Design strategies for programmable oligonucleotide nanotherapeutics

[Display omitted] •Design principles and strategies for pure and hybrid DNA nanostructures were reviewed.•The application of DNA as nanocarrier surface and matrix modifier was summarized.•The applications of DNA aptamers as nanotherapeutic targeting agents were compiled.•The uses of DNA nanostructures as a drug and gene delivery system were discussed.•Limitations and future perspectives of oligonucleotide nanotherapeutics were addressed. DNA nanostructures have emerged as promising novel drug and gene delivery systems. Sophisticated programmable hybrid DNA nanotherapeutics have also been used for controlled and targeted drug and gene delivery. There are also numerous reports of utilizing DNA aptamers as nanomaterials targeting moieties. However, the body of literature on these DNA-based nanotherapeutics is fragmented and is not systematically reviewed. The purpose of this review is to systematically summarize the design strategy for various oligonucleotide-based programmable nanotherapeutics that are responsive to biomolecules. A systematic review on how to design different programmable nanotherapeutics using oligonucleotides as building blocks or as surface and matrix modifiers for controlled and targeted delivery of various therapeutic agents in presented.