Octahedral RNA origami for simultaneous drug delivery and gene knockdown
An RNA octahedron was designed that can be folded through scaffolded RNA origami on any RNA sequence. By designing specific recognition sites for the Dicer enzyme the structure can release up to 5 siRNAs towards the same gene resulting in effective knockdown. In addition, the structure can release drug molecules either in response to a miRNA signal or the Dicer cleavage. Here we characterise the structure of the RNA octahedron using PAGE and biophysical techniques, and the function by specific cleavage of the structure by the Dicer enzyme and gene knockdown using a dual Luciferase assay. We used a DNA/RNA hybrid to characterize opening of the structure by FRET measurements. Our project demonstrates that RNA nano-structures can be designed as multipurpose devices for both stability, drug release and using the scaffold as the active therapeutic agent.
Centreret billede af strukturen
- "Any intelligent fool can make things bigger and more complex... It takes a touch of genius - and a lot of courage to move in the opposite direction."