RNA nanotechnology employs synthetically modified ribonucleic acid to engineer highly stable nanostructures in one, two, and three dimensions for medical applications. Despite the tremendous advantages in this field, it is uncertain whether chemically modified RNA nanoparticles and their metabolic products are toxic to an organism creating significant problem in further applications. In contrast, we used naturally occurring nucleic acids and developed RNA/DNA hybrid approach to address questions related to assembly efficiency, thermal and enzymatic stability, as well as exploited their potential to serve as a cargo for delivery of silencing RNA. A computer-assisted<i> de novo</i> RNA tetra-uracil/thymine (tetra-U/T) helix linking module (motif) was fabricated to construct four functional equilateral triangles of ~12 nm size using RNA, DNA and RNA/DNA mixtures. We demonstrate their enzymatic and thermodynamic stabilities, immunostimulatory activity and siRNA delivery can be regulated by the ratio of DNA and RNA within the triangular nano-scaffold. We also demonstrate that tetra-U/T motif has great potential in the fabrication of rectangular, pentagonal, and hexagonal nanostructures confirmed by AFM, representing the power of simplicity of RNA/DNA approach for RNA nanotechnology and nanomedicine community. The technique shown here for a simple design to precisely tune physicochemical properties adds a new angle to exploit RNA/DNA hybrid nanoparticles in a clinical setting.

Nucleic acid nano-vehicles designed form flexible tetra-U/T helix linking motif

2019 Spring National Meeting

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