Novel Ionizable Lipids Enable DoE-Optimized Lipid Nanoparticles for pDNA Delivery
Ana Clara Silva – BSc, Federal University of Minas Gerais; Gabriel Azevedo – Undergraduate Student, Federal University of Minas Gerais; Pedro Guimaraes – PhD - professor, Federal University of Minas Gerais
Dr. Federal University of Minas Gerais, Minas Gerais, Brazil
Introduction: Ionizable lipids are central to lipid nanoparticle (LNP) performance for nucleic acid delivery, yet structure–activity relationships remain incompletely understood, limiting the rational design of next-generation systems1. Subtle variations in hydrophobic tail length can strongly influence transfection efficiency, cell viability, biodistribution, and intracellular delivery mechanisms such as endosomal escape2. This study evaluates how systematic structural modifications in novel ionizable lipids impact LNP physicochemical properties and DNA delivery performance.
Learning Objectives:
Understand how structurally novel ionizable lipids can enhance LNP-mediated DNA delivery.
Recognize the high transfection performance achieved with the newly developed lipids in HepG2 cells.
Learn how DoE optimizes LNP composition for efficient pDNA delivery.
