Sequence-programmable covalent bonding of designed DNA assemblies

被引:195
作者
Gerling, Thomas
Kube, Massimo
Kick, Benjamin
Dietz, Hendrik [1 ]
机构
[1] Tech Univ Munich, Dept Phys, Lab Biomol Design, Munich, Germany
基金
欧洲研究理事会;
关键词
CRYO-EM STRUCTURE; NANOSCALE SHAPES; PYRIMIDINE DIMERS; SKIN-CANCER; FOLDING DNA; ORIGAMI; NANOSTRUCTURES; OLIGONUCLEOTIDES; SPECTROSCOPY; NANOANTENNAS;
D O I
10.1126/sciadv.aau1157
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Bottom-up fabrication of custom nanostructures using the methods of DNA nanotechnology has great potential for applications in many areas of science and technology. One obstacle to applications concerns the constrained environmental conditions at which DNA objects retain their structure. We present a general, site-selective, and scalable method for creating additional covalent bonds that increase the structural stability of DNA nanostructures. Placement of thymidines in close proximity within DNA nanostructures allows the rational creation of sites for covalent cyclobutane pyrimidine dimer (CPD) bonds induced via ultraviolet irradiation. The additional covalent bonds may be used in a sequence-programmable fashion to link free strand termini, to bridge strand breaks at crossover sites, and to create additional interhelical connections. Thus designed multilayer DNA origami objects can remain stable at temperatures up to 90 degrees C and in pure double-distilled water with no additional cations present. In addition, these objects show enhanced resistance against nuclease activity. Cryo-electron microscopy (cryo-EM) structural analysis of non cross-linked and cross-linked objects indicated that the global shape and the internal network of crossovers are preserved after irradiation. A cryo-EM map of a CPD-stabilized multilayer DNA origami object determined at physiological ionic strength reveals a substantial swelling behavior, presumably caused by repulsive electrostatic forces that, without covalent stabilization, would cause disassembly at low ionic strength. Our method opens new avenues for applications of DNA nanostructures in a wider range of conditions.
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页数:11
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