Poster abstracts
Poster number 83 submitted by Hui Li
Controllable self-assembly of molecularly defined RNA tetrahedrons for cancer targeting and therapeutics delivery
Hui Li (Division of Pharmaceutics and Pharmaceutical Chemistry; Department of Physiology & Cell Biology/Dorothy M. Davis Heart and Lung Research Institute; The Ohio State University), Kaiming Zhang (Verna and Marrs McLean Department of Biochemistry and Molecular Biology, National Center for Macromolecular Imaging, Baylor College of Medicine), Fengmei Pi, Sijin Guo, Dan Shu (Division of Pharmaceutics and Pharmaceutical Chemistry; Department of Physiology & Cell Biology/Dorothy M. Davis Heart and Lung Research Institute; The Ohio State University), Luda Shlyakhtenko (Department of Pharmaceutical Sciences, University of Nebraska Medical Center), Wah Chiu (Verna and Marrs McLean Department of Biochemistry and Molecular Biology, National Center for Macromolecular Imaging, Baylor College of Medicine), Peixuan Guo (Division of Pharmaceutics and Pharmaceutical Chemistry; Department of Physiology & Cell Biology/Dorothy M. Davis Heart and Lung Research Institute; The Ohio State University)
Abstract:
Since RNA shows an integer of 11 nucleotides per helix turn of 360°, in comparison to DNA that shows a non-integer of 10.5 nucleotides per helix turn, we propose that different sizes of RNA 3D structures can be constructed with precise control and the size of the particle will increase linearly by increasing the nucleotide number as multiples of eleven. Herein, we used the ultra-stable pRNA-3WJ motif with controllable angles and arm lengths to construct tetrahedral architectures composed purely of RNA via one-pot bottom-up assembly with high efficiency and thermal stability. By introducing arm sizes of 22 bp and 55 bp, respectively, we constructed two RNA tetrahedrons with similar global contour structure but with different sizes of 8 nm and 17 nm, respectively. AFM and cryo-EM imaging clearly demonstrated the 3D shapes of RNA tetrahedrons that were consistent with the designs. The RNA tetrahedrons were also highly amenable to functionalization. Fluorogenic RNA aptamers, ribozyme, siRNA, and protein-binding RNA aptamers were integrated into the tetrahedrons by simply fusing the respective sequences with the tetrahedral core modules. Upon systemic injection, 2'-F modified RNase resistant RNA tetrahedrons harboring EGFR aptamers specifically targeted orthotopic breast tumors without getting trapped in healthy organs. The favorable biodistribution highlight their potentials as safe and specific drug delivery vectors. The reported design principles can be extended to construct higher order polyhedral RNA architectures for various applications in nanomedicine and nanotechnology.
References:
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3. Li H, Lee T, Dziubla T, Pi F; Guo S, Xu J, Li C, Haque F, Liang, X-J, Guo P. RNA as a Stable Polymer to Build Controllable and Defined Nanostructures for Material and Biomedical Applications. Nano Today. 2015; 10:631.
4. Li H, Zhang K, Pi F, Guo S, Shlyakhtenko L, Chiu W, Shu D, Guo P. Controllable Self-Assembly of RNA Tetrahedrons with Precise Shape and Size for Cancer Targeting. Advanced Materials. 2016;28:7501.
Keywords: RNA Nanotechnology, Bacteriophage Phi29 pRNA, RNA Nanoparticles