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Nanoscale DNA Sequencing Process Developed

DNA fragment (Wikimedia Commons)

(Wikimedia Commons)

Physicists at University of Washington in Seattle and microbiologists from University of Alabama at Birmingham have developed a sensor with the ability to read the sequence of DNA one strand at a time. A description of their research, with implications for inexpensive DNA sequencing and personalized medicine,  appears in this week’s issue of the journal Nature Biotechnology (paid subscription required).

The team led by Washington’s Jens Gundlach developed the sensor from a benign, natural source. They genetically engineered a protein pore from the Mycobacterium smegmatis, a form of bacteria that forms a biofilm and rarely causes disease, nor is it a parasite that lives off an animal host. The pore in the micro-organism has an opening of one nanometer — one billionth of a meter — just large enough for a single DNA strand to pass through.

To make the sensor, Gundlach’s team placed the protein pore in a membrane surrounded by potassium-chloride solution, with a small voltage to create an ion current flowing through the nanoscale opening. Each type of DNA nucleotide — cytosine, guanine, adenine and thymine — creates a unique electrical signal as it passes through the nanopore. Nucleotides are strings of molecules that make up the structural units of DNA.

The researchers adapted a molecular motor developed in a similar effort at University of California at Santa Cruz. The motor is taken from an enzyme associated with a virus that pulls the DNA strand through the nanopore reader. The motor pulls the strand through the pore at speed of tens of milliseconds per nucleotide, which is considered manageable for reading the electrical signal that is given off when drawn through the nanopore.

Gundlach and colleagues tested their process on six different strands of DNA, each with readable regions 42 to 53 nucleotides. The results, say the authors, correspond to the known DNA sequences of the strands.

“There is a clear path to a workable, easily produced sequencing platform,” notes Gundlach, adding that this method could lead to more affordable personalized medicine, revealing predispositions for afflictions such as cancer, diabetes or addiction.

One of the ways Gundlach says the nanopore technique can help make personalized medicine feasible is when the process is used to identify DNA modifications in a given individual, known as epigenetic DNA modifications. These DNA modifications take place as chemical reactions within cells and are sometimes the underlying causes of various conditions, including cancer.

Read more: Nanotech Helps Reduce Cancer Drug Side Effects

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