biostudies-literatureUnknown15(1)Renzi SLipid nanoparticles (LNPs) play a crucial role in addressing genetic disorders, and cancer, and combating pandemics such as COVID-19 and its variants. Yet, the ability of LNPs to effectively encapsulate large-size DNA molecules remains elusive. This is a significant limitation, as the successful delivery of large-size DNA holds immense potential for gene therapy. To address this gap, the present study focuses on the design of PEGylated LNPs, incorporating large-sized DNA, departing from traditional RNA and ionizable lipids. The resultant LNPs demonstrate a unique particle morphology. These particles were further engineered with a DNA coating and plasma proteins. This multicomponent bionanoconstruct exhibits enhanced transfection efficiency and safety in controlled laboratory settings and iNature communications9119https://www.ebi.ac.uk/biostudies/studies/S-EPMC11496629biostudies-literatureStructuring lipid nanoparticles, DNA, and protein corona into stealth bionanoarchitectures for in vivo gene delivery.PMC11496629Renzi SPozzi DPesce LCardarelli FMancusi ADigiacomo LRossi MDe Lorenzi VMontone CMMura FNatiello BAmenitsch HLaura Capriotti ALagana AChecquolo SQuagliarini EParisi GPignataro MGZingoni ACanettieri GGiuli MVLoconte LNicoletti CVulpis EDi Magno LGhignoli SCaracciolo GfalseStructuring lipid nanoparticles, DNA, and protein corona into stealth bionanoarchitectures for in vivo gene delivery.Lipid nanoparticles (LNPs) play a crucial role in addressing genetic disorders, and cancer, and combating pandemics such as COVID-19 and its variants. Yet, the ability of LNPs to effectively encapsulate large-size DNA molecules remains elusive. This is a significant limitation, as the successful delivery of large-size DNA holds immense potential for gene therapy. To address this gap, the present study focuses on the design of PEGylated LNPs, incorporating large-sized DNA, departing from traditional RNA and ionizable lipids. The resultant LNPs demonstrate a unique particle morphology. These particles were further engineered with a DNA coating and plasma proteins. This multicomponent bionanoconstruct exhibits enhanced transfection efficiency and safety in controlled laboratory settings and i2024-01-01T00:00:00Z2024 Oct2026-07-15T08:11:58.534Z2025-04-06T22:45:40.121ZS-EPMC114966293943848410.1038/s41467-024-53569-8