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
Feb 17, 2016
Journal of Bone and Mineral Research
Publication - Summary
Dec 19, 2017
Cell Reports
Inborn errors of metabolism (IEMs) can be relatively straight forward to screen for and diagnose; these disorders however, have currently very limited options for treatment. Methylmalonic acidemia (MMA), is an IEM caused by complete or partial defi...