Gene‐Delivery Polymers

Abstract

Human gene therapy promises to provide unparalleled treatments for afflictions ranging from cystic fibrosis to cardiovascular disease to cancer. The development of safe and efficient methods for delivery of genetic material to specific cells within the body has been a limiting factor in implementation of this technology. Delivery methodologies have included the use of recombinant viruses and synthetic materials, especially cationic polymers. While viruses are by far the most efficient delivery vehicles currently available, polymers exhibit several properties—including very flexible chemistry, potential for biocompatibility, simplicity, and inexpensive synthesis—that make them excellent candidates for the gene delivery vehicles of the future. However, polymers are typically several orders of magnitude less efficient than viruses and are generally considered unacceptable for human gene therapy. Much work is underway to design and synthesize improved polymers for gene delivery applications. This article summarizes the important criteria for an ideal gene delivery vehicle in terms of the potential barriers that must be overcome. Further, the current state of the polymer‐mediated gene delivery field is reviewed and several new classes of polymers, specifically designed for human gene delivery, are described.

Paclitaxel-conjugated PEG and arginine-grafted bioreducible poly (disulfide amine) micelles for co-delivery of drug and gene

“…APP polyplexes reached a plateau at approximately +14 mV. The formation of polyplexes with the nanometer scale is one of the important considering factors in development of polymers for gene delivery [26, 27]. Due to the positive surface charge, the APP micelles can form polyplexes with plasmid DNA through electrostatic interaction.…”

A Degradable Polyethylenimine Derivative with Low Toxicity for Highly Efficient Gene Delivery

“…Yet it is unclear at present why these polymers are more effective than 25-kDa PEI. Potentially limiting barriers to efficient gene transfer include endocytosis, escape from endocytic vesicles into the cytoplasm, cytoplasmic motility, transport across the nuclear membrane, and unpackaging of the polyplexes ( , ). Because of the similarity of polyplexes containing 1 or 2 as compared to 25-kDa PEI, it seems unlikely that there would be significant differences in the amounts of polyplexes endocytosed, their ability to escape from endolysosomes, their cytoplasmic motility, or their transport across the nuclear membrane.…”