title: Decationized polyplexes for gene delivery.
abstract: Gene therapy has received much attention in the field of drug delivery. Synthetic, nonviral gene delivery systems have gained increasing attention as vectors for gene therapy mainly due to a favorable immunogenicity profile and ease of manufacturing as compared to viral vectors. The great majority of these formulations are based on polycationic structures, due to their ability to interact with negatively charged nucleic acids to spontaneously form nanoparticles. In recent years, several polycationic systems have demonstrated high transfection in vitro. However, progress toward clinical applications has been slow, mainly because the cationic nature of these systems leads to intolerable toxicity levels, inappropriate biodistribution and unsatisfactory efficiency in vivo, particularly after systemic administration. Decationized polyplexes are a new class of gene delivery systems that have been developed as an alternative for conventional polycation-based systems. The major innovation introduced by decationized polyplexes is that these systems are based on neutral polymers, without any detrimental effect on the physicochemical stability or encapsulation ability, due to the transient presence of cationic charge and disulfide cross-links between the polymer chains by which the nucleic acids are physically entrapped in the particles. This editorial summarizes the most important features of decationized polyplexes and discusses potential implications for the development of new safe and efficient gene delivery systems.
authors.affiliation: Utrecht University, Utrecht Institute for Pharmaceutical Sciences, Department of Pharmaceutics , 3584 CG Utrecht , The Netherlands w.e.hennink@uu.nl.
authors.forename: Luís
authors.initials: L
authors.lastname: Novo
authors.forename: Enrico
authors.initials: E
authors.lastname: Mastrobattista
authors.forename: Cornelus F
authors.initials: CF
authors.lastname: van Nostrum
authors.forename: Twan
authors.initials: T
authors.lastname: Lammers
authors.forename: Wim E
authors.initials: WE
authors.lastname: Hennink
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D053758:Nanoparticles; D011108:Polymers / Q000737:chemistry*; D014018:Tissue Distribution; D014162:Transfection
chemical_list: D011108:Polymers
keywords: biocompatibility; gene delivery; nanoparticle; polymer; targeting