![]() ![]() As part of the NCI’s effort to promote the RNA nanotechnology field, a Workshop on RNA and Disease was organized by the pioneer of computational RNA nanotechnology, Bruce Shapiro. (33) More importantly, when three papers exemplifying the use of RNA nanotechnology to treat cancer were published, (34-36) the NCI Alliance in Cancer Nanotechnology, led by Piotr Grodzinski, recognized the potential of RNA nanotechnology in cancer treatment ( ). Subsequently, the editors of Science perceived the importance of RNA nanotechnology and published Luc Jaeger’s paper on tectoRNA (32) with commentary by Hao Yan. (29-31) In 2004, when another empirical paper on RNA nanotechnology was published in Nano Letters, the editor and reporters of MSNBC published a groundbreaking news story entitled “ Scientists build tiny structures out of RNA” to promote this concept of RNA nanotechnology. (27, 28) The original concept of “TectoRNA” or RNA “Tetonics” has led to empirical results in RNA nanotechnology. ![]() In the early 2000s, a group led by Eric Westhof predicted that the RNA kissing loop would promote the formation of special RNA structures. (26) This Molecular Cell paper revealed the ability to engineer RNA into precise constructs to build concise RNA architecture such as dimers, trimers, and hexamers via bottom-up self-assembly, thus showing the concept of RNA nanotechnology. The editors at Cell asked Guo to recommend an authority in the field to review this finding, and Roger Hendrix was chosen. Thus, this significant discovery was published in Molecular Cell (2) with a mini-review in Cell to feature the work. They recognized that this important finding would promote the visibility of their newly initiated journal Molecular Cell. In 1998, Peixuan submitted a manuscript (2) to Cell, reporting his finding of the assembly of pRNA (packaging RNA) dimers, trimers, and hexamers using re-engineered RNA fragments the Cell associate editor, Vivian Siegel, and the founding editor of Cell, Benjamin Lewin, immediately were intrigued. The emergence and advancement of the RNA nanotechnology field is not a simple incidence of the work by one single person but rather a collective effort of many insightful individuals. This review aims to outline the current state of the art of RNA nanoparticles as programmable smart complexes and offers perspectives on the promising avenues of research in this fast-growing field. Other applications of RNA nanotechnology, such as adapting them to construct 2D, 3D, and 4D structures for use in tissue engineering, biosensing, resistive biomemory, and potential computer logic gate modules, have stimulated the interest of the scientific community. The rising popularity of RNA nanoparticles is due to a number of factors: (1) removing the concern of RNA degradation in vitro and in vivo by introducing chemical modification into nucleotides without significant alteration of the RNA property in folding and self-assembly (2) confirming the concept that RNA displays very high thermodynamic stability and is suitable for in vivo trafficking and other applications (3) obtaining the knowledge to tune the immunogenic properties of synthetic RNA constructs for in vivo applications (4) increased understanding of the 4D structure and intermolecular interaction of RNA molecules (5) developing methods to control shape, size, and stoichiometry of RNA nanoparticles (6) increasing knowledge of regulation and processing functions of RNA in cells (7) decreasing cost of RNA production by biological and chemical synthesis and (8) proving the concept that RNA is a safe and specific therapeutic modality for cancer and other diseases with little or no accumulation in vital organs. ![]() A variety of programmable RNA nanoparticles with defined shape, size, and stoichiometry have been developed for diverse applications in nanobiotechnology. The field of RNA nanotechnology has advanced rapidly during the past decade.
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