July 20, 2017
RNA is emerging as a potential therapeutic modality for the treatment of incurable diseases. Despite intense research, the advent to clinical utility remains compromised by numerous biological barriers, hence, there is a need for sophisticated delivery vehicles. In this aspect, lipid nanoparticles (LNPs) are the most advanced platform among nonviral vectors for gene delivery. In this review, we critically review the literature and the reasons for ineffective delivery beyond the liver. We discuss the toxicity issues associated with permanently charged cationic lipids and then turn our attention to next-generation ionizable cationic lipids. These lipids exhibit reduced toxicity and immunogenicity and undergo ionization under the acidic environment of the endosome to release the encapsulated payload to their site of action in the cytosol. Finally, we summarize recent achievements in therapeutic nucleic acid delivery and report on the current status of clinical trials using LNP and the obstacles to clinical translation.
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...
Publication - Abstract
Aug 18, 2020
Nucleic Acids Research
In this paper Alnylam Pharmaceuticals, developer of RNAi therapeutics ONPATTRO® and GIVLAARI®, investigates the biological origins of the extended duration of N-acetylgalactosamine silencing RNA (GalNAc-siRNA) activity observed in vivo.