Li Yu, Zheng Haoran, Lu Hui, Duan Mulin, Li Cong, Li Mingqiang, Li Jiang, Wang Lihua, Li Qian, Chen Jing, Shen Jianlei
Division of Physical Biology, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China.
Department of Stem Cells and Regenerative Medicine, Translational Medicine Research Center, Naval Medical University, 800, Xiangyin Road, Shanghai 200433 ,China.
JACS Au. 2023 Aug 7;3(8):2206-2215. doi: 10.1021/jacsau.3c00252. eCollection 2023 Aug 28.
Nucleic acid condensates are essential for various biological processes and have numerous applications in nucleic acid nanotechnology, gene therapy, and mRNA vaccines. However, unlike the in vivo condensation that is dependent on motor proteins, the in vitro condensation efficiency remains to be improved. Here, we proposed a hydrophobic interaction-driven mechanism for condensing long nucleic acid chains using atomically precise hydrophobic gold nanoclusters (Au NCs). We found that hydrophobic Au NCs could condense long single-stranded DNA or RNA to form composites of spherical nanostructures, which further assembled into bead-shaped suprastructures in the presence of excessive Au NCs. Thus, suprastructures displayed gel-like behaviors, and Au NCs could diffuse freely inside the condensates, which resemble the collective motions of condensin complexes inside chromosomes. The dynamic hydrophobic interactions between Au NCs and bases allow for the reversible release of nucleic acids in the presence of mild triggering agents. Our method represents a significant advancement toward the development of more efficient and versatile nucleic acid condensation techniques.
核酸凝聚物对各种生物过程至关重要，在核酸纳米技术、基因治疗和mRNA疫苗中有众多应用。然而，与依赖马达蛋白的体内凝聚不同，体外凝聚效率仍有待提高。在此，我们提出了一种利用原子精确的疏水金纳米簇（Au NCs）凝聚长核酸链的疏水相互作用驱动机制。我们发现疏水Au NCs可以凝聚长单链DNA或RNA形成球形纳米结构复合物，在过量Au NCs存在下，这些复合物进一步组装成珠状超结构。因此，超结构表现出凝胶状行为，Au NCs可以在凝聚物内部自由扩散，这类似于染色体内部凝聚素复合物的集体运动。Au NCs与碱基之间的动态疏水相互作用使得在温和触发剂存在下核酸能够可逆释放。我们的方法代表了朝着开发更高效、更通用的核酸凝聚技术迈出的重要一步。
