Nucleic Acids-Based Nanotechnology: Engineering Principals and Applications

Nucleic Acids-Based Nanotechnology: Engineering Principals and Applications

Robert Penchovsky (Sofia University “St. Kliment Ohridski”, Bulgaria)
DOI: 10.4018/978-1-4666-5824-0.ch016
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Nanobiotechnology is emerging as a valuable field that integrates research from science and technology to create novel nanodevices and nanostructures with various applications in modern nanotechnology. Applications of nanobiotechnology are employed in biomedical and pharmaceutical research, biosensoring, nanofluidics, self-assembly of nanostructures, nanopharmaceutics, molecular computing, and others. It has been proven that nucleic acids are a very suitable medium for self-assembly of diverse nanostructures and catalytic nanodevices for various applications. In this chapter, the authors discuss various applications of nucleic-based nanotechnology. The areas discussed here include building nanostructures using DNA oligonucleodite, self-assembly of integrated RNA-based nanodevices for molecular computing and diagnostics, antibacterial drug discovery, exogenous control of gene expression, and gene silencing.
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Nanotechnology aims to engineer a variety of functional systems at a scale of a few nanometers (Harris et al.). This novel technology presents, in its original meaning, a various methods for building systems from the bottom up at molecular and even atomic level. It is believed that the theoretical envision of nanotechnology was made by Richard Feynman, a Nobel Prize laureate in physics, in his famous lecture entitled “There is a plenty of room at the bottom” in 1959. In his lecture Feynman stated that the laws of physics do not speak against the possibility of creating things atom by atom. The implementation of the idea of molecular manufacturing brings new classes of problems and unfamiliar research areas that are at the core of the emerging field of nanotechnology.

Nowadays, nanotechnology is emerging as a crossing point among the natural and engineering sciences. It is an area of exciting discoveries that includes many different scientific and technological fields. In fact, many natural sciences, including chemistry and biology along with many types of chemical and biological engineering at a molecular and sub-molecular level are involved in nanobiotechnology.

Many scientists believe that function at the nanoscale is an essential element of nanotechnology. As nanotechnology developed, its definition is leading more to the design and engineering of functional systems at the molecular level rather than the design of nanostructures. Nanotechnology is a rapidly improving field that involves several major developments. In general, it includes a creation of passive and active nanostructures, made of many interacting components, and finally leading to integrated nanodevices (Penchovsky, 2012). The passive nanostructures are engineered to perform one particular task, whereas the active structures are designed to execute several different functions. Active nanostructures can be molecular sensors, actuators, drug delivery devices, and others (Penchovsky & Stoilova, 2013). For instance, molecular sensors can detect the presence or the absence of specific molecules and pass predefined molecular signals to other sensors. Such molecular sensors can be used as report systems for many different biosensoring applications including drug discovery through high-throughput screening arrays(Penchovsky, 2013). Moreover, molecular sensors can be engineered to work as Boolean logic gates. As a result, they can perform logical operations and solve computational problems. Molecular logic gates can be designed to work together by passing signals between them in various circuits in vitro(Penchovsky & Breaker, 2005) as well as in vivo.

In fact, nanobiotechnology is one of the fastest growing fields of nano research based on engineering nanosystems using various biomolecules. It refers to the intersection of nanotechnology and biology. This chapter discusses the main applications of designer nanostructures and nanodevices based on DNA (Seeman, 2004) and RNA (Famulok & Ackermann, 2010; Guo, 2010) molecules. In fact, one of the first nanostructures were made of nucleic acids using the expertise accumulated in recombinant DNA technology and molecular biology over the last three decades. Nucleic acids have been proven to be suitable nanoscale materials. They are relatively easy to synthesize, amplify, detect, and modify. They can be used both in vitro and in vivo. Therefore, nucleic acids engineering plays a very important role in modern nanobiotechnology. Nucleic acid-based nanotechnology involves the engineering of various nanostructures based on DNA or RNA molecules.

The progress achieved by the next generation sequencing (NGS) technologies(Mardis, 2008) in recent years led to the discovery of novel targets for drug development and diagnostics. The interplay among RNA engineering, RNA biology, NGS technologies, and medical genomics creates new possibilities for drug development and molecular diagnostics. In this review, I present current and future RNA-based approaches to medical genomics as the focus set on drug development (Penchovsky & Stoilova, 2013), molecular diagnostics (Penchovsky, 2012b) and forthcoming RNA-based therapeutic strategies (Penchovsky, 2012a; Penchovsky & Kostova, 2013).

Key Terms in this Chapter

Ribozymes: Functional RNA molecules that catalyze specific biochemical reactions. They are widely spread in all kingdoms of life.

Allosteric Ribozymes: They are usually engineered ribonucleic acid (Harris et al.) molecules. They can possess various Boolean logic functions, including NOT, YES, OR, AND, and others. They can sense different molecular signals (effectors), including small molecules, RNA and DNA oligonucleotides, polypeptides, and others. The allosteric domain(s), which bind the effector(s), is distant from the catalytic center of the ribozyme.

Computational Design of Allosteric Ribozymes: Fully computerized approaches for obtaining allosteric ribozyme sequences with predefined properties.

Bacterial Riboswitches: RNA molecules, usually residing at the 5’untranlated region (UTR) of mRNAs that control gene expression by directly binding metabolites. They consist of ligand-binding aptamer domain and an expression platform.

RNA Aptamers: These have complex tertiary structures that form pockets for selectively binding a specific ligand. The first aptamers are synthetic RNA molecules obtained by in vitro selection. Later, naturally occurring RNA aptamers are discovered in the gene control elements termed riboswitches (see above).

Apoptosis: Various inducible biochemical pathways that lead to a programed cell death. This process plays an important role in prevention of cancer development.

Gene Therapy: A set of methods for curing different diseases by employing viral vectors.

Exogenous Control of Gene Expression: An engineering approach for a regulation of synthetic genes.

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