Dendrimer-Mediated Cell Transfection in Vitro

In recent years, Starburst� PAMAM dendrimers, a class of polyamidoamine polymers, have become an interesting alternative vector for nonviral delivery of DNA in vitro and in vivo (1 -6 ). These nanoscopic polymers, characterized by regular dendritic branching, radial symmetry, and uniform size ranging from 4–11 nm, have excellent water solubility and biocompatibility in a broad range of concentrations. Nonmodified dendrimers have a high density of positively charged primary amino groups on the surface, which is essential for their interaction with counter-charged nucleic acids. Positively charged dendrimers bind DNA through electrostatic interactions with negatively charged phosphates on the DNA molecule (1 ). The consistent and predictable formation of dendrimer-DNA complexes allows for the design of efficient DNA transfections into variety of eukaryotic cell lines and primary cells in vitro (1 ,2 ,4 ,5 ,7 ). The positively charged dendrimer-DNA complexes facilitate transfer of DNA into a cell primarily through endocytosis. DNA in a complexed form is protected from nuclease activity while the majority of the DNA template remains transcriptionaly active (8 ). The well-designed dendrimer-based transfection is characterized by the lack or minimal cytotoxicity, high transfection efficiency, and stability of complexed plasmid DNA and oligonucleotides (8 ,9 ). PAMAM dendrimers can be used for gene delivery in vivo and ex vivo (6 ,10 -12 ).