Scientists at Arizona State University's Biodesign Institute have developed the world's first gene detection platform made up entirely from self-assembled DNA nanostructures.
The results, appearing in the January 11 issue of the journal Science, could have broad implications for gene chip technology and may also revolutionize the way in which gene expression is analyzed in a single cell.
“We are starting with the most well-known structure in biology, DNA, and applying it as a nano-scale building material, ” said Hao Yan, a member of the institute's Center for Single Molecule Biophysics and an assistant professor of chemistry and biochemistry in the College of Liberal and Sciences.
Yan is a researcher in the fast-moving field known as structural DNA nanotechnology — that assembles the molecule of life into a variety of nanostructures with a broad range of applications from human health to nanoelectronics.
Yan led an interdisciplinary ASU team to develop a way to use structural DNA nanotechnology to target the chemical messengers of genes, called RNA.
The team included: lead author and chemistry and biochemistry graduate student Yonggang Ke; assistant professor of chemistry and biochemistry Yan Liu; Center for Single Molecule Biophysics director and physics professor Stuart Lindsay; and associate professor in the School of Life Sciences, Yung Chang.
"This is one of the first practical applications of a powerful technology, that, till now, has mainly been the subject of research demonstrations,” said Lindsay. “The field of structural DNA nanotechnology has recently seen much exciting progress from constructing geometrical and topological nanostructures through tile based DNA self-assembly initially demonstrated by Ned Seeman, Erik Winfree and colleagues,” said Yan.
A recent breakthrough of making spatially addressable DNA nanoarrays came from Paul Rothemund's work on scaffolded DNA origami, a method in which a long, single-stranded viral DNA scaffold can be folded and stapled by a large number of short synthetic “helper strands” into nanostructures that display complex patterns.
“But the potential of structural DNA nanotechnology in biological applications has been underestimated, and if we look at the process of DNA self-assembly, you will be amazed that trillions of DNA nanostructures can form simultaneously in a solution of few microliters, and very importantly, they are biocompatible and water soluble,” said Yan.
DNA chip and microarray technology have become a multi-billion dollar industry as scientists use it to examine thousands of genes at the same time for mutations or uncovering clues to disease. However, because DNA probes are pinned to the solid surface of the microarray chips, it is relatively slow process for the targets to search and find the probes. Also, it is hard to control the distances between the probes with nanometer accuracy.
“In this work, we developed a water soluble nanoarray that can take advantage of the DNA self-assembling process and also have benefits that the macroscopic DNA microchip arrays do not have,” said Yan. “The arrays themselves are reagents, instead of solid surface chips.”
To make the DNA origami RNA probes, Yan has taken advantage of the basic DNA pairing rules in the DNA chemical alphabet (“A” can only form a zipper-like chemical bond with “T” and “G” only pair with “C”). By controlling the exact position and location of the chemical bases within a synthetic replica of DNA, Yan programmed a single stranded genomic DNA, M13, into nanotiles to contain the probes for specific gene expression targets.