Delivery of therapeutic miRNA using polymer-based formulation.

Abstract

MicroRNAs (miRNAs) are short non-coding RNAs that play important roles in many cellular processes such as development, proliferation, differentiation, and apoptosis. For this reason, miRNAs have been proposed and investigated as biomarkers and therapeutics for various diseases such as cancer, diabetes, and cardiovascular disease. However, delivery of miRNAs and their antagomirs to target sites remains challenging because of poor cellular uptake and degradation by nucleases. Various delivery systems have been investigated for enhanced delivery of miRNAs to cells, organs, and tissues of interest, thereby enabling evaluation of their biological functions and clinical trials. In particular, non-viral, polymer-based carriers have shown advantages such as versatility of structural modifications and protection of unstable miRNA. Herein, we review properties and applications of poly (lactic-co-glycolic acid), chitosan, polyethyleneimine, and polyamidoamine dendrimers as carriers for effective delivery systems of miRNA mimic or anti-miRNAs that directly target essential miRNAs and/or their target genes. A number of miRNAs in clinical trials appear to use chemically modified miRNAs without any particular delivery system except one study with liposomal miRNA. With more accumulation of positive research results on polymeric delivery of miRNA in vitro and in vivo, we expect that polymeric delivery system will accelerate advancement of miRNA therapeutics to clinical study in the near future.