Oligolysine-based coating protects DNA nanostructures from low-salt denaturation and nuclease degradation

Nandhini Ponnuswamy, Maartje M. C. Bastings, Bhavik Nathwani, Ju Hee Ryu, Leo Y. T. Chou, Mathias Vinther, Weiwei Aileen Li, Frances M. Anastassacos, David J. Mooney and William M. Shih ()
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Nandhini Ponnuswamy: Dana-Farber Cancer Institute
Maartje M. C. Bastings: Dana-Farber Cancer Institute
Bhavik Nathwani: Dana-Farber Cancer Institute
Ju Hee Ryu: Dana-Farber Cancer Institute
Leo Y. T. Chou: Dana-Farber Cancer Institute
Mathias Vinther: Centre for DNA Nanotechnology, Interdisciplinary Nanoscience Center, iNANO, Aarhus University, Gustav Wieds Vej 14
Weiwei Aileen Li: Wyss Institute for Biologically Inspired Engineering at Harvard
Frances M. Anastassacos: Dana-Farber Cancer Institute
David J. Mooney: Wyss Institute for Biologically Inspired Engineering at Harvard
William M. Shih: Dana-Farber Cancer Institute

Nature Communications, 2017, vol. 8, issue 1, 1-9

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/ncomms15654

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