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

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

SUBMITTER: Tanaka H 

PROVIDER: S-EPMC8070490 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature