Nuclease resistance of DNA nanostructures

Abstract

DNA nanotechnology has progressed from proof-of-concept demonstrations of structural design towards application-oriented research. As a natural material with excellent self-assembling properties, DNA is an indomitable choice for various biological applications, including biosensing, cell modulation, bioimaging and drug delivery. However, a major impediment to the use of DNA nanostructures in biological applications is their susceptibility to attack by nucleases present in the physiological environment. Although several DNA nanostructures show enhanced resistance to nuclease attack compared with duplexes and plasmid DNA, this may be inadequate for practical application. Recently, several strategies have been developed to increase the nuclease resistance of DNA nanostructures while retaining their functions, and the stability of various DNA nanostructures has been studied in biological fluids, such as serum, urine and cell lysates. This Review discusses the approaches used to modulate nuclease resistance in DNA nanostructures and provides an overview of the techniques employed to evaluate resistance to degradation and quantify stability.

A mini DNA–RNA hybrid origami nanobrick

“…DNA nanostructures have shown remarkable resistance to the digestion by nucleases because of their compact structure and assembly. 17 While a majority of DNA nanostructures have been tested against DNA nucleases such as DNase I, [18][19][20] the nuclease resistance of DNA-RNA hybrid structures is less studied. We tested the stability of the mini origami nanobricks against ribonuclease H (RNase H), an enzyme that digests the RNA strand in the DNA-RNA hybrid duplex.…”

Facile Construction of a Solely-DNA-Based System for Targeted Delivery of Nucleic Acids

“…As shown in Figure 1, the system was built upon a cyclic single-stranded DNA and prepared by stepwise self-assembly. As was reported, capping the open ends of DNA strands could effectively increase their resistance to enzymatic degradation and enhance their biological stability [19,20]. In our design, the two open ends were capped simultaneously by cyclization.…”

“…As was reported, capping the open ends of DNA strands could effectively increase their resistance to enzymatic degradation and enhance their biological stability [ 19 , 20 ]. In our design, the two open ends were capped simultaneously by cyclization.…”

Hybrid Nanoassemblies from Viruses and DNA Nanostructures

“…Most of the exciting opportunities in virus-DNA hybrids research are still unexplored, and several challenges concerning optimization for physiological conditions remain to be solved, especially in case of DNA nanostructures [61,62]. The most prominent of these are stability at low-cation conditions, resistance against nucleases, low pharmacokinetic availability, low cell uptake, possible inflammatory response and accurate loading and release of drug molecules [23,24,46,52,[61][62][63][64][65][66][67][68][69][70][71]. Outstanding issues in virus-based nanocarriers are related to unknown adverse effects caused by the adaptive immunity against the viral proteins [72].…”