Small Molecule-Templated DNA Hydrogel with Record Stiffness Integrates and Releases DNA Nanostructures and Gene Silencing Nucleic Acids

Overview

Journal Adv Sci (Weinh)

Specialty Biomedical Engineering

Date 2023 Feb 8

PMID 36752390

Authors

Christophe Lachance-Brais

Mostafa Rammal

Jathavan Asohan

Adam Katolik

Xin Luo

Daniel Saliba

Antranik Jonderian

Masad J Damha

Matthew J Harrington

Hanadi F Sleiman

Affiliations

Soon will be listed here.

Abstract

Deoxyribonucleic acid (DNA) hydrogels are a unique class of programmable, biocompatible materials able to respond to complex stimuli, making them valuable in drug delivery, analyte detection, cell growth, and shape-memory materials. However, unmodified DNA hydrogels in the literature are very soft, rarely reaching a storage modulus of 10 Pa, and they lack functionality, limiting their applications. Here, a DNA/small-molecule motif to create stiff hydrogels from unmodified DNA, reaching 10 Pa in storage modulus is used. The motif consists of an interaction between polyadenine and cyanuric acid-which has 3-thymine like faces-into multimicrometer supramolecular fibers. The mechanical properties of these hydrogels are readily tuned, they are self-healing and thixotropic. They integrate a high density of small, nontoxic molecules, and are functionalized simply by varying the molecule sidechain. They respond to three independent stimuli, including a small molecule stimulus. These stimuli are used to integrate and release DNA wireframe and DNA origami nanostructures within the hydrogel. The hydrogel is applied as an injectable delivery vector, releasing an antisense oligonucleotide in cells, and increasing its gene silencing efficacy. This work provides tunable, stimuli-responsive, exceptionally stiff all-DNA hydrogels from simple sequences, extending these materials' capabilities.

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Small Molecule-Templated DNA Hydrogel with Record Stiffness Integrates and Releases DNA Nanostructures and Gene Silencing Nucleic Acids.

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References

Rahbani J, Hariri A, Cosa G, Sleiman H . Dynamic DNA Nanotubes: Reversible Switching between Single and Double-Stranded Forms, and Effect of Base Deletions. ACS Nano. 2015; 9(12):11898-908. DOI: 10.1021/acsnano.5b04387. View

Linko V, Eerikainen M, Kostiainen M . A modular DNA origami-based enzyme cascade nanoreactor. Chem Commun (Camb). 2015; 51(25):5351-4. DOI: 10.1039/c4cc08472a. View

Shao Y, Jia H, Cao T, Liu D . Supramolecular Hydrogels Based on DNA Self-Assembly. Acc Chem Res. 2017; 50(4):659-668. DOI: 10.1021/acs.accounts.6b00524. View

Pei H, Liang L, Yao G, Li J, Huang Q, Fan C . Reconfigurable three-dimensional DNA nanostructures for the construction of intracellular logic sensors. Angew Chem Int Ed Engl. 2012; 51(36):9020-4. DOI: 10.1002/anie.201202356. View

Kim S, Fan J, Lee C, Chen C, Lee M . Sulfonate Hydrogel-siRNA Conjugate Facilitates Osteogenic Differentiation of Mesenchymal Stem Cells by Controlled Gene Silencing and Activation of BMP Signaling. ACS Appl Bio Mater. 2021; 4(6):5189-5200. PMC: 8513506. DOI: 10.1021/acsabm.1c00369. View

Li C, Chen P, Shao Y, Zhou X, Wu Y, Yang Z . A writable polypeptide-DNA hydrogel with rationally designed multi-modification sites. Small. 2014; 11(9-10):1138-43. DOI: 10.1002/smll.201401906. View

Kalota A, Karabon L, Swider C, Viazovkina E, Elzagheid M, Damha M . 2'-deoxy-2'-fluoro-beta-D-arabinonucleic acid (2'F-ANA) modified oligonucleotides (ON) effect highly efficient, and persistent, gene silencing. Nucleic Acids Res. 2006; 34(2):451-61. PMC: 1342038. DOI: 10.1093/nar/gkj455. View

