Ponnuswamy, Nandhini Bastings, Maartje M. C. Nathwani, Bhavik Ryu, Ju Hee Chou, Leo Y. T. Vinther, Mathias Li, Weiwei Aileen Anastassacos, Frances M. Mooney, David J. Shih, William M. 2024-01-20T01:33:19Z 2024-01-20T01:33:19Z 2021-09-01 2017-05 2041-1723 https://pubs.kist.re.kr/handle/201004/122803 DNA nanostructures have evoked great interest as potential therapeutics and diagnostics due to ease and robustness of programming their shapes, site-specific functionalizations and responsive behaviours. However, their utility in biological fluids can be compromised through denaturation induced by physiological salt concentrations and degradation mediated by nucleases. Here we demonstrate that DNA nanostructures coated by oligolysines to 0.5: 1 N:P (ratio of nitrogen in lysine to phosphorus in DNA), are stable in low salt and up to tenfold more resistant to DNase I digestion than when uncoated. Higher N: P ratios can lead to aggregation, but this can be circumvented by coating instead with an oligolysine-PEG copolymer, enabling up to a 1,000-fold protection against digestion by serum nucleases. Oligolysine-PEG-stabilized DNA nanostructures survive uptake into endosomal compartments and, in a mouse model, exhibit a modest increase in pharmacokinetic bioavailability. Thus, oligolysine-PEG is a one-step, structure-independent approach that provides low-cost and effective protection of DNA nanostructures for in vivo applications. English Nature Publishing Group Oligolysine-based coating protects DNA nanostructures from low-salt denaturation and nuclease degradation Article 10.1038/ncomms15654 1 Nature Communications, v.8 Nature Communications 8 Y scie scopus 000402395500001 2-s2.0-85019998190 Multidisciplinary Sciences Science & Technology - Other Topics Article ORIGAMI NANOSTRUCTURES INTRACELLULAR DELIVERY DENDRITIC CELLS IN-VIVO SELF NANOSCALE SHAPES STABILITY CULTURE