Deconvoluting Lipid Nanoparticle Structure for Messenger RNA Delivery


Authors: Y. Eygeris, S. Patel, A. Jozic and G. Sahay

Journal: Nano Letters

DOI: 10.1021/acs.nanolett.0c01386

Publication - Abstract

May 06, 2020

Abstract

Lipid nanoparticle (LNP) packaged mRNA vaccines have been deployed against infectious diseases such as COVID-19, yet their structural features remain unclear. Cholesterol, a major constituent within LNPs, contributes to their morphology that influences gene delivery. Herein, we examine the structure of LNPs containing cholesterol derivatives using electron microscopy, differential scanning calorimetry, and membrane fluidity assays. LNPs formulated with C24 alkyl derivatives of cholesterol show a polymorphic shape and various degrees of multilamellarity and lipid partitioning, likely due to phase separation. The addition of methyl and ethyl groups to the C24 alkyl tail of the cholesterol backbone induces multilamellarity (>50% increase compared to cholesterol), while the addition of a double bond induces lipid partitioning (>90% increase compared to cholesterol). LNPs with multilamellar and faceted structures, as well as a lamellar lipid phase, showed higher gene transfection. Unraveling the structure of mRNA-LNPs can enable their rational design toward enhanced gene delivery.

Advanced Search

close
  • Publications
  • Application Notes
  • Posters
  • Workshops
  • Videos & Webinars
  • Blog Posts
Search

Browse by Category

  • Application
    • Diagnostic and Imaging
    • Genetic Medicine
    • Hematology
    • Metabolic Disorders
    • Neuroscience
    • Oncology
    • Skeletal Disorders
    • Targeted Drug Delivery
    • Vaccines
    • Other Applications
  • Formulation
    • Liposomes
    • Nucleic Acid Lipid Nanoparticles
    • Polymeric Nanoparticles
    • Other Formulations
  • Payload
    • DNA
    • microRNA
    • mRNA
    • siRNA
    • Small Molecule Drugs
    • Other Payloads


related content

Publication - Abstract

Lipid-like nanoparticles (LLNs) have shown great promise for nucleic acid delivery. Recently, we have developed N1,N3,N5-tris(2-aminoethyl)benzene-1,3,5-tricarboxamide (TT) derived li...

Read More


Publication - Abstract

Microfluidic-Based Manufacture of siRNA-Lipid Nanoparticles for Therapeutic Applications

C. Walsh, K. Ou, N.M. Belliveau, T.J. Leaver, A.W. Wild, J. Huft, P.J. Lin, S. Chen, A.K. Leung, J.B. Lee, C.L. Hansen, R.J. Taylor, E.C. Ramsay and P.R Cullis

A simple, efficient, and scalable manufacturing technique is required for developing siRNA-lipid nanoparticles (siRNA-LNP) for therapeutic applications.

Read More


Stay Informed

Sign up today to automatically receive new Precision NanoSystems application notes, conference posters, relevant science publications, and webinar invites.

MENU
菜单
X
X