Current progress of polymeric gene vectors

Abstract

After over 40 years of progress, gene therapy provides great opportunities for treating diseases from various genetic disorders, infections and cancers. The success of gene therapy largely depends on the availability of suitable gene vectors. As an attractive alternative to virus-based gene therapy, non-viral gene delivery system has been developed and investigated due to their merits including low immunogenecity, convenient operability, and large-scale manufacturability [1]. Because polycations can condense with DNA as a result of electrostatic interactions, form nanosize polyplexes, and protect DNA from degradation by DNase, cationic polymer becomes a major type of non-viral gene delivery vectors ( Figure 1) [2]. A wide range of polymeric vectors have been developed and investigated in the past decade, such as polyethylenimine (PEI)-based vectors, poly(L-lysine) (PLL)-based vectors, dendrimer-based vectors, polypeptide-based vectors, and chitosan-based vectors [3]. However, unlike viral vectors that have the ability to infect host cells and overcome cellular barriers through the course of evolution, nonviral gene vectors exhibit significantly reduced transfection efficiency as they are obstructed by various extra-and intracellular barriers, including serum proteins in blood stream, cell membrane, endosomal compartment and nuclear membrane [4].As a result, numerous studies have focused on designing polymer carriers that have smart molecular structure, present good biocompatibility, avoid both in vitro and in vivo barriers, and achieve successful delivery of genetic material [1]. To circumvent different systemic and cellular obstacles Figure 1 Three main strategies employed to package DNA [4].during gene delivery, proper functional groups were conjugated to polymeric vectors. The current modification of polymeric vectors has shown great improvements in enhancing intracellular gene transfer efficiency and attaining tumor targeted gene delivery [4]. For example, receptormediated cell uptake can quickly deliver ligand-targeted polyplexes into endosomes, membrane active compounds (lipids and peptides) can enhance the release of endocytosed materials. Moreover, nuclear localization signal peptides can enhance both the nuclear transport and expression of DNA. Here, current research progress regarding polymeric gene vectors that mainly published in Chinese magazines from 2010 was reviewed, and future trends for the polymer-based gene delivery systems would also be delineated.