Our idea was to design a novel structure using DNA or RNA and preferably with a cool function. We were inspired by the DNA box created here at Aarhus University. The box has a controllable lid and has been proposed as a nanocarrier that is able to release a drug in response to a signal. We got the idea of designing a carrier that in itself could be the drug. Since we wanted to work with nucleic acids, our idea was to create a structure using double-stranded RNA, which could be cleaved into small interfering RNAs (siRNAs). We decided to base the structure on the scaffolded origami principles known from DNA, because of the ease in using a one-pot self-assembly process and because the origami method ensures an efficient self-assembly.
We designed a structure in the shape of an octahedron with one RNA scaffold running through the entire structure. The octahedron was expected to be a rather rigid structure that maybe also could improve the stability of the RNA. The scaffold is folded in the octahedron shape by designing short oligonucleotides called staple strands, which base pair with specific domains on the scaffold. By transcribing the scaffold from a gene of interest, the idea was that the edges of the structure could be cleaved by the Dicer enzyme, thus creating more than one siRNA against the same gene hopefully resulting in a more effective knockdown. By introducing an opening mechanism in the structure (in the same way as in the DNA box) we envisioned the possibility of a responsive release of siRNA.
- Design and produce a structure of nucleic acids, with the prospect of the structure itself being part of a drug
- Verify that the scaffolded origami technique is transferable to RNA
- Verify the assembly of the structure