Nanotechnology-enabled gene delivery for cancer and other genetic diseases

ABSTRACT

Introduction

Despite gene therapy is ideal for genetic abnormality-related diseases, the easy degradation, poor targeting, and inefficiency in entering targeted cells are plaguing the effective delivery of gene therapy. Viral and non-viral vectors have been used for delivering gene therapeutics in vivo by safeguarding nucleic acid agents to target cells and to reach the specific intracellular location. A variety of nanotechnology-enabled safe and efficient systems have been successfully developed to improve the targeting ability for effective therapeutic delivery of genetic drugs.

Areas covered

In this review, we outline the multiple biological barriers associated with gene delivery process, and highlight recent advances to gene therapy strategy in vivo, including gene correction, gene silencing, gene activation and genome editing. We point out current developments and challenges exist of non-viral and viral vector systems in association with chemical and physical gene delivery technologies and their potential for the future.

Expert opinion

This review focuses on the opportunities and challenges to various gene therapy strategy, with specific emphasis on overcoming the challenges through the development of biocompatibility and smart gene vectors for potential clinical application.

KEYWORDS:

• Gene therapy
• nanotechnology
• drug delivery system
• non-viral vectors
• viral vectors

Article highlights

• Outline the multiple biological barriers associated with gene delivery process, point out several challenges exist in the clinical settings and provide an overview of the most impressive progresses made so far to overcome such challenges in recent years.

• Nucleic acid agents have been proven as promising therapeutics for treating genetic abnormality-related diseases owing to their high specificity for pathogenic targets, relatively low dose requirement for therapeutic effect, and the simplicity of the drug development process.

• While gene therapy is highly effective for cancer and other diseases, there still exists safety and efficiency issues regarding gene transfer and delivery systems.

• Gene transfer systems are the key for efficient, target-specific, and reliable gene therapy with high purity, stability, and integrity.

• Viral vectors are the preferred transfer systems. Modified viral vectors are often chosen for gene therapy because of their high delivery efficiency and sustained gene expression time. However, prominent safety concerns are haunting their gene delivery applications.

• Non-viral gene delivery systems step forward as alternative platforms to solve the functionality and safety challenges.

• Small nucleic acid drugs are one of the rapidly expanding gene therapies. We summarize the approved nucleic acid drugs by the FDA or EMA these years, which are becoming the leader in the clinical research and development for gene therapeutics.

• The advent and application of nanotechnology significantly improves the delivery efficiency of gene correction, silencing, activation and editing, as well as addresses the nonspecific off-target side effects plaguing other gene delivery systems.

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 or other relationships to disclose.

Additional information

Funding

This work was supported in part by a Startup Fund from the R. Ken Coit College of Pharmacy at The University of Arizona and a PhRMA Foundation Research Starter Grant in Drug Delivery, and by National Institutes of Health (NIH) grants (R35GM147002 and R01CA272487).