Abstract:
The structural characteristics of DNA, including its molecular recognition properties, its programmable synthesis and its cooperative assembly into a double helix have greatly inspired modern sciences. The last three decades have seen the rise of DNA nanotechnology as an accessible approach to design and assemble well-defined DNA nanostructures with unprecedented control. Moreover, the biocompatibility of DNA predisposes it for therapeutic applications, both as a drug and as a selective drug delivery vehicle. However, DNA-based transporters are limited by their low cellular uptake and show rapid degradation in serum. The main goal of this work was to address these shortcomings by developing strategies that will improve the biological properties of DNA nanostructures. These include 1) modulating their cellular uptake profile with synthetic insertions, 2) incorporating stimuli-responsive parts to enable the selective delivery of drugs and 3) improving the synthesis and incorporation of biologically relevant oligonucleotide modifications. Taken together, these findings have increased the access to optimized DNA nanostructures for applications at the interface with biology.