Delivery of genome editing tools: A promising strategy for HPV-related cervical malignancy therapy

ABSTRACT

Introduction

Persistent high-risk human papillomavirus infection is the main cause of various types of cancer especially cervical cancer. The E6 and E7 oncoproteins of HPV play critical roles in promoting carcinogenesis and cancer cell growth. As a result, E6 and E7 oncogenes are considered as promising therapeutic targets for cervical cancer. Recently, the development of genome-editing technologies including transcription activator-like effector nucleases (TALEN), meganucleases (MNs), zinc finger nucleases (ZFN), and more importantly clustered regularly interspaced short palindromic repeat-CRISPR-associated protein (CRISPR-Cas) has sparked a revolution in the cervical cancer-targeted therapy. However, due to immunogenicity, off-target effect, renal clearance, guide RNA (gRNA) nuclease degradation, and difficult direct transportation into the cytoplasm and nucleus, the safe and effective delivery is considered as the Achilles’ heel of this robust strategy.

Areas covered

In this review, we discuss cutting-edge available strategies for in vivo delivery of genome-editing technologies for HPV-induced cervical cancer therapy. Moreover, the combination of genome-editing tools and other therapies has been fully discussed.

Expert opinion

The combination of nanoparticle-based delivery systems and genome-editing tools is a promising powerful strategy for cervical cancer therapy. The most significant limitations of this strategy that need to be focused on are low efficiency and off-target events.

KEYWORDS:

• Drug delivery systems
• nanoparticles
• cervical cancer
• genome-editing tools
• viral vectors

Article highlights

• Recently, the emergence of genome-editing technologies including ZFN, TALEN, and CRISPR-Cas9 systems, has sparked a revolution in cervical cancer-targeted therapy.

• Delivery is one of the biggest challenges in genome-editing therapeutic development.

• Numerous novel viral and non-viral delivery systems have been developed.

• Cas9 may be delivered to cells in DNA, mRNA, or protein format, and each mode has unique advantages, disadvantages, and delivery requirements.

• The combination of nanocarrier systems, anti-cancer drugs, imaging agents, and CRISPR/Cas9 systems can offer a unique opportunity for the development of future cervical cancer treatment strategy.

This box summarizes the key points contained in the article.

Acknowledgments

The authors acknowledge Shahid Beheshti of the University of Medical Sciences for their support.

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 paper was not funded.