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Controlling wireframe DNA origami nuclease degradation with minor groove binders

View ORCID ProfileEike-Christian Wamhoff, Hellen Huang, Benjamin J. Read, Eric Ginsburg, William R. Schief, Nicholas Farrell, Darrell J. Irvine, View ORCID ProfileMark Bathe
doi: https://doi.org/10.1101/2020.05.24.110783
Eike-Christian Wamhoff
1Massachusetts Institute of Technology, Department of Biological Engineering, Cambridge, MA 02139, United States
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  • ORCID record for Eike-Christian Wamhoff
Hellen Huang
1Massachusetts Institute of Technology, Department of Biological Engineering, Cambridge, MA 02139, United States
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Benjamin J. Read
2Massachusetts Institute of Technology, Koch Institute for Integrative Cancer Research, Cambridge, MA 02139, United States
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Eric Ginsburg
3Virginia Commonwealth University, Department of Chemistry, Richmond, VA 23284-2006, United States
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William R. Schief
4The Scripps Research Institute, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, United States
5The Scripps Research Institute, International AIDS Vaccine Initiative Neutralizing Antibody Center, La Jolla, CA 92037, United States
6The Scripps Research Institute Department of Immunology and Microbial Science, La Jolla, CA 92037 United States
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Nicholas Farrell
3Virginia Commonwealth University, Department of Chemistry, Richmond, VA 23284-2006, United States
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Darrell J. Irvine
1Massachusetts Institute of Technology, Department of Biological Engineering, Cambridge, MA 02139, United States
2Massachusetts Institute of Technology, Koch Institute for Integrative Cancer Research, Cambridge, MA 02139, United States
7Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139 United States
8Massachusetts Institute of Technology, Department of Materials Science and Engineering, Cambridge, MA 02139, United States
9Howard Hughes Medical Institute, Chevy Chase, MD 20815, United States
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Mark Bathe
1Massachusetts Institute of Technology, Department of Biological Engineering, Cambridge, MA 02139, United States
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  • ORCID record for Mark Bathe
  • For correspondence: mark.bathe@mit.edu
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Abstract

Virus-like DNA nanoparticles have emerged as promising vaccine and gene delivery platforms due to their programmable nature that offers independent control over size, shape, and functionalization. However, as biodegradable materials, their utility for specific therapeutic indications depends on their structural integrity during biodistribution to efficiently target cells, tissues, or organs. Here, we explore reversible minor groove binders to control the degradation half-lives of wireframe DNA origami. Bare, two-helix DNA nanoparticles were found to be stable under typical cell culture conditions in presence of bovine serum, yet they remain susceptible to endonucleases, specifically DNAse I. Moreover, they degrade rapidly in mouse serum, suggesting species-specific degradation. Blocking minor groove accessibility with diamidines resulted in substantial protection against endonucleases, specifically DNAse-I. This strategy was found to be compatible with both varying wireframe DNA origami architectures and functionalization with protein antigens. Our stabilization strategy offers distinct physicochemical properties compared with established cationic polymer-based methods, with synergistic therapeutic potential for minor groove binder delivery for infectious diseases and cancer.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted May 27, 2020.
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Controlling wireframe DNA origami nuclease degradation with minor groove binders
Eike-Christian Wamhoff, Hellen Huang, Benjamin J. Read, Eric Ginsburg, William R. Schief, Nicholas Farrell, Darrell J. Irvine, Mark Bathe
bioRxiv 2020.05.24.110783; doi: https://doi.org/10.1101/2020.05.24.110783
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Controlling wireframe DNA origami nuclease degradation with minor groove binders
Eike-Christian Wamhoff, Hellen Huang, Benjamin J. Read, Eric Ginsburg, William R. Schief, Nicholas Farrell, Darrell J. Irvine, Mark Bathe
bioRxiv 2020.05.24.110783; doi: https://doi.org/10.1101/2020.05.24.110783

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