Emerging Research on Gene Delivery to the Nucleus via DNA Origami

Structural DNA nanotechnology, a research field in which scientists use DNA as the primary material to make designer nanostructures, has experienced rapid growth in the past few decades. The continuous development of the field has produced a rich repository of impressive, complex nanostructures for applications in materials science, biological research, and therapeutics. The unprecedented programmability of DNA nanostructures, particularly DNA origami, combined with the biocompatibility and rich functionality of DNA molecules make them attractive candidates for building nanocarriers for cellular delivery. While the initial research toward this direction focused on the delivery of small molecule drugs and short nucleic acids, emerging efforts in the last two years have expanded to gene delivery by leveraging the capacity of DNA origami to fold gene sequences into compact structures amenable for cell delivery. Here, we review this exciting research direction and provide our perspective on the challenges and opportunities in this field.