Work

Exceptional Nuclease Resistance of Paranemic Crossover (PX) DNA and Crossover-Dependent Biostability of DNA Motifs

Year: 2020

Type: article

Abstract: Inherent nanometer-sized features and molecular recognition properties make DNA a useful material in constructing nanoscale objects, with alluring applications in biosensing and drug delivery. However, DNA can be easily degraded by nucleases present in biological fluids, posing a considerable roadblock to realizing the full potential of DNA nanotechnology for biomedical applications. Here we investigated the nuclease resistance and biostability of the multi-stranded motif called paranemic crossover (PX) DNA and discovered a remarkable and previously unreported resistance to nucleases. We show that PX DNA has more than an order of magnitude increased resistance to degradation by DNase I, serum, and urine compared to double stranded DNA. We further demonstrate that the degradation resistance decreases monotonically as DNA crossovers are removed from the structure, suggesting that frequent DNA crossovers disrupt either the binding or catalysis of nucleases or both. Further, we show using mouse and human cell lines that PX DNA does not affect cell proliferation or interfere with biological processes such as myogenesis. These results have important implications for building DNA nanostructures with enhanced biostability, either by adopting PX-based architectures or by carefully engineering crossovers. We contend that such crossover-dependent nuclease resistance could potentially be used to add “tunable biostability” to the many features of DNA nanotechnology.

Source: Journal of the American Chemical Society

DOI: 10.1021/jacs.0c02211

Authors: Arun Richard Chandrasekaran, Javier Vilcapoma, Paromita Dey, Siu Wah Wong-Deyrup, Bijan K. Dey, Ken Halvorsen

Institutions: University at Albany, State University of New York, State University of New York

Language: English

Topic: Advanced biosensing and bioanalysis techniques

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: American Heart Association, National Institutes of Health, National Institute of General Medical Sciences, National Institute of Arthritis and Musculoskeletal and Skin Diseases

Awards: Dysregulation of miR-133a-5p/HMGA2 axis causes skeletal and cardiac muscle degeneration by impairing autophagy in DMD, Dynamic m6A mRNA modification regulates skeletal muscle function in Duchenne Muscular Dystrophy, Manipulating nucleic acids: applications in RNA biosensing, single-molecule analysis, and DNA nanotechnology