Structuring lipid nanoparticles, DNA, and protein corona into stealth bionanoarchitectures for in vivo gene delivery.

Autor: Renzi S; Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy., Digiacomo L; Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy., Pozzi D; Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy., Quagliarini E; Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy., Vulpis E; Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy., Giuli MV; Department of Medico-Surgical Sciences and Biotechnology, Sapienza University of Rome, Laboratory affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Latina, Italy., Mancusi A; Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy., Natiello B; Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy., Pignataro MG; Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Rome, Italy., Canettieri G; Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy., Di Magno L; Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy., Pesce L; NEST, Scuola Normale Superiore, Pisa, Italy., De Lorenzi V; NEST, Scuola Normale Superiore, Pisa, Italy., Ghignoli S; NEST, Scuola Normale Superiore, Pisa, Italy., Loconte L; Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy., Montone CM; Department of Chemistry, Sapienza University of Rome, Rome, Italy., Laura Capriotti A; Department of Chemistry, Sapienza University of Rome, Rome, Italy., Laganà A; Department of Chemistry, Sapienza University of Rome, Rome, Italy., Nicoletti C; Unit of Histology and Medical Embryology, Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University of Rome, Rome, Italy., Amenitsch H; Institute of Inorganic Chemistry, Graz University of Technology, Graz, Austria., Rossi M; Department of Basic and Applied Sciences for Engineering and Center for Nanotechnology Applied to Engineering (CNIS), Sapienza University of Rome, Rome, Italy., Mura F; Department of Basic and Applied Sciences for Engineering and Center for Nanotechnology Applied to Engineering (CNIS), Sapienza University of Rome, Rome, Italy., Parisi G; Department of Basic and Applied Sciences for Engineering and Center for Nanotechnology Applied to Engineering (CNIS), Sapienza University of Rome, Rome, Italy., Cardarelli F; NEST, Scuola Normale Superiore, Pisa, Italy., Zingoni A; Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy. alessandra.zingoni@uniroma1.it., Checquolo S; Department of Medico-Surgical Sciences and Biotechnology, Sapienza University of Rome, Laboratory affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Latina, Italy. saula.checquolo@uniroma1.it., Caracciolo G; Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy. giulio.caracciolo@uniroma1.it.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Oct 23; Vol. 15 (1), pp. 9119. Date of Electronic Publication: 2024 Oct 23.
DOI: 10.1038/s41467-024-53569-8
Abstrakt: 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 improved immune system evasion in in vivo tests. These findings provide valuable insights for the design and development of bionanoarchitectures for large-size DNA delivery, opening new avenues for transformative gene therapies.
(© 2024. The Author(s).)
Databáze: MEDLINE
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