Dendrimers in Gene Delivery

Abstract

Delivery of nucleic acids to target cells can be achieved by both viral and nonviral delivery systems. Both of these methods have distinct advantages and disadvantages. In contrast to viral vectors, the nonviral ones provide the advantage of safety and flexibility. The disadvantage of nonviral carriers is their low efficiency. Inherent properties of dendritic nanoscale devices provide an ideal tool for development of synthetic (nonviral) carriers for delivery of nucleic acids. Among these properties, the defined architecture, high ratio of surface groups to molecular volume, and difference of hydropathic properties of interior and exterior are the most important for drug and gene delivery. Dendrimeric structures have been suggested to be used in gene therapy as potent carriers capable to, sometimes specifically, deliver DNA or RNA into the cells. Dendrimers are able to form complexes with many types of nucleic acids, such as plasmid DNA, antisense oligonucleotides, and RNA. Due to their defined architecture and a high ratio of multivalent surface moieties to molecular volume, they have become very important for the development of synthetic vectors for nucleic acid delivery. Indeed, dendrimer-based transfection agents have become routine tools for many molecular and cell biologists but the therapeutic delivery of nucleic acids complexed with dendrimer should be further investigated. The cationic dendrimers interact with the anionic backbone of nucleic acids mainly electrostatically. Complexed DNA is protected against degradation and the net positive charge of the dendrimer nucleic acid complex determines the transfection efficiency. However, highly cationic complexes are cytotoxic. Their properties can be tuned by many factors such as concentration of dendrimer amines and nucleic acid phosphates, salt concentration, stoichiometry, bulk solvent properties like pH, buffer strength, etc. For a development of dendriplex complexes with nucleic acids which can be used in gene therapy or, in general, as transfection reagents, knowledge of their transfection efficiencies and cytotoxicities is crucial.