April 13, 2021
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.
Publication - Summary
Apr 23, 2015
Cell
In this paper, the MacVicar Lab used Neuro9 siRNA cell transfection nanoparticles (Neuro9-siRNA) prepared using the NanoAssemblrTM Benchtop instrument to uncover the role of a specific chloride channel in cytotoxic edema, which is a...
Publication - Abstract
Feb 15, 2021
Molecular Therapy Nucleic Acids