Overcoming Nonviral Gene Delivery Barriers: Perspective and Future

Abstract

A key end goal of gene delivery research is to develop clinically-relevant vectors that can be used to combat elusive diseases such as AIDS. Despite promising engineering strategies, efficiency and ultimately gene modulation efficacy of nonviral vectors have been hindered by numerous in vitro and in vivo barriers that have resulted in sub-viral performance. In this perspective, we concentrate on the gene delivery barriers associated with the two most common classes of nonviral vectors, cationic-based lipids and polymers. We present the existing delivery barriers and summarize current vector-specific strategies to overcome said barriers.

Non Viral Vectors in Gene Therapy- An Overview

“…Neutral polymer like polyethylene glycol (PEG) is used as surface shielding to overcome the excessive charge and to prolong the half-life. Though considered to be of low toxicity, lipoplexes become cytotoxic beyond 3:1 ratio of lipid: DNA [6,12,15,20,[23][24][25].…”

Involvement of a Rac1-Dependent Macropinocytosis Pathway in Plasmid DNA Delivery by Electrotransfection

“…[1][2][3][4][5] The treatment requires delivery of therapeutic genes into nucleus of specific cells in tissues, which must overcome several physical and biological barriers. 6 One such barrier is the plasma membrane of cell, which physically limits material exchange between intra-and extracellular environments. In addition, both DNA and plasma membrane are negatively charged, which means that the repulsive electrostatic force could hinder delivery of naked DNA into cells as well.…”

A Triple-Fluorophore-Labeled Nucleic Acid pH Nanosensor to Investigate Non-viral Gene Delivery

“…1,2 Despite extensive progress in the previous decade, many challenges in engineering successful non-viral gene delivery platforms remain. 1,3 Polymeric gene delivery in particular has made extensive progress toward increased performance through rational engineering of polymer structures as well as screening of broad libraries of polymer structures, but new quantitative bioassays are required to fully understand the mechanisms by which existing nanoparticles achieve transfection. [4][5][6][7][8][9][10][11] Barriers to successful polymeric gene delivery at the level of individual cells include cellular internalization, endosomal escape, nucleic acid unpacking, and nuclear transport.…”