Customized Scaffolds for Direct Assembly of Functionalized DNA Origami.

Content Provider	Europe PMC
Author	Oktay, Esra Bush, Joshua Vargas, Merlyn Scarton, Dylan Valerio O’Shea, Bailey Hartman, Amber Green, Christopher M. Neyra, Kayla Gomes, Carolina M. Medintz, Igor L. Mathur, Divita Veneziano, Remi
Copyright Year	2023
Abstract	Functional DNA origami nanoparticles (DNA-NPs) are usedas nanocarriersin a variety of biomedical applications including targeted drug deliveryand vaccine development. DNA-NPs can be designed into a broad rangeof nanoarchitectures in one, two, and three dimensions with high structuralfidelity. Moreover, the addressability of the DNA-NPs enables theprecise organization of functional moieties, which improves targeting,actuation, and stability. DNA-NPs are usually functionalized via chemicallymodified staple strands, which can be further conjugated with additionalpolymers and proteins for the intended application. Although thismethod of functionalization is extremely efficient to control thestoichiometry and organization of functional moieties, fewer thanhalf of the permissible sites are accessible through staple modifications.In addition, DNA-NP functionalization rapidly becomes expensive whena high number of functionalizations such as fluorophores for trackingand chemical modifications for stability that do not require spatiallyprecise organization are used. To facilitate the synthesis of functionalDNA-NPs, we propose a simple and robust strategy based on an asymmetricpolymerase chain reaction (aPCR) protocol that allows direct synthesisof custom-length scaffolds that can be randomly modified and/or preciselymodified via sequence design. We demonstrated the potential of ourstrategy by producing and characterizing heavily modified scaffoldstrands with amine groups for dye functionalization, phosphorothioatebonds for stability, and biotin for surface immobilization. We furthervalidated our sequence design approach for precise conjugation ofbiomolecules by synthetizing scaffolds including binding loops andaptamer sequences that can be used for direct hybridization of nucleicacid tagged biomolecules or binding of protein targets.
ISSN	19448244
Journal	ACS Applied Materials & Interfaces
Volume Number	15
PubMed Central reference number	PMC10273176
Issue Number	23
PubMed reference number	37267624
e-ISSN	19448252
DOI	10.1021/acsami.3c05690
Language	English
Publisher	American Chemical Society
Publisher Date	2023-06-02
Access Restriction	Open
Rights License	Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). © 2023 The Authors. Published by American Chemical Society
Subject Keyword	single-stranded DNA DNA origami scaffold asymmetric polymerase chain reaction bioconjugation DNA nanotechnology
Content Type	Text
Resource Type	Article
Subject	Nanoscience and Nanotechnology Medicine Materials Science