Synthetic Lipid Particle Models Elucidate Lipid–Lipid Interactions Underlying LNP-Membrane Fusion

Shu Okumura – Specialist, Toshiba Corporation; Nao Kobayashi – Specialist, Toshiba Corporation; Kohei Miyata – Specialist, Toshiba Corporation; Jin Machida – Employee, Toshiba Corporation; Masaaki Takada – Expert, Toshiba Corporation; Mitsuko Sugano – Senior Fellow, Toshiba Corporation

Introduction: Previous studies have shown that AI‑guided lipid optimization enables the rational design of cell‑targeted LNPs (1). We also demonstrated that tropism is influenced not only by LNP composition but also by the lipid compositions of target cell membranes, using small unilamellar vesicles (SUVs) as models (2). This SUV–LNP model recapitulates LNP–cell interactions, reproducing uptake trends (Fig.1A) and maintaining LNP internalization even when endocytic pathways were suppressed (Fig.1B). In this study, we expanded the range of LNPs and SUVs to identify lipid components that modulate fusion behavior.