The National Cancer Institute, in a joint effort with the National Human Genome Research Institute, has launched a major initiative to develop a Cancer Genome Atlas, an effort that will require the development of faster and less expensive methods for sequencing the human genome. Indeed, investigators are taking a variety of approaches to develop such methods, and if successful, their work could bring the era of personalized, genome-based cancer therapeutics closer to reality.
Now, a paper published in the journal Nano Letters, describes a method to sequence a human genome in a matter of hours, at a potentially low cost, by measuring the electrical perturbations generated by a single strand of DNA as it passes through a nanopore.
“Current DNA sequencing methods are too slow and expensive for it to be realistic to sequence people’s genomes to tailor medical treatments for each individual,” said Massimiliano Di Ventra, Ph.D., of the University of California at San Diego (UCSD), who directed the project. “The practical implementation of our approach could make the dream of personalizing medicine according to a person’s unique genetic makeup a reality.”
Di Ventra and his colleagues used mathematical calculations and computer modeling of the motions and electrical fluctuations of DNA molecules to determine how to distinguish each of the four different bases (A, G, C, T) that constitute a strand of DNA. They based their calculations on a pore about a nanometer in diameter made from silicon nitride – a material that is easy to work with and commonly used in nanostructures – surrounded by two pairs of tiny gold electrodes. The electrodes would record the electrical current perpendicular to the DNA strand as the DNA passed through the pore. Because each DNA base is structurally and chemically different, each base creates its own distinct electronic signature.
Previous attempts to sequence DNA using nanopores were not successful because the twisting and turning of the DNA strand introduced too much noise into the signal being recorded. The new idea takes advantage of the electric field that drives the current perpendicular to the DNA strand to reduce the structural fluctuations of DNA while it moves through the pore, thus minimizing the noise.
The researchers caution that there are still hurdles to overcome because no one has yet made a nanopore with the required configuration of electrodes, but they think it is only a matter of time before someone successfully assembles the device. The nanopore and the electrodes have been made separately, and although it is technically challenging to bring them together, the field is advancing so rapidly that they think it should be possible in the near future.
This work is detailed in a paper titled, “Fast DNA sequencing via transverse electronic transport.” An investigator from the California Institute of Technology also participated in this study. This paper was published online in advance of print publication. An abstract of this paper is available at the journal’s website.