DNA Nanotechnology 2.5

editorial DNA nanotechnology 2.5

For DNA nanodevices to be deployed in living cells and higher organisms, they need to be biocompatible and inexpensive enough to be produced in large quantities.

Deoxyribonucleic acid (DNA) — the or even perform logic functions like a better understand how these structures molecule that carries the genetic computer. Furthermore, it is expected that distribute and move around the body, and information of a living organism — is the programmability of DNA could resolve how the body’s immune system reacts diverse in structure and function. The the long-standing issue of selectivity in to their presence. Although DNA is a components that make up DNA (the drug targeting and delivery. Ultimately, natural biopolymer, organisms have very nucleobases) snap together in very specific these devices would be able to interact sophisticated mechanisms to detect and ways through hydrogen bonding. In with the cell, and/or emulate the missing eliminate foreign or unnatural DNA in nature, this complementary base-pairing components of a complex biological order to protect their own DNA. It is much contributes to DNA’s helical structure system. In a Review article in this issue, like a response to a viral infection: in the and the way genetic information is stored Georg Seelig and colleagues examine presence of foreign DNA, cells upregulate and retrieved. Biologists have long used some of these applications and outline certain genes and stimulate the release the circularized form of DNA (known as the key issues that need to be resolved of cytokines that have antimicrobial or plasmids) to carry genes into bacterial cells before DNA nanostructures can emerge inflammatory properties. For DNA-based for cloning and amplification. Because as a competitive alternative drug delivery vaccines, this feature is useful for boosting of its programmability, DNA has also technology, and a unique therapeutic the immune system. However, in other earned itself a reputation as a versatile and/or diagnostic material4. cases, chronic expression of these genes engineering material. In the last 30 years, and inflammatory responses can be very the DNA nanotechnology community has Organisms have sophisticated damaging. In a Perspective article in this gone from an initial wave of making static issue, Yamuna Krishnan and co-workers structures of different shapes and sizes, mechanisms to detect and outline the anticipated molecular, cellular to a second wave of creating increasingly eliminate foreign DNA to and organismal pathways that DNA sophisticated and dynamic structures nanodevices will encounter when they are capable of carrying drugs, interacting protect their own DNA. introduced into higher organisms5. The with cell surface proteins and performing choice is designing DNA nanostructures certain functions inside cells1,2. At the same The first step in making the leap to either evade or interact with the body’s time though, significant developments in from well-controlled cell-free settings surveillance system. the design of static DNA nanostructures to complex cellular environments, and Although it is believed that DNA continue to be made, as illustrated, for then on to higher organisms, is to resolve nanodevices have considerable potential example, by Hao Yan and colleagues in this issues surrounding the stability of these as drug delivery vehicles, the community issue3. In the near future, as researchers DNA nanostructures. The inside of a should carefully consider exactly how the look to move DNA nanodevices from cells cell is complex and crowded — DNA programmability of DNA can be exploited and into higher organisms, there is plenty nanodevices will struggle to diffuse to create a conceptually new type of drug to consider. through the complex cytoplasmic delivery device. Recent advances in DNA DNA nanodevices are constructed by mixture, and will need to fend off nanotechnology have provided a rich either tiling together the sticky ends of DNA-binding proteins and enzymes toolbox for engineering living organisms different DNA motifs (a method called that break them down. Furthermore, and building molecular logic circuits. With DNA tiling), or by folding a long single- most DNA nanostructures (with the the help of such capabilities, drug delivery stranded DNA scaffold into a desired exception of the DNA icosahedron and vehicles or approaches can be envisaged to structure with the help of short staple tetrahedron) require high concentrations offer something more sophisticated than the strands (which is known as DNA origami). of divalent cations, such as magnesium injection of a static container, as practiced In the case of dynamic structures, such ions, to assemble. Because physiological today. For this to become a reality, the cost as those that can move or perform concentrations of magnesium ions are of producing high-quality DNA, which has computational tasks, strand displacement considerably lower, the nanostructures decreased in recent years, will first have to is used, whereby the nanodevice is fall apart; stability can be achieved become competitive with that of producing programed to respond to an incoming through the addition of salt, the protein antibodies and polymers6. ❐ DNA strand that displaces an existing one actin, or magnesium ions. Importantly, on the nanodevice. more studies are needed to understand References The ability to program these structures how stability can be programmed 1. Jones, M. R., Seeman, N. R. & Mirkin, C. Science to fold a certain way, carry information into the DNA nanostructures, rather 347, 1260901 (2015). and reconfigure themselves means that than attained through manipulating 2. Pinheiro, A. V., Han, D., Shih, W. M. & Yan, H. Nature Nanotech. 6, 763–772 (2011). DNA nanodevices can be designed to do environmental conditions. 3. Zhang, F. et al. Nature Nanotech. 10, 779–784 (2015). many things. They can, for example, carry As more DNA nanostructures are 4. Chen, Y-J., Groves, B., Muscat, R. A. & Seelig, G. Nature Nanotech. drugs and deliver them to targets in clever injected through different routes into 10, 748–760 (2015). 5. Surana, S., Shenoy, A. R. & Krishnan, Y. Nature Nanotech. ways, or can be designed to have movable higher organisms for various applications, 10, 741–747 (2015). parts that can sense and/or amplify signals, it is becoming increasingly important to 6. Carlson, R. Nat. Biotechnol. 27, 1091–1094 (2009).

NATURE NANOTECHNOLOGY | VOL 10 | SEPTEMBER 2015 | www.nature.com/naturenanotechnology 729