Recent Advances of DNA Tetrahedra for Therapeutic Delivery and Biosensing

Abstract

The chemical and self‐assembly properties of nucleic acids make them ideal for the construction of discrete structures and stimuli‐responsive devices for a diverse array of applications. Amongst the various three‐dimensional assemblies, DNA tetrahedra are of particular interest, as these structures have been shown to be readily taken up by the cell, by the process of caveolin‐mediated endocytosis, without the need for transfection agents. Moreover, these structures can be readily modified with a diverse range of pendant groups to confer greater functionality. This minireview highlights recent advances related to applications of this interesting DNA structure including the delivery of therapeutic agents ranging from small molecules to oligonucleotides in addition to its use for sensing and imaging various species within the cell.

Determining the Cytosolic Stability of Small DNA Nanostructures In Cellula

“…Further utility includes confirming the stability of structures incorporating noncanonical nuclease-resistant nucleic acids such as peptide nucleic acids (PNAs) or those with phosphorothioate internucleotide linkages. ,,,, Although this methodology only provides data on one aspect of the DNA nanostructure lifecycle within cells, its application can nevertheless help contribute to improving the design for in vivo biomedical applications. Given its non-natural structure, tetrahedron-based designs may represent an excellent place to start. ,,, …”

“…Given its non-natural structure, tetrahedron-based designs may represent an excellent place to start. 12,19,45,46 ■ ASSOCIATED CONTENT * sı Supporting Information…”

Lipid and Peptide-Oligonucleotide Conjugates for Therapeutic Purposes: From Simple Hybrids to Complex Multifunctional Assemblies

“…DNA nanostructures used as drug delivery vehicles incorporate nucleic acids drugs and target ligands within the structure itself. Among them, DNA tetrahedra [ 218 ] have been studied to show excellent results in terms of drug-loading and drug release [ 219 ]. For example, DNA tetrahedron has been functionalized with four siRNAs carrying folic acid [ 205 ], which resulted in increased therapeutic properties ( Figure 8 C).…”

Purification of Self‐Assembled DNA Tetrahedra Using Gel Electrophoresis

“…The DNA tetrahedron described here has been used often in biological applications including biosensing and drug delivery, necessitating purification of these DNA nanostructures (Copp et al., 2021; Dou et al., 2022; Xie et al., 2017; Yan et al., 2021). The DNA tetrahedron has been previously constructed and thoroughly characterized by several groups.…”

“…One of the most commonly used DNA nanostructures is the DNA tetrahedron, a class of DNA polyhedral objects that has been characterized by multiple groups and used in several applications such as biosensing, drug delivery, molecular computation, and in tracking cellular uptake of nanostructures (Copp, Pontarelli, & Wilds, 2021;Xie et al, 2017). The DNA tetrahedron discussed here contains 20 bp per double helical edge and is built from four DNA strands that are annealed together in equimolar ratios (Fig.…”