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As efforts such as The Cancer Genome Atlas and others generate vast quantities of information about the genetic makeup of different types of cancer, it is becoming increasingly clear that such information has great potential for determining which anticancer drugs should be used to treat a specific patient. However, realizing that potential will require not only that cancer researchers uncover the links between specific gene changes in a given tumor and that tumor's response to a specific drug therapy, but that technologists develop faster methods of detecting specific mutations that would be economical to use on individual patients.
A technological breakthrough to address this latter issue may be at hand thanks to recent work conducted by Amit Meller and his colleagues at Boston University. Reporting their work in the journal Nano Letters, these investigators described the use of electrically charged nanopores to detect specific genetic sequences as single DNA molecules pass through the pore. If further development proves successful, this method could yield a new approach to mutation detection that does not involve time-consuming and expensive amplification processes.
The investigators built their sequencing device by using a focused electron beam to drill a 4-5 nanometer diameter hole in a silicon nitride membrane. The membrane is then placed between two small fluid chambers and an electric field is applied across the membrane using a pair of silver/silver chloride electrodes. This applied current causes individual DNA molecules to move through the pore, untwisting and unraveling as they enter the pore.
In order to identify a known genetic sequence, the investigators first treat a DNA sample with specific sequences of a DNA analog known as a peptide nucleic acid, or PNA, that will bind to the proper complementary DNA sequence of interest. When the matched DNA-PNA sequence passes through the pore, it produces a marked change in the electrical current passing between the two electrodes, a change that the investigators demonstrated is easily distinguished from unaltered double-stranded DNA, that is, DNA not duplexed with the PNA probe. The device is capable of analyzing one DNA molecule per second.
This work is detailed in a paper titled "Nanopore Based Sequence Specific Detection of Duplex DNA for Genomic Profiling." An abstract of this paper is available at the journal's Web site.
About NCI Alliance for Nanotechnology in Cancer
To help meet the goal of reducing the burden of cancer, the National Cancer Institute (NCI), part of the National Institutes of Health, is engaged in efforts to harness the power of nanotechnology to radically change the way we diagnose, treat and prevent cancer.
The NCI Alliance for Nanotechnology in Cancer is a comprehensive, systematized initiative encompassing the public and private sectors, designed to accelerate the application of the best capabilities of nanotechnology to cancer.
Currently, scientists are limited in their ability to turn promising molecular discoveries into benefits for cancer patients. Nanotechnology can provide the technical power and tools that will enable those developing new diagnostics, therapeutics, and preventives to keep pace with today’s explosion in knowledge.
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