Promising RNA-based cancer gene therapy using extracellular vesicles for drug delivery

ABSTRACT

Introduction

RNA-based cancer gene therapy shows potential in cancer treatment. However, the safe and efficient transfer of therapeutic RNA to target cells has always been a challenge. The ideal drug delivery system should be effective with low immunogenicity and toxicity. Besides, a high specificity of drug delivery is necessary to improve efficacy and avoid the side effects associated with tumor heterogeneity. As endogenous RNA vehicles, extracellular vesicles (EVs) have shown their advantages and potential as drug delivery systems in gene therapy.

Areas covered

We summarize the performance of EVs as a drug delivery system in RNA-based cancer gene therapy and discuss the advantages, limitations, and potentials of this translational medicine. In addition, we compare the characteristics and differences of current drug delivery systems and expound the principles of selecting a drug delivery system suitable for cancer gene therapy.

Expert opinion

EVs are highly biocompatible membrane structures with low cytotoxicity which provide a new choice for drug delivery in RNA-based cancer gene therapy. The specificity of engineered EVs and artificial EV-mimetics can be improved through peptide or polymer decoration. However, apart from therapeutic RNA, EVs naturally carry many molecules. This may lead to unpredictable effects and thus should be applied with caution.

KEYWORDS:

• Extracellular vesicles
• nanoparticles
• RNA vaccine
• RNA interference
• gene therapy
• RNA therapeutics

Article Highlights

• Extracellular vesicles (EVs) are highly biocompatible drug delivery systems with low cytotoxicity. These nano-sized membrane structures can cross biological barriers.

• EVs provide a promising tool for transferring therapeutic RNA in RNA-based cancer gene therapy, such as RNA interference and RNA vaccines.

• Some problems are still unresolved in therapeutic RNA delivery. The source, safety, and side effects of EVs are the main challenges in clinical applications.

This box summarizes key points contained in the article.

Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper is not funded.