lennart Lindfors, Astra Zeneca AB.

Läs mer i den engelskspråkiga beskrivningen.

Abstract [en]

About the project

Therapeutic treatments based on the production of proteins by delivering messenger RNA (mRNA) represent a promising approach to treating many diseases that currently lack other alternatives. However, one of the major challenges is to protect these macromolecules from enzymatic degradation and deliver them to the target cells. Lipid nanoparticles (LNPs) formed by a cationic ionisable lipid (CIL), DSPC, cholesterol (Chol) and a pegylated (PEG) lipid have been approved by FDA for delivery of small interference RNA (siRNA) for the treatment of peripheral nerve disease. Nevertheless, there are still concerns about these nanoparticles' safety profile.

A good understanding of the physical and chemical characteristics of the LNPs under study is necessary to progress from pre-clinical testing. In addition, the biodistribution and cellular uptake of LNPs are affected by their surface composition as well as by the extracellular proteins present at the site of LNPs administration, such as proteins in the plasma. Therefore, it is also important to understand the relation between LNP physical-chemical properties and their ability to collect proteins from the plasma.

A common component found in the “protein corona” of LNPs is Apolipoprotein E (ApoE), which is responsible for the transport of fats in the systemic circulation and it triggers the fat uptake by cell-rich in low-density lipoprotein (LDL) receptors. This recognition step is critical to controlling the LNP’s circulation time and thus its pharmacological efficiency.

This project aims to understand how LNP composition and structure contribute to the LNP’s protein binding capacity and to unravel how LNP are taken up by cells, which is key to designing LNPs that can selectively target organs.

Affiliated: Marianna Yanez Arteta, Astra Zeneca AB and Lennart Lindfors, Astra Zeneca AB.

Co-InvestigatorSebastiani, Federica
Co-InvestigatorCárdenas, Marité
Co-InvestigatorBjörklund, Sebastian
Co-InvestigatorRuzgas, Tautgirdas
Coordinating organisation
Malmö University, Biofilms Research Center for Biointerfaces
2019-01-01 - 2021-12-31
Keywords [sv]
proteiner, proteinbindning, lipider
National Category
Biomedical Laboratory Science/Technology
DiVA, id: project:2754

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