Nucleic Acids Meet Nanotechnology – A Tale of Two Approaches

The development of efficient, non-toxic materials for the intracellular delivery of nucleic acid is an important and difficult challenge in biotechnology research. This presentation focuses on two fundamentally different approaches that enable nucleic acid transport to cells. The first approach focuses on the development of cationic shell-crosslinked knedel-like nanoparticles as gene carriers. These polymer micelle-based structures are highly effective in the delivery and endosomal escape of nucleic acids in mammalian cells. The second approach exploits the cell-entry capability of spherical nucleic acids, which are nanostructures having oligonucleotides densely packed on gold nanoparticle surfaces. We show that hollow spherical nucleic acids can be synthesized using a novel gold nanoparticle-catalyzed reaction, and demonstrate that these nucleic acids can enter cells and knock down genes targets without the need of a transfection agent.