Distinguished iNANO Lecture: Creating Dynamic Organization with DNA Nanotechnology

Chunhai Fan, Division of Physical Biology, and Bioimaging Center, Shanghai Synchrotron Radiation Facility, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, China

Creating Dynamic Organization with DNA Nanotechnology

Proteins and nucleic acids are dynamically organized in cells to realize their physiological functions with spatial and temporal orderliness. This type of elegant supermolecular assembly has inspired researchers to create molecular/biomolecular structures with dynamic organization outside of the cells. In particular, DNA nanotechnology has proven to possess extraordinary flexibility and convenience for “bottom-up” construction of exquisite nanostructures with high controllability and precision, which holds great promise in a wide range of applications, e.g., nanofabrication and molecular electronics, in-vivo and in-vitro sensing and drug delivery.

In this talk, I will present several examples of using tetrahedral DNA nanostructures (TDNs) for dynamic organization of biomolecules in vitro. TDNs are three-dimensional (3D) DNA architecture with high mechanical rigidity and structural stability, which are suitable for organization of higher-ordered nanocomplexes and nanodevices. As one of the examples, I will describe how we use TDNs as nanoscale agents for both intracellular imaging and efficient delivery of therapeutic oligonucleotides. We employed single-particle tracking to visualize the internalization of TDNs, and dissect the cell entry pathways of these virus-like nanoparticles. In the second example, I hope to use the way that we employed TDNs to dynamically organize the biosensing interface, and realize macroscopic applications on diagnostics. A critical challenge in surface-based biomolecular detection is the reduced accessibility of target molecules to probes arranged on heterogeneous surface compared to probe-target recognition in homogeneous solution. We improve probe-target recognition properties by introducing a probe bearing a TDN-based platform, which provides significantly enhanced spatial positioning range and accessibility of the probes on surface. We also show the versatility of this TDN-based platform for the detection of a wide range of tumor-associated biomarkers.

References

1. Li, D., Song, S. and Fan, C. (2010) Target-responsive structures for nucleic acid sensors. Acc. Chem. Res., 43, 631.
2. Pei, H., Lu, N., Wen, Y., Song, S., Liu, Y., Yan, H. and Fan, C. (2010) A DNA Nanostructure-based Biomolecular Probe Carrier Platform for Electrochemical Biosensing. Adv. Mater., 22, 4754.
3. Li, J., Pei, H., Zhu, B., Liang, L., Wei, M., He, Y., Chen, N., Li, D., Huang, Q. and Fan, C. (2011) Self-Assembled Multivalent DNA Nanostructures for Noninvasive Intracellular Delivery of Immunostimulatory CpG Oligonucleotides. ACS Nano, 5, 8783.
4. Pei, H., Liang, L., Yao, G., Li, J., Huang, Q. and Fan, C. (2012) Reconfigurable Three-Dimensional DNA Nanostructures for the Construction of Intracellular Logic Sensors. Angew. Chem. Int. Ed., 51, 9020.
5. Lu, N., Pei, H., Ge, Z., Simmons, C., Yan, H. and Fan, C. (2012) Charge transport within a three-dimensional DNA nanostructure framework. J. Am. Chem. Soc., 134, 13148.
6. Fu, Y., Zeng, D., Chao, J., Jin, Y., Zhang, Z., Liu, H., Li, D., Ma, H., Huang, Q., Gothelf, K.V. and Fan, C. (2013) Single-Step Rapid Assembly of DNA Origami Nanostructures for Addressable Nanoscale Bioreactors. J. Am. Chem. Soc., 135, 696.
7. Liang, L., Li, J., Li, Q., Huang, Q., Shi, J., Yan, H. and Fan, C. (2014) Single-particle tracking and modulation of cell entry pathways of a tetrahedral DNA nanostructure in live cells. Angew. Chem. Int. Ed., 53, 7745.
8. Chen, N., Li, J., Song, H., Chao, J., Huang, Q. and Fan, C. (2014) Physical and Biochemical Insights on DNA Structures in Artificial and Living Systems. Acc. Chem. Res. 47, 1720. 

Short biography:

Chunhai Fan obtained his B.S. and Ph.D. from the Department of Biochemistry at NanjingUniversity in 1996 and 2000. After his postdoctoral research at University of California, Santa Barbara (UCSB), he joined the faculty at Shanghai Institute of Applied Physics (SINAP), ChineseAcademy of Sciences (CAS) in 2004. He is now Professor and Chief of the Division of Physical Biology at SINAP and the Bioimaging Center of Shanghai Synchrotron Radiation Facility (SSRF). He is an elected fellow of the International Society of Electrochemistry (ISE). He is also an Associate Editor of ACS Applied Materials & Interfaces, a Guest Editor of Advanced Materials, and serves on the editorial board of several international journals (Scientific Reports, Advanced Healthcare Materials, Journal of Materials Chemistry, Electroanalysis, Particles etc.). Dr. Fan has published ~300 papers in peer-reviewed journals, and he was recently recognized as High Cited Researchers in 2014 by Thomson Reuters.

Host:  Professor Kurt V. Gothelf, iNANo & Department of Chemistry, Aarhus University

Coffe, tea and bread will be served from 10:00 in front of the auditorium