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Title: DNA origami protection and molecular interfacing through engineered sequence-defined peptoids

Abstract

DNA nanotechnology has established approaches for designing programmable and precisely controlled nanoscale architectures through specific Watson−Crick base-pairing, molecular plasticity, and intermolecular connectivity. In particular, superior control over DNA origami structures could be beneficial for biomedical applications, including biosensing, in vivo imaging, and drug and gene delivery. However, protecting DNA origami structures in complex biological fluids while preserving their structural characteristics remains a major challenge for enabling these applications. Here, we developed a class of structurally well-defined peptoids to protect DNA origamis in ionic and bioactive conditions and systematically explored the effects of peptoid architecture and sequence dependency on DNA origami stability. The applicability of this approach for drug delivery, bioimaging, and cell targeting was also demonstrated. A series of peptoids (PE1–9) with two types of architectures, termed as “brush” and “block,” were built from positively charged monomers and neutral oligo-ethyleneoxy monomers, where certain designs were found to greatly enhance the stability of DNA origami. Through experimental and molecular dynamics studies, we demonstrated the role of sequence-dependent electrostatic interactions of peptoids with the DNA backbone. We showed that octahedral DNA origamis coated with peptoid (PE2) can be used as carriers for anticancer drug and protein, where the peptoid modulated the ratemore » of drug release and prolonged protein stability against proteolytic hydrolysis. Finally, we synthesized two alkyne-modified peptoids (PE8 and PE9), conjugated with fluorophore and antibody, to make stable DNA origamis with imaging and cell-targeting capabilities. Our results demonstrate an approach toward functional and physiologically stable DNA origami for biomedical applications.« less

Authors:
; ; ORCiD logo; ; ; ; ORCiD logo; ; ORCiD logo; ORCiD logo;
Publication Date:
Sponsoring Org.:
USDOE
OSTI Identifier:
1604260
Grant/Contract Number:  
[SC0012704; AC02-05CH11231; SC0008772; KP1605010]
Resource Type:
Published Article
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
[Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Volume: 117 Journal Issue: 12]; Journal ID: ISSN 0027-8424
Publisher:
Proceedings of the National Academy of Sciences
Country of Publication:
United States
Language:
English

Citation Formats

Wang, Shih-Ting, Gray, Melissa A., Xuan, Sunting, Lin, Yiyang, Byrnes, James, Nguyen, Andy I., Todorova, Nevena, Stevens, Molly M., Bertozzi, Carolyn R., Zuckermann, Ronald N., and Gang, Oleg. DNA origami protection and molecular interfacing through engineered sequence-defined peptoids. United States: N. p., 2020. Web. doi:10.1073/pnas.1919749117.
Wang, Shih-Ting, Gray, Melissa A., Xuan, Sunting, Lin, Yiyang, Byrnes, James, Nguyen, Andy I., Todorova, Nevena, Stevens, Molly M., Bertozzi, Carolyn R., Zuckermann, Ronald N., & Gang, Oleg. DNA origami protection and molecular interfacing through engineered sequence-defined peptoids. United States. doi:10.1073/pnas.1919749117.
Wang, Shih-Ting, Gray, Melissa A., Xuan, Sunting, Lin, Yiyang, Byrnes, James, Nguyen, Andy I., Todorova, Nevena, Stevens, Molly M., Bertozzi, Carolyn R., Zuckermann, Ronald N., and Gang, Oleg. Thu . "DNA origami protection and molecular interfacing through engineered sequence-defined peptoids". United States. doi:10.1073/pnas.1919749117.
@article{osti_1604260,
title = {DNA origami protection and molecular interfacing through engineered sequence-defined peptoids},
author = {Wang, Shih-Ting and Gray, Melissa A. and Xuan, Sunting and Lin, Yiyang and Byrnes, James and Nguyen, Andy I. and Todorova, Nevena and Stevens, Molly M. and Bertozzi, Carolyn R. and Zuckermann, Ronald N. and Gang, Oleg},
abstractNote = {DNA nanotechnology has established approaches for designing programmable and precisely controlled nanoscale architectures through specific Watson−Crick base-pairing, molecular plasticity, and intermolecular connectivity. In particular, superior control over DNA origami structures could be beneficial for biomedical applications, including biosensing, in vivo imaging, and drug and gene delivery. However, protecting DNA origami structures in complex biological fluids while preserving their structural characteristics remains a major challenge for enabling these applications. Here, we developed a class of structurally well-defined peptoids to protect DNA origamis in ionic and bioactive conditions and systematically explored the effects of peptoid architecture and sequence dependency on DNA origami stability. The applicability of this approach for drug delivery, bioimaging, and cell targeting was also demonstrated. A series of peptoids (PE1–9) with two types of architectures, termed as “brush” and “block,” were built from positively charged monomers and neutral oligo-ethyleneoxy monomers, where certain designs were found to greatly enhance the stability of DNA origami. Through experimental and molecular dynamics studies, we demonstrated the role of sequence-dependent electrostatic interactions of peptoids with the DNA backbone. We showed that octahedral DNA origamis coated with peptoid (PE2) can be used as carriers for anticancer drug and protein, where the peptoid modulated the rate of drug release and prolonged protein stability against proteolytic hydrolysis. Finally, we synthesized two alkyne-modified peptoids (PE8 and PE9), conjugated with fluorophore and antibody, to make stable DNA origamis with imaging and cell-targeting capabilities. Our results demonstrate an approach toward functional and physiologically stable DNA origami for biomedical applications.},
doi = {10.1073/pnas.1919749117},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = [12],
volume = [117],
place = {United States},
year = {2020},
month = {3}
}

