Microfluidic Synthesis of Highly Potent Limit-size Lipid Nanoparticles for in Vivo Delivery of siRNA


Authors: N.M. Belliveau, J. Huft, P.J. Lin, S. Chen, A.K. Leung, T.J. Leaver, A.W. Wild, J.B. Lee, R.J. Taylor, Y.K. Tam, C.L. Hansen, and P.R. Cullis

Journal: Molecular Therapy: Nucleic Acids

DOI: 10.1038/mtna.2012.28

Publication - Abstract

August 14, 2012

Abstract:

Lipid nanoparticles (LNP) are the leading systems for in vivo delivery of small interfering RNA (siRNA) for therapeutic applications. Formulation of LNP siRNA systems requires rapid mixing of solutions containing cationic lipid with solutions containing siRNA. Current formulation procedures employ macroscopic mixing processes to produce systems 70-nm diameter or larger that have variable siRNA encapsulation efficiency, homogeneity, and reproducibility. Here, we show that microfluidic mixing techniques, which permit millisecond mixing at the nanoliter scale, can reproducibly generate limit size LNP siRNA systems 20 nm and larger with essentially complete encapsulation of siRNA over a wide range of conditions with polydispersity indexes as low as 0.02. Optimized LNP siRNA systems produced by microfluidic mixing achieved 50% target gene silencing in hepatocytes at a dose level of 10 µg/kg siRNA in mice. We anticipate that microfluidic mixing, a precisely controlled and readily scalable technique, will become the preferred method for formulation of LNP siRNA delivery systems.

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
    • 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

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

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

Oligonucleotide is emerging as a novel class of therapeutics due to its high specificity, and ability to manage the incorrigible diseases with targeted action. The expedited growth evident from past few decades unveils the potentiality of the oligonucleotide as the future medicin...
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.