Molecular DNA dendron vaccines.

A foundational principle of rational vaccinology is that vaccine structure plays a critical role in determining therapeutic efficacy, but in order to establish fundamental, effective, and translatable vaccine design parameters, a highly modular and well-defined platform is required. Herein, we report a DNA dendron vaccine, a molecular nanostructure that consists of an adjuvant DNA strand that splits into multiple DNA branches with a varied number of conjugated peptide antigens that is capable of dendritic cell uptake, immune activation, and potent cancer killing. We leveraged the well-defined architecture and chemical modularity of the DNA dendron to study structure-function relationships that dictate molecular vaccine efficacy, particularly regarding the delivery of immune-activating DNA sequences and antigenic peptides on a single chemical construct.

Symmetry-Breaking Dendrimer Synthons in Colloidal Crystal Engineering with DNA.

Breaking symmetry in colloidal crystals is challenging due to the inherent chemical and structural isotropy of many nanoscale building blocks. If a non-particle component could be used to anisotropically encode such building blocks with orthogonal recognition properties, one could expand the scope of structural and compositional possibilities of colloidal crystals beyond what is thus far possible with purely particle-based systems. Herein, we report the synthesis and characterization of novel DNA dendrimers that function as symmetry-breaking synthons, capable of programming anisotropic and orthogonal interactions within colloidal crystals.

Spherical nucleic acids as an infectious disease vaccine platform.

SignificanceUsing SARS-CoV-2 as a relevant case study for infectious disease, we investigate the structure-function relationships that dictate antiviral spherical nucleic acid (SNA) vaccine efficacy. We show that the SNA architecture can be rapidly employed to target COVID-19 through incorporation of the receptor-binding domain, and that the resulting vaccine potently activates human cells in vitro and mice in vivo. Furthermore, when challenged with a lethal viral infection, only mice treated with the SNA vaccine survived.

Nanoparticle Superlattices through Template-Encoded DNA Dendrimers.

The chemical interactions that lead to the emergence of hierarchical structures are often highly complex and difficult to program. Herein, the synthesis of a series of superlattices based upon 30 different structurally reconfigurable DNA dendrimers is reported, each of which presents a well-defined number of single-stranded oligonucleotides (i.e.

A General DNA-Gated Hydrogel Strategy for Selective Transport of Chemical and Biological Cargos.

The selective transport of molecular cargo is critical in many biological and chemical/materials processes and applications. Although nature has evolved highly efficient biological transport systems, synthetic transport systems are often limited by the challenges associated with fine-tuning interactions between cargo and synthetic or natural transport barriers. Herein, deliberately designed DNA-DNA interactions are explored as a new modality for selective DNA-modified cargo transport through DNA-grafted hydrogel supports.