Journal Article:
Free Publicly Available Full Text
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DOI: 10.1073/pnas.1919749117

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Works referenced in this record:

Virus-Encapsulated DNA Origami Nanostructures for Cellular Delivery
journal, March 2014

  • Mikkilä, Joona; Eskelinen, Antti-Pekka; Niemelä, Elina H.
  • Nano Letters, Vol. 14, Issue 4
  • DOI: 10.1021/nl500677j

Addressing the Instability of DNA Nanostructures in Tissue Culture
journal, August 2014

  • Hahn, Jaeseung; Wickham, Shelley F. J.; Shih, William M.
  • ACS Nano, Vol. 8, Issue 9
  • DOI: 10.1021/nn503513p

Designer DNA Nanoarchitectures
journal, March 2009

  • Lin, Chenxiang; Liu, Yan; Yan, Hao
  • Biochemistry, Vol. 48, Issue 8, p. 1663-1674
  • DOI: 10.1021/bi802324w

Proteolytic studies of homologous peptide and N-substituted glycine peptoid oligomers
journal, November 1994


Programmable and Multifunctional DNA-Based Materials for Biomedical Applications
journal, February 2018


Peptoidic Amino- and Guanidinium-Carrier Systems: Targeted Drug Delivery into the Cell Cytosol or the Nucleus
journal, February 2008

  • Schröder, Tina; Niemeier, Nicole; Afonin, Sergii
  • Journal of Medicinal Chemistry, Vol. 51, Issue 3
  • DOI: 10.1021/jm070603m

DNA Origami as a Carrier for Circumvention of Drug Resistance
journal, August 2012

  • Jiang, Qiao; Song, Chen; Nangreave, Jeanette
  • Journal of the American Chemical Society, Vol. 134, Issue 32
  • DOI: 10.1021/ja304263n

BioXTAS RAW : improvements to a free open-source program for small-angle X-ray scattering data reduction and analysis
journal, September 2017

  • Hopkins, Jesse Bennett; Gillilan, Richard E.; Skou, Soren
  • Journal of Applied Crystallography, Vol. 50, Issue 5
  • DOI: 10.1107/S1600576717011438

Sequence-Specific Molecular Lithography on Single DNA Molecules
journal, July 2002


