Programmable Site-Specific Functionalization of DNA Origami with Polynucleotide Brushes

• Type of Material: Article
• Authors: Yunqi Yang, Duke University; Qinyi Lu, Emory University; Chao-Min Huang, Duke University; Hongji Qian, Duke University; Yunlong Zhang, Emory University; Sonal Deshpande, Duke University; Gaurav Arya, Duke University; Yonggang Ke, Emory University; Stefan Zauscher, Duke University
• Language: English
• Date: 2021-08-24
• Publisher: WILEY-V C H VERLAG GMBH
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2021 Wiley‐VCH GmbH
• Final Published Version (URL): http://dx.doi.org/10.1002/anie.202107829
• Title of Journal or Parent Work: ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
• Volume: 60
• Issue: 43
• Start Page: 23241
• End Page: 23247
• Keywords: PROTECTION; surface-initiated polymerization; Physical Sciences; drug delivery; CANCER-THERAPY; NANOSTRUCTURES; Chemistry; DNA nanotechnology; FABRICATION; Science & Technology; SIMULATIONS; molecular dynamics simulations; DELIVERY-SYSTEM; NANOMEDICINE; Chemistry, Multidisciplinary; ENZYMATIC POLYMERIZATION; nuclease resistance; CHALLENGES

Abstract

Combining surface-initiated, TdT (terminal deoxynucleotidyl transferase) catalyzed enzymatic polymerization (SI-TcEP) with precisely engineered DNA origami nanostructures (DONs) presents an innovative pathway for the generation of stable, polynucleotide brush-functionalized DNA nanostructures. We demonstrate that SI-TcEP can site-specifically pattern DONs with brushes containing both natural and non-natural nucleotides. The brush functionalization can be precisely controlled in terms of the location of initiation sites on the origami core and the brush height and composition. Coarse-grained simulations predict the conformation of the brush-functionalized DONs that agree well with the experimentally observed morphologies. We find that polynucleotide brush-functionalization increases the nuclease resistance of DONs significantly, and that this stability can be spatially programmed through the site-specific growth of polynucleotide brushes. The ability to site-specifically decorate DONs with brushes of natural and non-natural nucleotides provides access to a large range of functionalized DON architectures that would allow for further supramolecular assembly, and for potential applications in smart nanoscale delivery systems.