The aim of gene therapy is to transfer genetic material into cells to specifically alter their function by increasing or decreasing the expression of a desired gene. Following two decades of research, there are two major methods for the delivery of genetic material such as DNA or RNA into cells: viral and nonviral vectors. Though viral vectors are an efficient tool of transfection, their therapeutic use is compromised by serious safety concerns such as immunogenicity and insertional mutagenesis. Hence, nonviral vectors, which are able to form nanocarriers for nucleic acid delivery, offer a potentially attractive alternative due to their low or absent immunogenicity, possibility to be easily scaled up, and flexibility with regard to vector modification. The aim of this review is to give an overview of common nonviral, particularly polycationic-based vectors presently used in gene delivery. One major part is description and classification of polycations like i.e. polylysines, polyethylenimines, poly(β-amino ester)s, dextrans, dendrimers and others. The second part is focused on modification of polymer/DNA-complexes (polyplexes) with targeting ligands for improved gene transfer into cells, concerning uptake specificity and reduced toxicity. Short-term gene expression limits the use of cationic complexes because of enzymatic DNA degradation and inactivation. However, effective gene therapy requires controlled release and expression of the desired gene. To overcome repeated administration and large dosages, several investigations have been made to generate sustained gene delivery systems using different natural and synthetic polymeric biocompatible materials. Therefore, the focus of the last part is placed on polymeric biocompatible materials like poly (lactide-co-glycolide) with favourable biological properties: Biodegradability and biocompatibility, resulting in low immunogenity. Additionally, several slow release technologies, including nano- and microparticels as well as standard and in situ forming implants, are discussed with regard to their potential for therapeutic use.
Nanoparticles, gene delivery, polymer, controlled release, targeting
Department of Pediatrics, Ludwig- Maximilians University, Lindwurmstr. 2a, D-80337 Munich, Germany.