A general strategy for the DNA-mediated self-assembly of functional nanoparticles into heterogeneous systems
journal, October 2013

  • Zhang, Yugang; Lu, Fang; Yager, Kevin G.
  • Nature Nanotechnology, Vol. 8, Issue 11
  • DOI: 10.1038/nnano.2013.209

One-Step Formation of “Chain-Armor”-Stabilized DNA Nanostructures
journal, May 2015

  • Cassinelli, Valentina; Oberleitner, Birgit; Sobotta, Jessica
  • Angewandte Chemie International Edition, Vol. 54, Issue 27
  • DOI: 10.1002/anie.201500561

DNA-guided crystallization of colloidal nanoparticles
journal, January 2008

  • Nykypanchuk, Dmytro; Maye, Mathew M.; van der Lelie, Daniel
  • Nature, Vol. 451, Issue 7178, p. 549-552
  • DOI: 10.1038/nature06560

Cellular Immunostimulation by CpG-Sequence-Coated DNA Origami Structures
journal, November 2011

  • Schüller, Verena J.; Heidegger, Simon; Sandholzer, Nadja
  • ACS Nano, Vol. 5, Issue 12
  • DOI: 10.1021/nn203161y

Hydration Regulates Thermodynamics of G-Quadruplex Formation under Molecular Crowding Conditions
journal, June 2006

  • Miyoshi, Daisuke; Karimata, Hisae; Sugimoto, Naoki
  • Journal of the American Chemical Society, Vol. 128, Issue 24
  • DOI: 10.1021/ja061267m

Folding DNA to create nanoscale shapes and patterns
journal, March 2006


Smart Drug Delivery Nanocarriers with Self-Assembled DNA Nanostructures
journal, June 2013


Platinated DNA as Precursors to Templated Chains of Metal Nanoparticles
journal, December 2001


A Logic-Gated Nanorobot for Targeted Transport of Molecular Payloads
journal, February 2012


Intramolecular fluorescence self-quenching of fluoresceinamine
journal, March 1990

  • Munkholm, Christiane; Parkinson, Don R.; Walt, David R.
  • Journal of the American Chemical Society, Vol. 112, Issue 7
  • DOI: 10.1021/ja00163a021

Effects of Hydration, Ion Release, and Excluded Volume on the Melting of Triplex and Duplex DNA
journal, January 1999

  • Spink, Charles H.; Chaires, Jonathan B.
  • Biochemistry, Vol. 38, Issue 1
  • DOI: 10.1021/bi9820154

Organization of 'nanocrystal molecules' using DNA
journal, August 1996

  • Alivisatos, A. Paul; Johnsson, Kai P.; Peng, Xiaogang
  • Nature, Vol. 382, Issue 6592
  • DOI: 10.1038/382609a0

The design, synthesis, and evaluation of molecules that enable or enhance cellular uptake: Peptoid molecular transporters
journal, November 2000

  • Wender, P. A.; Mitchell, D. J.; Pattabiraman, K.
  • Proceedings of the National Academy of Sciences, Vol. 97, Issue 24, p. 13003-13008
  • DOI: 10.1073/pnas.97.24.13003

Oligolysine-based coating protects DNA nanostructures from low-salt denaturation and nuclease degradation
journal, May 2017

  • Ponnuswamy, Nandhini; Bastings, Maartje M. C.; Nathwani, Bhavik
  • Nature Communications, Vol. 8, Issue 1
  • DOI: 10.1038/ncomms15654

Prescribed nanoparticle cluster architectures and low-dimensional arrays built using octahedral DNA origami frames
journal, May 2015


Block Copolymer Micellization as a Protection Strategy for DNA Origami
journal, March 2017

  • Agarwal, Nayan P.; Matthies, Michael; Gür, Fatih N.
  • Angewandte Chemie International Edition, Vol. 56, Issue 20
  • DOI: 10.1002/anie.201608873

