Treating
disease has traditionally been a one-size-fits-all endeavor.
Tailoring treatments to an individual’s unique genes is unrealistic
given current DNA sequencing methods: it takes months and millions
of dollars to sequence a human genome.
But a team led by UCSD physicists has developed a technique that
could revolutionize medicine by making it possible to sequence
a human genome in a matter of hours at a potentially low cost. “The practical implementation of our approach could make the dream
of personalizing medicine according to a person’s unique genetic
makeup a reality,” says Massimiliano Di Ventra, an associate
professor of physics at UCSD who directed the study, which was published
in the journal Nano Letters.
Di Ventra and colleagues’ technique involves measuring the
electrical perturbations generated by a single strand of DNA as it
passes through a pore a thousand times smaller than the diameter
of a human hair. Each letter, or base (A, G, C, T), in a DNA sequence
creates its own distinct electronic signature as it moves through
a nanopore. The physicists used mathematical calculations and computer
modeling to determine how to distinguish the different DNA bases.
They based their calculations on a pore 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 recorded the
electrical current perpendicular to the DNA strand as the DNA moved
through the pore. 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. The new idea uses an electric field
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. However, the nanopore and electrodes have been made
separately, and the field is advancing rapidly. In addition to the speed and low cost of the nanopore method,
the researchers calculate that it will be significantly less
error-prone
than current methods. “It should be possible to sequence strands of DNA that are tens of thousands
of base pairs in length, possibly as long as an entire gene, in one pass through
the nanopore,” says Johan Lagerqvist, a graduate student in physics at
UCSD and the lead author on the paper. “With the current method it is necessary
to chop the DNA into smaller pieces, copy the DNA and use multiple sequencing
machines, which introduces additional sources of error.” — Sherry Seethaler
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