Design Strategy to Access siRNA-Encapsulating DNA “Nanosuitcases” That Can Conditionally Release Their Cargo
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DNA nanotechnology enables the design and assembly of DNA nanostructures with unprecedented control over their size and shape. Additionally, the programmable base-pairing alphabet of DNA allows the incorporation of responsive units within these DNA nanostructures. Here, we describe a general design strategy to construct responsive DNA prisms that can encapsulate and selectively release an encapsulated siRNA upon recognition of an oligonucleotide trigger. This prismatic DNA scaffold design is adaptable and can encapsulate oligonucleotides of any length and type. Moreover, the prism can be made to respond to an oligonucleotide trigger of interest like a messenger RNA (mRNA) or a microRNA (miRNA), thus enabling dual or synergistic therapeutic strategies. We present an overview of the design strategy used to access these DNA nanostructures, followed by the steps involved in DNA sequence generation, assembly, and validation of this construct.
KeywordsDNA nanotechnology DNA nanostructure design DNA nanostructure sequence generation Oligonucleotide drug encapsulation Conditional release
The authors would like to thank the Natural Science and Engineering Research Council of Canada, the Canada Research Chairs Program, the Fonds de recherche du Québec—Nature et technologies—the Canadian Institutes of Health, Prostate Cancer Canada, and FRQNT Center for Self-Assembled Chemical Structures for funding this work.
- 10.Koshkin AA, Singh SK, Nielsen P, Rajwanshi VK, Kumar R, Meldgaard M, Olsen CE, Wengel J (1998) LNA (Locked Nucleic Acids): synthesis of the adenine, cytosine, guanine, 5-methylcytosine, thymine and uracil bicyclonucleoside monomers, oligomerisation, and unprecedented nucleic acid recognition. Tetrahedron 54(14):3607–3630CrossRefGoogle Scholar