Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, UK.
Institute of Biomedical Engineering, University of Oxford, Oxford, OX3 7DQ, UK.
Nucleic Acids Res. 2021 Sep 20;49(16):9042-9052. doi: 10.1093/nar/gkab720.
Rolling circle amplification (RCA) is a powerful tool for the construction of DNA nanomaterials such as hydrogels, high-performance scaffolds and DNA nanoflowers (DNFs), hybrid materials formed of DNA and magnesium pyrophosphate. Such DNA nanomaterials have great potential in therapeutics, imaging, protein immobilisation, and drug delivery, yet limited chemistry is available to expand their functionality. Here, we present orthogonal strategies to produce densely modified RCA products and DNFs. We provide methods to selectively modify the DNA component and/or the protein cargo of these materials, thereby greatly expanding the range of chemical functionalities available to these systems. We have used our methodology to construct DNFs bearing multiple surface aptamers and peptides capable of binding to cancer cells that overexpress the HER2 oncobiomarker, demonstrating their potential for diagnostic and therapeutic applications.
滚环扩增（RCA）是构建 DNA 纳米材料（如水凝胶、高性能支架和 DNA 纳米花（DNF））的强大工具，这些 DNA 纳米材料是由 DNA 和焦磷酸镁形成的杂交材料。此类 DNA 纳米材料在治疗、成像、蛋白质固定和药物输送方面具有巨大的潜力，但可用的化学方法有限，无法扩展其功能。在这里，我们提出了正交策略来生产高密度修饰的 RCA 产物和 DNF。我们提供了选择性修饰这些材料的 DNA 成分和/或蛋白质载体的方法，从而极大地扩展了这些系统可用的化学功能范围。我们已经使用我们的方法构建了带有多个表面适体和能够与过表达 HER2 肿瘤生物标志物的癌细胞结合的肽的 DNF，展示了它们在诊断和治疗应用中的潜力。
