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 - Abstract
Jan 15, 2016
Therapeutic Delivery
Delivery of therapeutic nucleic acids in general and small interfering RNAs (siRNAs) in particular although a relatively nascent area of research, has already overcome several technical and regulatory hurdles over past few years.
Publication - Abstract
Aug 03, 2020
Vaccines
In this in vitro and in vitro study, the Yoshioka lab at Osaka University investigated cytosine–phosphate–guanine oligodeoxynucleotides (CpG ODN) lipid nanoparticles (LNPs) as an adjuvant for seasonal split vaccines (SV) from influenza virus antig...