21ENGBIO Controllable DNA polycatenanes of infinite length for intelligent biomaterials

21ENGBIO 用于智能生物材料的无限长度可控 DNA 聚链烷

• 批准号: BB/W01338X/1
• 负责人: Susan Rosser
• 金额: $ 12.85万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FW01338X%2F1
• 关键词: 21ENGBIO; Controllable; DNA; polycatenanes; infinite

DNA is an ideal substrate from which to construct new materials for medical applications because it is sustainable, biodegradable, biocompatible, non-toxic, and highly programmable. DNA hydrogels have state-of-the-art applications in regenerative therapy (like stimulating new tissue growth from stem cells) and biologics delivery (like controlled, sustained release of insulin). They are squishy, gel-like materials made of water and web-like structures of DNA, and they can obtain unique properties when combined with nanomaterials. The disadvantages of current DNA hydrogels are in how their web-like structures of DNA are held together. Many rely on the ability of compatible DNA strands to stick together but this stickiness is susceptible changes in environmental conditions such as an increase in temperature which causes the structures to unravel. Adding small molecules to reinforce the DNA structures through cross-linking increases the manufacturing time and cost. Here, we will synthesise never-before-made DNA-based materials from polycatenanes. Polycatenanes are polymers in which molecular rings are mechanically linked together akin to the links of a chain. We have devised a strategy to make DNA polycatenanes of infinite and controllable lengths using enzymes to connect rings of DNA. In addition to enabling assembly 1D DNA chains, our strategy will enable construction of 2D and 3D DNA structures that require no cross-linking small molecules and will not unravel upon changes in environmental conditions. This work aims to seed development of a new family of structurally unique DNA-based biomaterials for programmable biologics delivery and patient-specific regenerative therapies.

DNA是构建医学应用新材料的理想底物，因为它具有可持续性、可生物降解、生物相容性、无毒和高度可编程性。DNA水凝胶在再生治疗（如刺激干细胞的新组织生长）和生物制剂输送（如控制胰岛素的持续释放）方面有着最先进的应用。它们是由水和网状DNA结构组成的柔软的凝胶状材料，当与纳米材料结合时，它们可以获得独特的性能。目前DNA水凝胶的缺点在于它们的网状DNA结构是如何结合在一起的。许多人依靠兼容的DNA链粘在一起的能力，但这种粘在一起的能力很容易受到环境条件变化的影响，比如温度升高，这会导致结构解体。添加小分子通过交联来增强DNA结构增加了制造时间和成本。在这里，我们将从聚连环烷合成前所未有的dna基材料。聚连环烷是一种聚合物，其分子环机械地连接在一起，类似于链的链接。我们已经设计出一种策略，利用酶连接DNA环，制造出无限和可控长度的DNA聚连环烷。除了能够组装1D DNA链外，我们的策略还将能够构建不需要交联小分子的2D和3D DNA结构，并且在环境条件变化时不会解开。这项工作旨在为可编程生物制剂输送和患者特异性再生治疗提供一种结构独特的基于dna的新生物材料家族。