Extracellular vesicles for nucleic acid delivery: progress and prospects for safe RNA-based gene therapy

Abstract

Nucleic acid-based drugs offer a potentially effective tool for treatment of a variety of diseases, including cancer, cardiovascular diseases, neurological disorders and infectious diseases. However, clinical applications are hindered by instability of RNA molecules in the circulation and lack of efficient vectors that can deliver RNAs to target tissues and into diseased target cells. Synthetic polymer and lipids as well as virus-based vectors are among the most widely explored vehicles for RNA delivery, but clinical progress has been limited as a result of issues related to toxicity, immunogenicity and low efficiency. Most recently, the discovery that extracellular vesicles (EVs) are endogenous RNA carriers, which may display better biocompatibility and higher delivery efficiency as compared with the synthetic systems, has provided a ray of hope in coping with the delivery dilemma, and EV-based gene therapy has already sparked general interest both in academia and industry. In this review, the current knowledge on EV biology and their role in cell-cell communication will be summarized. Promises of EVs as drug carriers and recent technologies on tailoring EVs' biological attributes will be included, and preclinical studies in which EVs have shown promise for therapeutic RNA delivery will be discussed.

Manufacturing of Human Extracellular Vesicle-Based Therapeutics for Clinical Use

“…It can be envisaged that EVs or VSFs of unmanipulated or engineered human cells represent the therapeutically active substance of these biologic drugs [9,10,11,12,13,14,15,16,17,18,19,20,21,22,23]. To make these therapeutics available for patients in the future, it is necessary to develop scalable, reproducible and good manufacturing practice (GMP)-compliant manufacturing protocols while recognizing the benefit of regulatory frameworks.…”

PEI-Coated Fe3O4 Nanoparticles Enable Efficient Delivery of Therapeutic siRNA Targeting REST into Glioblastoma Cells

“…into a patient’s cells as a drug to treat diseases [5]. Specifically designed double-stranded siRNA could induce the specific degradation of homologous messenger RNA, leading to gene silencing [6].…”

Recent Advances in Nanoparticle-Based Cancer Drug and Gene Delivery

“…Exosomes are the most prominently studied (Jiang et al, 2017; Srivastava, Amreddy, et al, 2016; Srivastava, Babu, et al, 2016). Exosomes are nanosized (30–100nm) lipid bilayer cellular vesicles that are involved in transportation of cellular cargo.…”