DNA rendering of polyhedral meshes at the nanoscale
journal, July 2015

  • Benson, Erik; Mohammed, Abdulmelik; Gardell, Johan
  • Nature, Vol. 523, Issue 7561
  • DOI: 10.1038/nature14586

Control of enzyme reactions by a reconfigurable DNA nanovault
journal, October 2017

  • Grossi, Guido; Dalgaard Ebbesen Jepsen, Mette; Kjems, Jørgen
  • Nature Communications, Vol. 8, Issue 1
  • DOI: 10.1038/s41467-017-01072-8

DNase I-induced DNA conformation
journal, December 1991


DNA in a material world
journal, January 2003


Universal computing by DNA origami robots in a living animal
journal, April 2014

  • Amir, Yaniv; Ben-Ishay, Eldad; Levner, Daniel
  • Nature Nanotechnology, Vol. 9, Issue 5
  • DOI: 10.1038/nnano.2014.58

A DNA-based method for rationally assembling nanoparticles into macroscopic materials
journal, August 1996

  • Mirkin, Chad A.; Letsinger, Robert L.; Mucic, Robert C.
  • Nature, Vol. 382, Issue 6592, p. 607-609
  • DOI: 10.1038/382607a0

DNA Nanocages
journal, August 2016


Recent Advances in the Synthesis of Peptoid Macrocycles
journal, February 2018

  • Webster, Alexandra M.; Cobb, Steven L.
  • Chemistry - A European Journal, Vol. 24, Issue 30
  • DOI: 10.1002/chem.201705340

Optimized DNA “Nanosuitcases” for Encapsulation and Conditional Release of siRNA
journal, October 2016

  • Bujold, Katherine E.; Hsu, John C. C.; Sleiman, Hanadi F.
  • Journal of the American Chemical Society, Vol. 138, Issue 42
  • DOI: 10.1021/jacs.6b08369

Effects of Design Choices on the Stiffness of Wireframe DNA Origami Structures
journal, August 2018

  • Benson, Erik; Mohammed, Abdulmelik; Rayneau-Kirkhope, Daniel
  • ACS Nano, Vol. 12, Issue 9
  • DOI: 10.1021/acsnano.8b04148

Atomic-level engineering and imaging of polypeptoid crystal lattices
journal, October 2019

  • Xuan, Sunting; Jiang, Xi; Spencer, Ryan K.
  • Proceedings of the National Academy of Sciences, Vol. 116, Issue 45
  • DOI: 10.1073/pnas.1909992116

Peptoid Polymers: A Highly Designable Bioinspired Material
journal, May 2013


DNA Origami as an In Vivo Drug Delivery Vehicle for Cancer Therapy
journal, June 2014


Designer nanoscale DNA assemblies programmed from the top down
journal, May 2016


Challenges and opportunities for structural DNA nanotechnology
journal, November 2011

  • Pinheiro, Andre V.; Han, Dongran; Shih, William M.
  • Nature Nanotechnology, Vol. 6, Issue 12
  • DOI: 10.1038/nnano.2011.187

Highly sensitive fluorescent detection of trypsin based on BSA-stabilized gold nanoclusters
journal, February 2012


Covalent DNA-Streptavidin Conjugates as Building Blocks for Novel Biometallic Nanostructures
journal, September 1998


Protein Coating of DNA Nanostructures for Enhanced Stability and Immunocompatibility
journal, July 2017


New Peptidomimetic Polymers for Antifouling Surfaces
journal, June 2005

  • Statz, Andrea R.; Meagher, Robert J.; Barron, Annelise E.
  • Journal of the American Chemical Society, Vol. 127, Issue 22
  • DOI: 10.1021/ja0522534

Precisely Tailored DNA Nanostructures and their Theranostic Applications
journal, June 2017


Lattice engineering through nanoparticle–DNA frameworks
journal, February 2016

  • Tian, Ye; Zhang, Yugang; Wang, Tong
  • Nature Materials, Vol. 15, Issue 6, p. 654-661
  • DOI: 10.1038/nmat4571

