Date: Tuesday, February 1, 2022
Time: 11:00 am
Talk Title: RNA Origami: The Art of Folding an RNA Strand to Create Nanoscale Shapes
The RNA origami method enables the rational design of RNA nanostructures that fold from a single strand during transcription by an RNA polymerase . Folding during synthesis is a desired property, since it allows RNA nanostructures to be produced at high quality and yield for applications in RNA medicine or synthetic biology. We have recently developed ROAD (RNA Origami Automated Design), a new software package, that facilitates the design of RNA origami structures by automating the atomic modeling, detecting topological barriers, and designing RNA sequences for the target structure . We demonstrate the capabilities of ROAD by characterizing a large panel of RNA origami structures using atomic force microscopy (AFM), cryo-electron microscopy (cryo-EM), and small-angle X-ray scattering (SAXS), and identify novel structural properties and folding pathways that are used to improve the RNA origami method. For applications, we show that RNA origami can be used to scaffold molecular components with nanoscale precision, and to create functional devices e.g. RNA particles carrying several small interfering RNAs for potent gene knockdown , RNA-based sensor devices using Förster resonance energy transfer (FRET) between light-up aptamers , and RNA scaffolds for thrombin-binding aptamers to function anticoagulation agents .
 Geary, C., Rothemund, P. W. & Andersen, E. S. A single-stranded architecture for cotranscriptional folding of RNA nanostructures. Science 345, 799-804, doi:10.1126/science.1253920 (2014).
 Geary, C., Grossi, G., McRae, E. K. S., Rothemund, P. W. K. & Andersen, E. S. RNA origami design tools enable cotranscriptional folding of kilobase-sized nanoscaffolds. Nat Chem, doi:10.1038/s41557-021-00679-1 (2021).
 Høiberg, H. C., Sparvath, S. M., Andersen, V. L., Kjems, J. & Andersen, E. S. An RNA Origami Octahedron with Intrinsic siRNAs for Potent Gene Knockdown. Biotechnol J, e1700634, doi:10.1002/biot.201700634 (2018).
 Jepsen, M. D. E. et al. Development of a genetically encodable FRET system using fluorescent RNA aptamers. Nature communications 9, 18, doi:10.1038/s41467-017-02435-x (2018).
 Krissanaprasit, A. et al. Genetically Encoded, Functional Single-Strand RNA Origami: Anticoagulant. Adv Mater, e1808262, doi:10.1002/adma.201808262 (2019).
Ebbe Sloth Andersen is an associate professor at the Interdisciplinary Nanoscience Center at Aarhus University, Denmark, and is also affiliated with the Department of Molecular Biology and Genetics. He did his PhD studies on HIV RNA structure and function in the laboratory of Professor Jørgen Kjems at Aarhus Univeristy and did his Postdoc work in the context of the Centre for DNA Nanotechnology lead by Professor Kurt Gothelf. As assistant professor he has been a visiting associate at California Institute of Technology working with Professor Paul Rothemund, inventor of the DNA origami method, to develop the RNA origami methodology. Ebbe has been running his own research group since 2012 with a focus on designing DNA and RNA nanoscale devices for applications in diagnostics, medicine and synthetic biology.