Synthesis and Biological Evaluation of Ionizable Lipid Materials for the In Vivo Delivery of Messenger RNA to B Lymphocytes

Synthesis and Biological Evaluation of Ionizable Lipid Materials for the In Vivo Delivery of Messenger RNA to B Lymphocytes

© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bibliographische Detailangaben
Veröffentlicht in:Advanced materials (Deerfield Beach, Fla.). - 1998. - 29(2017), 33 vom: 01. Sept.
1. Verfasser: Fenton, Owen S (VerfasserIn)
Weitere Verfasser: Kauffman, Kevin J, Kaczmarek, James C, McClellan, Rebecca L, Jhunjhunwala, Siddharth, Tibbitt, Mark W, Zeng, Manhao D, Appel, Eric A, Dorkin, Joseph R, Mir, Faryal F, Yang, Jung H, Oberli, Matthias A, Heartlein, Michael W, DeRosa, Frank, Langer, Robert, Anderson, Daniel G
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2017
Zugriff auf das übergeordnete Werk:Advanced materials (Deerfield Beach, Fla.)
Schlagworte:Journal Article RNA biomaterials drug delivery nanoparticles proteins Lipids RNA, Messenger
Beschreibung
Zusammenfassung:© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
B lymphocytes regulate several aspects of immunity including antibody production, cytokine secretion, and T-cell activation; moreover, B cell misregulation is implicated in autoimmune disorders and cancers such as multiple sclerosis and non-Hodgkin's lymphomas. The delivery of messenger RNA (mRNA) into B cells can be used to modulate and study these biological functions by means of inducing functional protein expression in a dose-dependent and time-controlled manner. However, current in vivo mRNA delivery systems fail to transfect B lymphocytes and instead primarily target hepatocytes and dendritic cells. Here, the design, synthesis, and biological evaluation of a lipid nanoparticle (LNP) system that can encapsulate mRNA, navigate to the spleen, transfect B lymphocytes, and induce more than 60 pg of protein expression per million B cells within the spleen is described. Importantly, this LNP induces more than 85% of total protein production in the spleen, despite LNPs being observed transiently in the liver and other organs. These results demonstrate that LNP composition alone can be used to modulate the site of protein induction in vivo, highlighting the critical importance of designing and synthesizing new nanomaterials for nucleic acid delivery
Beschreibung:Date Completed 22.01.2019
Date Revised 30.09.2020
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-4095
DOI:10.1002/adma.201606944