Recent advances in the development of polyethylenimine-based gene vectors for safe and efficient gene delivery

ABSTRACT

Introduction

Despite the great therapeutic potential of gene therapy for treating critical diseases, the clinical application is limited by lack of safe and effective gene delivery vectors. Nonviral gene vectors have attracted tremendous attention due to the favorable loading capacity and facile manufacture. Among them, polyethylenimine-based gene vectors (PEIs) hold great promise for highly efficient gene delivery.

Areas covered

In this review, we outline the multiple biological barriers associated with gene delivery process and point out several challenges exist in the clinical usage of PEIs. We then provide an overview of the most impressive progresses made to overcome such challenges in recent years, including modifications of PEIs (i.e. to enhance biocompatibility, specific targeting effect, and buffering capacity) and stimuli-responsive strategies (i.e. endogenous and exogenous stimuli) for safe and efficient gene delivery.

Expert opinion

Rational modification of PEIs with diverse functionalized segments or the development of stimuli-responsive PEIs is an appealing strategy to meet some requirements involved in gene delivery. Nevertheless, further optimization by combining the two strategies is needed for the maximized transfection efficiency and minimized side effects, shedding new light on the development of nonviral gene delivery for clinical application.

KEYWORDS:

• Polyethyleneimine
• gene therapy
• gene delivery
• dual-sensitive
• gene vector
• stimuli-responsive

Article highlights

• PEI-based nonviral gene vectors exhibit multiple advantages over viral vectors for gene delivery, including high loading capacity, low immunogenicity, and facile manufacture.

• The gene transfection efficiency is positively related to the molecular weight of PEI, while the cytotoxicity is negatively correlated with it.

• Modifications of PEI with some polymers or molecules that show favorable biocompatibility, specific targeting, or high buffering capacity promote the gene transfection efficiency and reduce the cytotoxicity.

• Stimuli-responsive PEI-based gene vectors can stabilize the payload gene in the systemic circulation and release the cargoes specifically and timely at the pathological target site, thus to maximize the gene transfection efficiency and minimize the side effects.

• Dual-responsive strategies facilitate a programmed sequential gene release or a faster and more precise responsiveness.

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 or other relationships to disclose.

Additional information

Funding

The authors were supported by National Science and Technology Major Project of China (2017YFA0205400), National Natural Science Foundation of China (81773669), and Graduate Cultivation Innovative Project of Jiangsu Province (KYCX17_0677).