Lok C, Viazovkina E, Min K, Nagy E, Wilds C, Damha M . Potent gene-specific inhibitory properties of mixed-backbone antisense oligonucleotides comprised of 2'-deoxy-2'-fluoro-D-arabinose and 2'-deoxyribose nucleotides. Biochemistry. 2002; 41(10):3457-67. DOI: 10.1021/bi0115075. View

Zhou X, Li C, Shao Y, Chen C, Yang Z, Liu D . Reversibly tuning the mechanical properties of a DNA hydrogel by a DNA nanomotor. Chem Commun (Camb). 2016; 52(70):10668-71. DOI: 10.1039/c6cc04724f. View

10.

Wang L, Chung J, Li E, Uman S, Atluri P, Burdick J . Injectable and protease-degradable hydrogel for siRNA sequestration and triggered delivery to the heart. J Control Release. 2018; 285:152-161. PMC: 6134398. DOI: 10.1016/j.jconrel.2018.07.004. View

11.

Li C, Rowland M, Shao Y, Cao T, Chen C, Jia H . Responsive Double Network Hydrogels of Interpenetrating DNA and CB[8] Host-Guest Supramolecular Systems. Adv Mater. 2015; 27(21):3298-304. DOI: 10.1002/adma.201501102. View

12.

Ahn S, Kim J, Vellampatti S, Oh S, Lim Y, Park S . Protein-Encoding Free-Standing RNA Hydrogel for Sub-Compartmentalized Translation. Adv Mater. 2022; 34(18):e2110424. DOI: 10.1002/adma.202110424. View

13.

Pashuck E, Duchet B, Hansel C, Maynard S, Chow L, Stevens M . Controlled Sub-Nanometer Epitope Spacing in a Three-Dimensional Self-Assembled Peptide Hydrogel. ACS Nano. 2016; 10(12):11096-11104. DOI: 10.1021/acsnano.6b05975. View

14.

Yuan T, Shao Y, Zhou X, Liu Q, Zhu Z, Zhou B . Highly Permeable DNA Supramolecular Hydrogel Promotes Neurogenesis and Functional Recovery after Completely Transected Spinal Cord Injury. Adv Mater. 2021; 33(35):e2102428. DOI: 10.1002/adma.202102428. View

15.

Seiffert S, Sprakel J . Physical chemistry of supramolecular polymer networks. Chem Soc Rev. 2011; 41(2):909-30. DOI: 10.1039/c1cs15191f. View

16.

Lachance-Brais C, Hennecker C, Alenaizan A, Luo X, Toader V, Taing M . Tuning DNA Supramolecular Polymers by the Addition of Small, Functionalized Nucleobase Mimics. J Am Chem Soc. 2021; 143(47):19824-19833. DOI: 10.1021/jacs.1c08972. View

17.

Highley C, Rodell C, Burdick J . Direct 3D Printing of Shear-Thinning Hydrogels into Self-Healing Hydrogels. Adv Mater. 2015; 27(34):5075-9. DOI: 10.1002/adma.201501234. View

18.

Zhang J, Guo Y, Pan G, Wang P, Li Y, Zhu X . Injectable Drug-Conjugated DNA Hydrogel for Local Chemotherapy to Prevent Tumor Recurrence. ACS Appl Mater Interfaces. 2020; 12(19):21441-21449. DOI: 10.1021/acsami.0c03360. View

19.

Simmel F, Yurke B, Singh H . Principles and Applications of Nucleic Acid Strand Displacement Reactions. Chem Rev. 2019; 119(10):6326-6369. DOI: 10.1021/acs.chemrev.8b00580. View

20.

Yue L, Wang S, Wulf V, Willner I . Stiffness-switchable DNA-based constitutional dynamic network hydrogels for self-healing and matrix-guided controlled chemical processes. Nat Commun. 2019; 10(1):4774. PMC: 6803638. DOI: 10.1038/s41467-019-12697-2. View