Delivery of Oligonucleotides Using a Self-Degradable Lipid-Like Material


Authors: H. Tanaka, N. Takata, Y. Sakurai, H. Akita et. al.

Journal: Pharmaceutics

DOI: 10.3390/pharmaceutics13040544

Publication - Abstract

April 13, 2021

Abstract

The world-first success of lipid nanoparticle (LNP)-based siRNA therapeutics (ONPATTRO®) promises to accelerate developments in siRNA therapeutics/gene therapy using LNP-type drug delivery systems (DDS). In this study, we explore the optimal composition of an LNP containing a self-degradable material (ssPalmO-Phe) for the delivery of oligonucleotides. siRNA or antisense oligonucleotides (ASO) were encapsulated in LNP with different lipid compositions. The hepatic knockdown efficiency of the target genes and liver toxicity were evaluated. The optimal compositions for the siRNA were different from those for ASO, and different from those for mRNA that were reported in a previous study. Extracellular stability, endosomal escape and cellular uptake appear to be the key processes for the successful delivery of mRNA, siRNA and ASO, respectively. Moreover, the compositions of the LNPs likely contribute to their toxicity. The lipid composition of the LNP needs to be optimized depending on the type of nucleic acids under consideration if the applications of LNPs are to be further expanded.

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 - Summary

Systemic Delivery of Factor IX Messenger RNA for Protein Replacement Therapy

S. Ramaswamy, N. Tonnu, K. Tachikawa, P. Limphong, J.B. Vega, P.P. Karmali, P. Chivukula, and I.M. Verma

Like most genetic disorders, Hemophilia B is caused by a mutation that leads to a dysfunctional protein. Hemophilia B patients are susceptible to life threatening bleeds when injured due to a clotting defect caused by a mutated coagulation fac...

Read More


Publication - Abstract

Design of SARS-CoV-2 hFc-Conjugated Receptor-Binding Domain mRNA Vaccine Delivered via Lipid Nanoparticles

U. Elia, S. Ramishetti, R. Rosenfield, N. Dammes, E. Bar-Haim, G. S. Naidu, E. Makdasi, Y. Yahalom-Ronen, H. Tamir, N. Paran, O. Cohen and D. Peer

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified as the causal agent of COVID-19 and stands at the center of the current global human pandemic, with death toll exceeding one million. The urgent need for a vaccine has led to the development of vario...
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.