Polyvalent oligonucleotide-nanoparticle conjugates possess several unique emergent properties, including enhanced cellular uptake, high antisense bioactivity, and nuclease resistance, which hypothetically originate from the dense packing and orientation of oligonucleotides on the surface of the nanoparticle. In this Communication, we describe a new class of polyvalent nucleic acid nanostructures (PNANs), which are comprised of only crosslinked and oriented nucleic acids. We demonstrate that these particles are capable of effecting high cellular uptake and gene regulation without the need of a cationic polymer co-carrier. The PNANs also exhibit cooperative binding behavior and nuclease resistance properties.