DNA-incorporating nanomaterials in biotechnological applications In the past 25 years, the utility of DNA has expanded well beyond its biological context as the storage mechanism of genetic informa- tion, and has become widely used in the arena of nanoscale construction [1,2] . DNA is well- suited for biomolecular directed design of nano- structures because of its physical and chemical stability, and ability to tolerate a variety of modi- fcations compared with other biomolecules, such as proteins [1,2] . Unlike proteins, where molecular recognition is governed by a number of complex factors, DNA hybridization based upon strand complementarity is programmable and predictable [2,3] , while its nonspecifc inter- actions can be understood on a basis of polymer concepts. The power and versatility of supra- molecular constructs based on DNA motifs to fabricate well-defned geometric shapes beyond the double helix was pioneered by Seeman and coworkers, and continues to be demonstrated by a number of prominent researchers [4–7] . In addi- tion, the in vitro selection of functional nucleic acids with a broad range of af fnities, known as aptamers, has diversifed the sensor applications of nucleic acids in the biomedical feld. Aptamers can be selected for a wide array of targets, rang- ing from metal ions to whole cells, and can be readily synthesized and modifed to improve their function, similar to hybridization-based nucleic acid probes [2,8] . Advancements in the fabrication of nanopar- ticles that incorporate DNA motifs and methods for their characterization have led to the develop- ment of a broad range of biodiagnostic and ther- apeutic platforms [9] . The use of nanoparticles in molecular recognition applications has been fueled by the ever-increasing assortment of nano-objects of various shapes, sizes, composi- tions and functionalities [1] . Nanoparticles, par- ticularly metallic and semiconducting, exhibit unique optical, electronic, magnetic and cata- lytic properties and are highly sensitive to per- turbations in their local environment [1,8] . For biomedical applications, DNA-functionalized nanoparticles are appealing because nano- particles are similar in size to DNA and subtle changes in DNA structure typically lead to sig- nifcant changes in the nanoparticle’s physical properties [1,2] . The large ratio of nanoparticle surface area to a footprint of anchored DNA allows for creation of localized volumes with high DNA concentrations, which makes local DNA molecular recognition more effective, but also leads to a deviation of properties of DNAs The recently developed ability to controllably connect biological and inorganic objects on a molecular scale opens a new page in biomimetic methods with potential applications in biodetection, tissue engineering, targeted therapeutics and drug/gene delivery. Particularly in the biodetection arena, a rapid development of new platforms has largely been stimulated by a spectrum of novel nanomaterials with physical properties that offer ef fcient, sensitive and inexpensive molecular sensing. Recently, DNA- functionalized nano-objects have emerged as a new class of nanomaterials that can be controllably assembled in predesigned structures. Such DNA-based nanoscale structures might provide a new detection paradigm due to their regulated optical, electrical and magnetic responses, chemical heterogeneity and high local biomolecular concentration. The specifc biorecognition DNA and its physical–chemical characteristics allows for an exploitation of DNA-functionalized nanomaterials for sensing of nucleic acids, while a broad tunability of DNA interactions permits extending their use for detection of proteins, small molecules and ions. We discuss the progress that was achieved in the last decade in the exploration of new detection methods based on DNA-incorporating nanomaterials as well as their applications to gene delivery. The comparison between various detection platforms, their sensitivity and selectivity, and specifc applications are reviewed. KEYWORDS: assembly n detection n DNA n gene delivery n nanoparticle functionalization n nanoparticles n optical sensing Andrea Stadler 1 , Cheng Chi 2 , Daniel van der Lelie 1 & Oleg Gang 2† † Author for correspondence: 1 Biology Department, Brookhaven Natonal Laboratory, Upton, New York 11973, NY, USA ogang@bnl.gov 2 Center for Functonal Nanomaterials, Brookhaven Natonal Laboratory, Upton, New York 11973, NY, USA 319 Review ISSN 1743-5889 10.2217/NNM.09.02 © 2010 Future Medicine Ltd Nanomedicine (2010) 5(2), 319–334 For reprint orders, please contact: reprints@futuremedicine.com