Non‐covalent Single Transcription Factor Encapsulation Inside a DNA Cage

An elegant approach to the control of gene expression is to reversibly encapsulate the TFs in a drug-delivery cage. Within the cage, the TF cannot bind cellular DNA and is inactive; the cage can then be opened using external triggers, releasing and thus activating the TF. Molecular cages designed for encapsulation vary in size and fabrication method: fullerenes (approximately 1 nm) can encapsulate single atoms; [3] hollow metal nanoparticles [4] (approximately 100 nm) for proteins; and liposomes (100–800 nm) for drugs [5] or fluorescent molecules. [6] TF encapsulation by supramolecular nanoparticles (approximately 50 nm) for intracellular delivery has recently been reported. [7] Herein, we report a novel cage for a TF constructed using DNA. A DNA cage offers many advantages: for example, cages of dimensions similar to protein targets can be designed rationally to self-assemble in a single, rapid, and facile step. Examples of such DNA nanostructures range from polyhedra, [8] to much larger structures based on DNA origami. [9]