Nucleases: diversity of structure, function and mechanism
journal, September 2010


Cationic polymers for DNA origami coating – examining their binding efficiency and tuning the enzymatic reaction rates
journal, January 2016

  • Kiviaho, Jenny K.; Linko, Veikko; Ora, Ari
  • Nanoscale, Vol. 8, Issue 22
  • DOI: 10.1039/C5NR08355A

A combinatorial approach to the discovery of efficient cationic peptoid reagents for gene delivery
journal, February 1998

  • Murphy, J. E.; Uno, T.; Hamer, J. D.
  • Proceedings of the National Academy of Sciences, Vol. 95, Issue 4
  • DOI: 10.1073/pnas.95.4.1517

Cellular delivery of enzyme-loaded DNA origami
journal, January 2016

  • Ora, Ari; Järvihaavisto, Erika; Zhang, Hongbo
  • Chemical Communications, Vol. 52, Issue 98
  • DOI: 10.1039/C6CC08197E

Arginine-Rich Molecular Transporters for Drug Delivery:  Role of Backbone Spacing in Cellular Uptake
journal, August 2002

  • Rothbard, Jonathan B.; Kreider, Erik; VanDeusen, Christopher L.
  • Journal of Medicinal Chemistry, Vol. 45, Issue 17
  • DOI: 10.1021/jm0105676

Spatially-Interactive Biomolecular Networks Organized by Nucleic Acid Nanostructures
journal, May 2012

  • Fu, Jinglin; Liu, Minghui; Liu, Yan
  • Accounts of Chemical Research, Vol. 45, Issue 8
  • DOI: 10.1021/ar200295q

Synthesis and Characterization of Well-Defined PEGylated Polypeptoids as Protein-Resistant Polymers
journal, February 2017


SYBR Green I: Fluorescence Properties and Interaction with DNA
journal, April 2012


Precision glycocalyx editing as a strategy for cancer immunotherapy
journal, August 2016

  • Xiao, Han; Woods, Elliot C.; Vukojicic, Petar
  • Proceedings of the National Academy of Sciences, Vol. 113, Issue 37
  • DOI: 10.1073/pnas.1608069113

DNA Surface Technology: From Gene Sensors to Integrated Systems for Life and Materials Sciences
journal, December 2018

  • Schneider, Ann-Kathrin; Niemeyer, Christof M.
  • Angewandte Chemie International Edition, Vol. 57, Issue 52
  • DOI: 10.1002/anie.201811713

Stability of DNA Origami Nanostructure under Diverse Chemical Environments
journal, September 2014

  • Kim, Hyojeong; Surwade, Sumedh P.; Powell, Anna
  • Chemistry of Materials, Vol. 26, Issue 18
  • DOI: 10.1021/cm5019663

On the Stability of DNA Origami Nanostructures in Low-Magnesium Buffers
journal, June 2018

  • Kielar, Charlotte; Xin, Yang; Shen, Boxuan
  • Angewandte Chemie International Edition, Vol. 57, Issue 30
  • DOI: 10.1002/anie.201802890

Cocoon-Like Self-Degradable DNA Nanoclew for Anticancer Drug Delivery
journal, October 2014

  • Sun, Wujin; Jiang, Tianyue; Lu, Yue
  • Journal of the American Chemical Society, Vol. 136, Issue 42
  • DOI: 10.1021/ja5088024

Sequence-programmable covalent bonding of designed DNA assemblies
journal, August 2018

  • Gerling, Thomas; Kube, Massimo; Kick, Benjamin
  • Science Advances, Vol. 4, Issue 8
  • DOI: 10.1126/sciadv.aau1157

Self-assembly of DNA into nanoscale three-dimensional shapes
journal, May 2009

  • Douglas, Shawn M.; Dietz, Hendrik; Liedl, Tim
  • Nature, Vol. 459, Issue 7245
  • DOI: 10.1038/nature08016

Control of stability and structure of nucleic acids using cosolutes
journal, May 2014