Sprecher
Beschreibung
mRNA vaccines rely on carriers to protect the payload and deliver it into cells. Lipid nanoparticles achieve this through encapsulation but leave the mRNA’s structure untouched. Yet structure matters: the shape of a molecule can affect its uptake, translation, and immunogenicity.
We present a strategy where mRNA acts as both message and material. By hybridizing antigen-encoding mRNA with short complementary DNA strands, we fold it into defined mRNA–DNA origami. These assemblies mimic viral geometry, protect the mRNA backbone, and create a compact, programmable format.
To further improve delivery, we coated the folded mRNA with Cowpea Chlorotic Mottle Virus (CCMV) capsid proteins. These proteins self-assemble around nucleic acids, forming virus-like shells. The coating enhanced resistance to nucleases.
We tested these constructs in antigen-presenting cells, comparing them to linear mRNA. Dendritic cells translated the folded mRNA and presented the encoded epitope on MHC I. Folding required careful design to keep the 5′ cap and coding region accessible for translation.
By engineering shape as well as sequence, this platform creates new possibilities for precise and modular cancer vaccines, designed from the molecule up.
