21ENGBIO Controllable DNA polycatenanes of infinite length for intelligent biomaterials

DNA是构建医疗应用新材料的理想底物，因为它具有可持续、可生物降解、生物兼容、无毒和高度可编程的特点。DNA水凝胶在再生治疗(如刺激干细胞新组织生长)和生物制品输送(如受控、持续释放胰岛素)方面具有最先进的应用。它们是由水和DNA的网状结构组成的柔软的凝胶状材料，当它们与纳米材料结合时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。许多依赖于相容的DNA链粘在一起的能力，但这种粘性容易随着环境条件的变化而变化，例如导致结构解体的温度上升。添加小分子通过交联来增强DNA结构会增加制造时间和成本。在这里，我们将从多环戊二烯合成前所未有的基于DNA的材料。聚戊二烯是一种分子环机械连接在一起的聚合物，类似于链的连接。我们设计了一种策略，使用酶连接DNA环，使DNA多环烷具有无限可控的长度。除了能够组装1D DNA链之外，我们的战略还将能够构建2D和3D DNA结构，这些结构不需要交联性小分子，并且不会随着环境条件的变化而解体。这项工作旨在为可编程生物制剂输送和患者特定的再生治疗提供一种新的结构独特的基于DNA的生物材料家族的开发。

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.