Enhanced Loading of Functional miRNA Cargo via pH Gradient Modification of Extracellular Vesicles.

ABSTRACT: Based on their identification as physiological nucleic acid carriers in humans and other organisms, extracellular vesicles (EVs) have been explored as therapeutic delivery vehicles for DNA, RNA, and other cargo. However, efficient loading and functional delivery of nucleic acids remain a challenge, largely because of potential sources of degradation and aggregation. Here, we report that protonation of EVs to generate a pH gradient across EV membranes can be utilized to enhance vesicle loading of nucleic acid cargo, specifically microRNA (miRNA), small interfering RNA (siRNA), and single-stranded DNA (ssDNA). The loading process did not impair cellular uptake of EVs, nor did it promote any significant EV-induced toxicity response in mice. Cargo functionality was verified by loading HEK293T

SUBMITTER: Jeyaram A 

PROVIDER: S-EPMC7054713 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature