Halman Justin R, Satterwhite Emily, Roark Brandon, Chandler Morgan, Viard Mathias, Ivanina Anna, Bindewald Eckart, Kasprzak Wojciech K, Panigaj Martin, Bui My N, Lu Jacob S, Miller Johann, Khisamutdinov Emil F, Shapiro Bruce A, Dobrovolskaia Marina A, Afonin Kirill A
Nanoscale Science Program, Department of Chemistry, University of North Carolina at Charlotte, Charlotte, NC 28223, USA.
RNA Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.
Nucleic Acids Res. 2017 Feb 28;45(4):2210-2220. doi: 10.1093/nar/gkx008.
We introduce a new concept that utilizes cognate nucleic acid nanoparticles which are fully complementary and functionally-interdependent to each other. In the described approach, the physical interaction between sets of designed nanoparticles initiates a rapid isothermal shape change which triggers the activation of multiple functionalities and biological pathways including transcription, energy transfer, functional aptamers and RNA interference. The individual nanoparticles are not active and have controllable kinetics of re-association and fine-tunable chemical and thermodynamic stabilities. Computational algorithms were developed to accurately predict melting temperatures of nanoparticles of various compositions and trace the process of their re-association in silico. Additionally, tunable immunostimulatory properties of described nanoparticles suggest that the particles that do not induce pro-inflammatory cytokines and high levels of interferons can be used as scaffolds to carry therapeutic oligonucleotides, while particles with strong interferon and mild pro-inflammatory cytokine induction may qualify as vaccine adjuvants. The presented concept provides a simple, cost-effective and straightforward model for the development of combinatorial regulation of biological processes in nucleic acid nanotechnology.
我们引入了一种新的概念，该概念利用了同源核酸纳米颗粒，这些纳米颗粒彼此完全互补且功能相互依赖。在所描述的方法中，设计的纳米颗粒组之间的物理相互作用引发快速的等温形状变化，从而触发多种功能和生物途径的激活，包括转录、能量转移、功能性适配体和RNA干扰。单个纳米颗粒不具有活性，并且具有可控的重新结合动力学以及可精细调节的化学和热力学稳定性。开发了计算算法以准确预测各种组成的纳米颗粒的解链温度，并在计算机上追踪它们重新结合的过程。此外，所描述的纳米颗粒的可调免疫刺激特性表明，不诱导促炎细胞因子和高水平干扰素的颗粒可作为携带治疗性寡核苷酸的支架，而具有强烈干扰素诱导和轻度促炎细胞因子诱导的颗粒可能符合疫苗佐剂的条件。所提出的概念为核酸纳米技术中生物过程的组合调控开发提供了一个简单、经济高效且直接的模型。
