Rational design and modular synthesis of biodegradable ionizable lipids via the Passerini reaction for mRNA delivery.

ABSTRACT: The ionizable lipid component of lipid nanoparticle (LNP) formulations is essential for mRNA delivery by facilitating endosomal escape. Conventionally, these lipids are synthesized through complex, multistep chemical processes that are both time-consuming and require significant engineering. Furthermore, the development of new ionizable lipids is hindered by a limited understanding of the structure-activity relationships essential for effective mRNA delivery. In this work, we have developed a modular platform utilizing the Passerini reaction to rapidly generate large, chemically diverse libraries of biodegradable ionizable lipids. This high-throughput approach enables the systematic exploration of various lipid components-head groups, tails, and spacers-and their impacts on mRNA delivery e

SUBMITTER: Xu Y 

PROVIDER: S-EPMC11804478 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature