A Novel Amino Lipid Series for mRNA Delivery: Improved Endosomal Escape and Sustained Pharmacology and Safety in Non-human Primates


Authors: S. Sabnis, E.S. Kumarasinghe, T. Salerno, C. Mihai, T. Ketova, J.J. Senn, A. Lynn, A. Bulychev, I. McFadyen, J. Chan, Ö. Almarsson, M.G. Stanton and K.E. Benenato

Journal: Molecular Therapy

DOI: 10.1016/j.ymthe.2018.03.010

Publication - Abstract

March 14, 2018

Nucleic Acid Lipid Nanoparticles siRNA Other Applications
The success of mRNA-based therapies depends on the availability of a safe and efficient delivery vehicle. Lipid nanoparticles have been identified as a viable option. However, there are concerns whether an acceptable tolerability profile for chronic dosing can be achieved. The efficiency and tolerability of lipid nanoparticles has been attributed to the amino lipid. Therefore, we developed a new series of amino lipids that address this concern. Clear structure-activity relationships were developed that resulted in a new amino lipid that affords efficient mRNA delivery in rodent and primate models with optimal pharmacokinetics. A 1-month toxicology evaluation in rat and non-human primate demonstrated no adverse events with the new lipid nanoparticle system. Mechanistic studies demonstrate that the improved efficiency can be attributed to increased endosomal escape. This effort has resulted in the first example of the ability to safely repeat dose mRNA-containing lipid nanoparticles in non-human primate at therapeutically relevant levels.

limit search to this category
Advanced Search

Advanced Search

close
  • Publications
  • Application Notes
  • Posters
  • Workshops
  • Videos & Webinars
  • Articles
Search

Browse by Category

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


related content

Publication - Abstract

Jun 07, 2020
Pharmaceutics

Resveratrol Enhances mRNA and siRNA Lipid Nanoparticles Primary CLL Cell Transfection

E. Kon, I. Hazan-Halevy, D. Rosenblum, N. Cohen, S. Chatterjee, N. Veiga, P. Raanani, O. Bairey, O. Benjamini, A. Nagler and D. Peer

Oncology Targeted Drug Delivery Nucleic Acid Lipid Nanoparticles
Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Western populations. Therapies such as mRNA and siRNA encapsulated in lipid nanoparticles (LNPs) represent a clinically advanced platform and are utilized for a wide variety of applications. Unfortunately, tr...
Read More


Publication - Abstract

Aug 05, 2016
Journal of Drug Targeting

Microfluidics: A Transformational Tool for Nanomedicine Development and Production

S. Garg, G. Heuck, S. Ip, E. Ramsay

Small Molecule Drugs mRNA siRNA

Microfluidic devices are mircoscale fluidic circuits used to manipulate liquids at the nanoliter scale. The ability to control the mixing of fluids and the continuous nature of the process make it apt for solvent/antisolvent precipitation of drug-d...

Read More


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