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Advance could speed RNA nanotechnology

A news item on Technology Networks (free registration required) implies that RNA might be ready to join its more famous chemical cousin DNA as a promising path to developing advanced nanotechnology. From Advance could Speed use of Genetic Material RNA in Nanotechnology:

Scientists are reporting an advance in overcoming a major barrier to the use of the genetic material RNA in nanotechnology — the field that involves building machines thousands of times smaller than the width of a human hair. An area that is currently dominated by its cousin, DNA.

Their findings, which could speed the use of RNA nanotechnology for treating disease, appear in the monthly journal ACS Nano [Fabrication of Stable and RNase-Resistant RNA Nanoparticles Active in Gearing the Nanomotors for Viral DNA Packaging].

Peixuan Guo and colleagues point out that DNA, the double-stranded genetic blueprint of life, and RNA, its single-stranded cousin, share common chemical features that can serve as building blocks for making nanostructures and nanodevices. In some ways, RNA even has advantages over DNA. The field of DNA nanotechnology is already well-established, they note. The decade-old field of RNA nanotechnology shows great promise, with potential applications in the treatment of cancer, viral, and genetic diseases. However, the chemical instability of RNA and its tendency to breakdown in the presence of enzymes have slowed progress in the field

The scientists describe development of a highly stable RNA nanoparticle. …

The abstract of the ACS Nano paper concisely states why RNA offers several potential advantages compared to DNA, and what they have accomplished:

Both DNA and RNA can serve as powerful building blocks for bottom-up fabrication of nanostructures. A pioneering concept proposed by Ned Seeman 30 years ago has led to an explosion of knowledge in DNA nanotechnology. RNA can be manipulated with simplicity characteristic of DNA, while possessing noncanonical base-pairing, versatile function, and catalytic activity similar to proteins. However, standing in awe of the sensitivity of RNA to RNase degradation has made many scientists flinch away from RNA nanotechnology. Here we report the construction of stable RNA nanoparticles resistant to RNase digestion. The 2′-F (2′-fluoro) RNA retained its property for correct folding in dimer formation, appropriate structure in procapsid binding, and biological activity in gearing the phi29 nanomotor to package viral DNA and producing infectious viral particles. Our results demonstrate that it is practical to produce RNase-resistant, biologically active, and stable RNA for application in nanotechnology.

The potential advantages of RNA for making building blocks for advanced nanotechnology stem from its hypothesized primordial role in the pre-biotic evolution of life (see RNA world hypothesis). While RNA shares with DNA the molecular recognition properties essential for a role in replicating genetic information, its more versatile chemical nature also facilitates catalytic functions, like proteins. However, this chemical versatility also renders RNA much more susceptible to both chemical and enzymatic degradation (by enzymes called RNases), making RNA difficult to work with (a fact to which I can personally testify having spent most of my research career working with RNA) and presumably accounting for why evolution chose DNA as the genetic material for everything larger than some smaller viruses. Among the many biological roles that RNA molecules fill is the one Prof. Guo and his colleagues have worked with for many years—gearing a powerful nanomotor that packages viral DNA into the protein shells of a bacterial virus named phi29. By constructing the RNA building blocks for this gearing out of RNA subunits that have been chemically modified (substituting a fluorine atom for the 2′-hydroxyl group of the ribose sugar) to resist degradation, and showing that this RNA molecule still folds properly and still functions to make infectious virus particles, Guo and his colleagues have cleared a path for more thorough exploitation of the unique properties of RNA.

An open access review by Peixuan Guo of the potential of RNA Nanotechnology, published in 2005, can be found here. Another RNA nanotechnology pioneer, Luc Jaeger, published a paper in 2009 “Defining the syntax for self-assembling RNA tertiary architectures” (open access version) focused on “RNA architectonics” to decipher the code needed to “build new functional RNA shapes with self-assembly properties”. These studies “demonstrate that small structural motifs can potentially code for the precise topology of an almost infinite variety of large molecular architectures. Ultimately, it is anticipated that RNA particles with the structural complexity of the ribosome could be generated through RNA architectonics.” It will be interesting to watch over the next several years if this variety of 3D structures leads to useful structures and devices for the development of molecular machine systems and ultimately productive nanosystems.

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