Um Soong Ho, Lee Jong Bum, Park Nokyoung, Kwon Sang Yeon, Umbach Christopher C, Luo Dan
Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York 14853-5701, USA.
Nat Mater. 2006 Oct;5(10):797-801. doi: 10.1038/nmat1741. Epub 2006 Sep 24.
DNA is a remarkable polymer that can be manipulated by a large number of molecular tools including enzymes. A variety of geometric objects, periodic arrays and nanoscale devices have been constructed. Previously we synthesized dendrimer-like DNA and DNA nanobarcodes from branched DNA via ligases. 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 hydrogels) 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.
DNA是一种非凡的聚合物,可通过包括酶在内的大量分子工具进行操控。人们已经构建了各种几何物体、周期性阵列和纳米级器件。此前我们通过连接酶从分支DNA合成了树枝状DNA和DNA纳米条形码。在此我们报告一种完全由分支DNA构建的水凝胶,其具有三维结构且本质上可交联。这些DNA水凝胶具有生物相容性、可生物降解、制备成本低廉且易于成型为所需的形状和尺寸。DNA水凝胶与其他仿生水凝胶(包括基于肽的、基于藻酸盐的以及DNA(线性)-聚丙烯酰胺水凝胶)的显著区别在于交联是通过高效的连接酶介导反应实现的。其优势在于凝胶化过程在生理条件下完成,并且包封在原位进行——包括蛋白质甚至活的哺乳动物细胞在内的药物都可以在液相中被包封,从而省去了药物负载步骤,同时也避免了变性条件。通过调整分支DNA单体的初始浓度和类型,这些水凝胶很容易实现精细调节,从而使水凝胶能够针对特定应用进行定制,如控释药物、组织工程、3D细胞培养、细胞移植治疗及其他生物医学应用。