THREE-DIMENSIONAL ARCHITECTURES OF COMPLEX SELF-ASSEMBLING RNA PARTICLES

Scripps Research Institute, The, La Jolla CA

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. By taking advantage of the rich repertoire of natural RNA structural motifs, it is presently possible to generate complex artificial RNA nano-structures with interesting potential therapeutic activities. Recently, we have employed a computer-aided approach to design and engineer versatile, programmable, three-dimensional (3D) self-assembling particles made of RNA with precise control over their geometry, size and composition. These structurally complex RNA particles can be produced with good yields. As anticipated by our theoretical modeling approach, various biochemical characterization techniques suggest that these 3D particles of RNA might adopt the shape of small cubes or cuboids. However, cryo-EM characterization is necessary to validate non-ambiguously their overall 3D architectures. These RNA particles can potentially serve as nano-scaffolds for various therapeutic functions such as RNA aptamers and siRNAs. They have therefore a great potential for biomedical applications.