The cellular role of DNA is relatively limited, perhaps because of the restrictions imposed by bonding between complementary strands. Outside the cell, however, nanoengineers are uncovering the many hidden talents of DNA. The DNA sequence is able to process information in biochemical assays, its structure is an ideal building material, and its folding pathway allows DNA to move and respond to its environment. Here, I review several innovative applications of designed DNA molecules, some underlying design principles and the prospects for future developments. The applications of new DNA-based technologies range from molecular diagnostics to protein purification and from therapeutics to the assembly of tiny electronic circuits. These uses exploit the properties of DNA at three levels -sequence only, structure (which depends on sequence) and folding pathways (which depend on both sequence and structure) -as the following examples show. By taking their cue from the genetic code found in nature, nanoengineers are now using DNA sequences in vitro to direct the synthesis and evolution of molecules with new functions and reactive properties. When attached to other molecules, detection methods that exploit DNA sequences allow complementary molecules to be identified at extremely low concentrations. DNA sequences can also be used, in a non-biological setting, to control the layout of electronic components in a nanocircuit. DNA strands can fold into stable structures that have valuable functional and material properties. Sensitive methods for detecting DNA have been extended to detect proteins and other macromolecular targets of DNA aptamers -that is, nucleic-acid molecules that have high binding specificity for their targets. Lattices and even three-dimensional (3D) objects have been self-assembled from rigid DNA structures. DNA lattices can organize proteins and nanoelectronic components on a surface with unprecedented precision, making it possible to gain a better understanding of the properties and interactions of proteins. The folding pathway of a DNA molecule to its stable structure allows it to move and perform mechanical functions. The energy released in DNA-folding pathways has been used in vitro to drive motors, providing the ability to release, grab or cleave target molecules and even to control the release of drugs, depending on the outcome of certain diagnostic tests. This review focuses on the recent developments in generating rationally designed DNA molecules and their applications. The past decade has seen huge advances in the development of design principles, particularly by exploiting DNA structure and folding pathways, but also in applications of designed DNA sequences. Together, techniques for the in vitro selection or molecular evolution of DNA molecules from random pools have given spectacular yields, including DNA aptamers and enzymes, which can inhibit the expression of harmful genes or disrupt protein function. Excellent reviews of selected DNA molecules can be found elsewhere 1-3 ; this paper includes only examples of designed DNA molecules, or molecules that combine both selected and designed Abstract | Long admired for its informational role in the cell, DNA is now emerging as an ideal molecule for molecular nanotechnology. Biologists and biochemists have discovered DNA sequences and structures with new functional properties, which are able to prevent the expression of harmful genes or detect macromolecules at low concentrations. Physical and computational scientists can design rigid DNA structures that serve as scaffolds for the organization of matter at the molecular scale, and can build simple DNA-computing devices, diagnostic machines and DNA motors. The integration of biological and engineering advances offers great potential for therapeutic and diagnostic applications, and for nanoscale electronic engineering.
Output: Designed DNA molecules: principles and applications of molecular nanotechnology