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Enzyme-catalysed assembly of DNA hydrogel

Nature Materials volume 5, pages 797–801 (2006)Cite this article

Abstract

DNA is a remarkable polymer that can be manipulated by a large number of molecular tools including enzymes1. A variety of geometric objects, periodic arrays and nanoscale devices have been constructed2,3,4,5,6,7,8,9,10,11,12,13. Previously we synthesized dendrimer-like DNA and DNA nanobarcodes from branched DNA via ligases14,15. Here we report the construction of a hydrogel entirely from branched DNA that are three-dimensional and can be crosslinked in nature. These DNA hydrogels were biocompatible, biodegradable, inexpensive to fabricate and easily moulded into desired shapes and sizes. The distinct difference of the DNA hydrogel to other bio-inspired hydrogels (including peptide-based, alginate-based and DNA (linear)-polyacrylamide hydrogels16,17,18,19,20) is that the crosslinking is realized via efficient, ligase-mediated reactions. The advantage is that the gelling processes are achieved under physiological conditions and the encapsulations are accomplished in situ—drugs including proteins and even live mammalian cells can be encapsulated in the liquid phase eliminating the drug-loading step and also avoiding denaturing conditions. Fine tuning of these hydrogels is easily accomplished by adjusting the initial concentrations and types of branched DNA monomers, thus allowing the hydrogels to be tailored for specific applications such as controlled drug delivery, tissue engineering, 3D cell culture, cell transplant therapy and other biomedical applications.

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Figure 1: Schematic diagram of BDM and DNA hydrogels.
Figure 2: Hydrogels made entirely from branched DNA.
Figure 3: External morphologies and internal structures of different DNA hydrogels.
Figure 4: Degradation and controlled drug-release profiles of different DNA hydrogels.

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Acknowledgements

We wish to acknowledge financial support from USDA, the Cornell Advanced Technology Centre for Biotechnology, the Nanobiotechnology Center (NSF/ECS-9876771) and the Cornell Center for Materials Research (NSF/DMR-0520404). D.L. acknowledges the NSF CAREER Award and N.P. acknowledges the Korea Research Foundation Grant (04-03-05-2) for partial support. Y. Chang, Y. Zhang and N. Walker are acknowledged for help in animal tests, DMA and data processing, respectively.

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Authors and Affiliations

  1. Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York, 14853-5701, USA

    Soong Ho Um, Jong Bum Lee, Nokyoung Park, Sang Yeon Kwon & Dan Luo

  2. Department of Materials Science and Engineering, Cornell University, Ithaca, New York, 14853-5701, USA

    Christopher C. Umbach

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  1. Soong Ho Um
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Correspondence to Dan Luo.

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The corresponding author (D.L.) is one of the founders of a start-up company that licensed the technology from Cornell University.

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Supplementary tables S1, S2 and S3

Supplementary Information

Supplementary information and figures S1, S2 and S3

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Um, S., Lee, J., Park, N. et al. Enzyme-catalysed assembly of DNA hydrogel. Nature Mater 5, 797–801 (2006). https://doi.org/10.1038/nmat1741

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