Department of Mechanical Engineering and Materials Science, Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA.
Department of Chemistry, Emory University, Atlanta, GA 30322, USA.
Angew Chem Int Ed Engl. 2023 Nov 27;62(48):e202311727. doi: 10.1002/anie.202311727. Epub 2023 Oct 25.
DNA nanotechnology provides an approach to create precise, tunable, and biocompatible nanostructures for biomedical applications. However, the stability of these structures is severely compromised in biological milieu due to their fast degradation by nucleases. Recently, we showed how enzymatic polymerization could be harnessed to grow polynucleotide brushes of tunable length and location on the surface of DNA origami nanostructures, which greatly enhances their nuclease stability. Here, we report on strategies that allow for both spatial and temporal control over polymerization through activatable initiation, cleavage, and regeneration of polynucleotide brushes using restriction enzymes. The ability to site-specifically decorate DNA origami nanostructures with polynucleotide brushes in a spatiotemporally controlled way provides access to "smart" functionalized DNA architectures with potential applications in drug delivery and supramolecular assembly.
DNA 纳米技术为创建用于生物医学应用的精确、可调谐且生物相容的纳米结构提供了一种方法。然而，由于这些结构在生物环境中会被核酸酶快速降解，因此其稳定性受到严重影响。最近，我们展示了如何利用酶促聚合来在 DNA 折纸纳米结构表面上生长可调长度和位置的多核苷酸刷，这极大地提高了它们的核酸酶稳定性。在这里，我们报告了通过使用限制酶激活起始、切割和再生多核苷酸刷来实现聚合的时空控制的策略。通过这种方式，可以在时空控制的方式下将多核苷酸刷特异性地修饰 DNA 折纸纳米结构，这为具有潜在药物输送和超分子组装应用的“智能”功能化 DNA 结构提供了可能。
