Extracellular Vesicles for Therapeutic Nucleic Acid Delivery: Loading Strategies and Challenges

Abstract

Extracellular vesicles (EVs) are membrane vesicles released into the extracellular milieu by cells of various origins. They contain different biological cargoes, protecting them from degradation by environmental factors. There is an opinion that EVs have a number of advantages over synthetic carriers, creating new opportunities for drug delivery. In this review, we discuss the ability of EVs to function as carriers for therapeutic nucleic acids (tNAs), challenges associated with the use of such carriers in vivo, and various strategies for tNA loading into EVs.

Functionalized 3D Hydroxyapatite Scaffold by Fusion Peptides-Mediated Small Extracellular Vesicles of Stem Cells for Bone Tissue Regeneration

“…The connection of sEVs and peptides mainly depends on the interactions and identification between CP05 and CD63. CP05 can specifically bind to the second extracellular loop of CD63, a transmembrane protein in sEVs …”

“…The sEVs have emerged as natural drug carriers with several advantages, including low immunogenicity and prolonged circulation times in vivo. These carriers leverage the membrane proteins such as CD63, CD9, and CD81 in sEVs to achieve fusion expression . CP05 (CRHSQMTVTSRL) is a short molecular polypeptide that can specifically bind to the CD63 surface protein on sEVs .…”

Unraveling the Multifaceted Roles of Extracellular Vesicles: Insights into Biology, Pharmacology, and Pharmaceutical Applications for Drug Delivery

“…There are a few proposed mechanisms based on pH-dependent permeability for endosomal escape of cargo into the cytoplasm, where it can carry out its specific function [ 381 , 382 ]. One of the major hurdles in utilizing EVs for clinical application is the understanding of the mechanisms of EV cargo release into the cytoplasm and the poor predictability of the process across different cell types [ 381 , 383 , 384 ]. Similarly, much remains to be understood about the transmission of EVs in the blood and the crossing of the endothelial layers of blood vessels.…”

Emerging Roles of Using Small Extracellular Vesicles as an Anti-Cancer Drug

“…The introduction of nucleic acids into parent cells can allow the generation of modified sEVs containing the introduced nucleic acids. The modification process can be performed without compromising the sEV membrane integrity [ 94 ]. Liu et al transduced cells with lentivirus-miR-7-5p to produce miR-7-5p containing sEVs (exo-miR-7-5p) [ 90 ].…”