A Dendrimer-Like DNA-Based Vector for DNA Delivery: A Viral and Nonviral Hybrid Approach

DNA can be used as a generic delivery vector in addition to its genetic role as a antigen expression vector. This is inspired in part by the fact that DNA molecules are true polymers. Surprisingly, DNA molecules have not been used as a delivery vector material. This is probably due to the fact that almost all DNA have only two shapes: linear or circular. This chapter details our efforts in fabricating highly branched dendrimer-like DNA (DL-DNA) that may serve as a multivalent DNA delivery vector. Just like chemical dendrimers, DL-DNA is multivalent and monodisperse. However, unlike traditional chemical dendrimers, DL-DNA is much larger (∼100 nm, generation 4) and can be designed to be nonsymmetric as well. Most importantly, DL-DNA possesses two unique properties: anisotropicity and biodegradability, making multiple, specific conjugations of viral peptides possible. Our method suggests that viral-peptide conjugated DL-DNA vectors can deliver genes into cells without any other transfection reagents. This viral-nonviral hybrid system can be further tailored to specific cells by conjugating specific ligands. We believe that such a DL-DNA-based, viral, and nonviral hybrid assembly will provide a new platform for drug delivery in general and gene delivery in particular.