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Synthesis of DNA Origami Scaffolds: Current and Emerging Strategies

Volgenau School of Engineering, Department of Bioengineering, George Mason University, Fairfax, VA 22030, USA
Institute for Advanced Biomedical Research, George Mason University, Manassas, VA 20110, USA
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Kirill A. Afonin
Molecules 2020, 25(15), 3386;
Received: 1 July 2020 / Revised: 23 July 2020 / Accepted: 24 July 2020 / Published: 26 July 2020
(This article belongs to the Special Issue Nucleic Acid Nanobiology for Drug Delivery and Immunotherapy)
DNA origami nanocarriers have emerged as a promising tool for many biomedical applications, such as biosensing, targeted drug delivery, and cancer immunotherapy. These highly programmable nanoarchitectures are assembled into any shape or size with nanoscale precision by folding a single-stranded DNA scaffold with short complementary oligonucleotides. The standard scaffold strand used to fold DNA origami nanocarriers is usually the M13mp18 bacteriophage’s circular single-stranded DNA genome with limited design flexibility in terms of the sequence and size of the final objects. However, with the recent progress in automated DNA origami design—allowing for increasing structural complexity—and the growing number of applications, the need for scalable methods to produce custom scaffolds has become crucial to overcome the limitations of traditional methods for scaffold production. Improved scaffold synthesis strategies will help to broaden the use of DNA origami for more biomedical applications. To this end, several techniques have been developed in recent years for the scalable synthesis of single stranded DNA scaffolds with custom lengths and sequences. This review focuses on these methods and the progress that has been made to address the challenges confronting custom scaffold production for large-scale DNA origami assembly. View Full-Text
Keywords: single-stranded DNA; DNA scaffolds; DNA origami; nucleic acid nanoparticles; DNA nanotechnology; DNA Synthesis; DNA amplification single-stranded DNA; DNA scaffolds; DNA origami; nucleic acid nanoparticles; DNA nanotechnology; DNA Synthesis; DNA amplification
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Bush, J.; Singh, S.; Vargas, M.; Oktay, E.; Hu, C.-H.; Veneziano, R. Synthesis of DNA Origami Scaffolds: Current and Emerging Strategies. Molecules 2020, 25, 3386.

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