Formulation and Characterization of Novel Ionizable and Cationic Lipid Nanoparticles for the Delivery of Splice-Switching Oligonucleotides.

ABSTRACT: Despite increasing knowledge about the mechanistic aspects of lipid nanoparticles (LNPs) as oligonucleotide carriers, the structure-function relationship in LNPs has been generally overlooked. Understanding this correlation is critical in the rational design of LNPs. Here, a materials characterization approach is utilized, applying structural information from small-angle X-ray scattering experiments to design novel LNPs focusing on distinct lipid organizations with a minimal compositional variation. The lipid phase structures are characterized in these LNPs and their corresponding bulk lipid mixtures with small-angle scattering techniques, and the LNP-cell interactions in vitro with respect to cytotoxicity, hemolysis, cargo delivery, cell uptake, and lysosomal swelling. An LNP is identifie

SUBMITTER: Ojansivu M 

PROVIDER: S-EPMC12038542 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature