title: Effects of local structural transformation of lipid-like compounds on delivery of messenger RNA.
abstract: Lipid-like nanoparticles (LLNs) have shown great potential for RNA delivery. Lipid-like compounds are key components in LLNs. In this study, we investigated the effects of local structural transformation of lipid-like compounds on delivery of messenger RNA. Our results showed that position change of functional groups on lipid-like compounds can dramatically improve delivery efficiency. We then optimized formulation ratios of TNT-b10 LLNs, a lead material, increasing delivery efficiency over 2-fold. More importantly, pegylated TNT-b10 LLNs is stable for over four weeks and is over 10-fold more efficient than that of its counterpart TNT-a10 LLNs. Additionally, the optimal formulation O-TNT-b10 LLNs is capable of delivering mRNA encoding luciferase in vivo. These results provide useful insights into the design of next generation LLNs for mRNA delivery.
authors.affiliation: Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Xiao
authors.initials: X
authors.lastname: Luo
authors.affiliation: Center for Electron Microscopy and Analysis, Department of Materials Science and Engineering, The Ohio State University, Columbus, Ohio 43212, USA.
authors.forename: Binbin
authors.initials: B
authors.lastname: Deng
authors.affiliation: Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: JoLynn B
authors.initials: JB
authors.lastname: Giancola
authors.affiliation: Center for Electron Microscopy and Analysis, Department of Materials Science and Engineering, The Ohio State University, Columbus, Ohio 43212, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: McComb
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida 32610, USA.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Schmittgen
authors.affiliation: Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Yizhou
authors.initials: Y
authors.lastname: Dong
mesh_terms: D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000008:administration & dosage*; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008156:Luciferases / Q000008:administration & dosage* / Q000235:genetics*; D053758:Nanoparticles / Q000008:administration & dosage; D012333:RNA, Messenger / Q000008:administration & dosage* / Q000235:genetics*
chemical_list: D004337:Drug Carriers; D008055:Lipids; D012333:RNA, Messenger; D008156:Luciferases