Stabilizing circulating polyplexes through systematic modification of PEGylated polyacridine peptides in vivo

Chapter 1 presents a review of the current literature on non-viral gene delivery with special emphasis on peptide gene delivery carriers and the use of acridine. Barriers to systemically-administered non-viral gene delivery and remedies to overcome them individually will be discussed, and two physical methods of particular importance in examining circulating polyplexes (DNA and peptide carrier) in vivo, hydrodynamic dosing and hydrodynamic stimulation, will also be addressed. It is suggested herein that development of a gene delivery carrier requires careful tuning of parameters that influence polyplex attributes and needs to be conducted in vivo to ensure relevant optimizations are made. Introduction Successful gene delivery therapeutics would greatly enhance the current arsenal of modern medicine against diseases stemming from gene overexpression or deficiency. Efforts to accomplish successful and efficient gene delivery are divided into two categories – viral and non-viral. Viral gene therapy has seen greater success in efficacious, in vivo protein expression owing to the evolutionary advantage of viruses equipped to handle the many challenges presented by gene delivery in mammals. While engineered viruses are the most logical choice in accomplishing gene therapy at an initial glance, the use of viruses is hindered by issues of cost of production, irreproducibility, and limits in gene size [1]. These issues are overshadowed by the even greater problem of cytotoxicity and immunogenicity, which has already proven deadly in a clinical trial [13]. Non-viral approaches are under investigation as a means to circumvent problems facing viral gene therapy but face the hurdles to accomplishing in vivo gene delivery already overcome by viruses.