title: An Orthogonal Array Optimization of Lipid-like Nanoparticles for mRNA Delivery in Vivo.
abstract: Systemic delivery of mRNA-based therapeutics remains a challenging issue for preclinical and clinical studies. Here, we describe new lipid-like nanoparticles (TT-LLNs) developed through an orthogonal array design, which demonstrates improved delivery efficiency of mRNA encoding luciferase in vitro by over 350-fold with significantly reduced experimental workload. One optimized TT3 LLN, termed O-TT3 LLNs, was able to restore the human factor IX (hFIX) level to normal physiological values in FIX-knockout mice. Consequently, these mRNA based nanomaterials merit further development for therapeutic applications.
authors.affiliation: Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University , Columbus, Ohio 43210, United States.
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, United States.
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, United States.
authors.forename: Binbin
authors.initials: B
authors.lastname: Deng
authors.affiliation: Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University , Columbus, Ohio 43210, United States.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Center for Electron Microscopy and Analysis, Department of Materials Science and Engineering, The Ohio State University , Columbus, Ohio 43212, United States.
authors.forename: David W
authors.initials: DW
authors.lastname: McComb
authors.affiliation: Department of Medicine, University of California-San Francisco , San Francisco, California 94143, United States.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Medicine, University of California-San Francisco , San Francisco, California 94143, United States.
authors.forename: Karin M L
authors.initials: KM
authors.lastname: Gaensler
authors.affiliation: Tsinghua-Peking Center for Life Sciences, School of Medicine, Tsinghua University , Beijing 100084, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Tan
authors.affiliation: Division of Hematology/Oncology/BMT, Nationwide Children's Hospital , Columbus, Ohio 43205, United States.|Department of Pediatrics, College of Medicine, The Ohio State University , Columbus, Ohio 43205, United States.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Dunn
authors.affiliation: Division of Hematology/Oncology/BMT, Nationwide Children's Hospital , Columbus, Ohio 43205, United States.|Department of Pediatrics, College of Medicine, The Ohio State University , Columbus, Ohio 43205, United States.|Center for Clinical and Translational Research, The Research Institute at Nationwide Children's Hospital , Columbus, Ohio 43205, United States.
authors.forename: Bryce A
authors.initials: BA
authors.lastname: Kerlin
authors.affiliation: Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University , Columbus, Ohio 43210, United States.
authors.forename: Yizhou
authors.initials: Y
authors.lastname: Dong
mesh_terms: D006801:Humans; D008055:Lipids / Q000737:chemistry*; D053758:Nanoparticles; D012333:RNA, Messenger / Q000008:administration & dosage*
chemical_list: D008055:Lipids; D012333:RNA, Messenger
keywords: Lipid-like nanoparticles; genetic disorders; hemophilia; mRNA delivery; orthogonal array design