Fast Track DNA

Imagine a world in which your doctor had a complete readout of your DNA — all the three billion base pairs that help make you unique. The doctor could scan your genome for the genes associated with certain disease risks or severe drug side effects and could then design your treatment accordingly. 

Very few doctors and patients currently have the time or money for such personalized medicine. Sequencing an individual’s entire genome requires repeated biochemical steps, including snipping DNA strands into thousands of pieces, amplifying them, and then fragmenting them again, before piecing it all back together via computer. The process can take months, and according to the National Institutes of Health (NIH), costs around $10 million.

The solution — a much cheaper and faster means of sequencing genomes — could come from Boston University. Last month, Amit Meller and Zhiping Weng, College of Engineering associate professors of biomedical engineering, won a $2.2 million, three-year grant from the NIH’s National Human Genome Research Institute to pursue DNA sequencing with nanopores, one of about 30 projects the NIH is funding nationwide in its quest for a “$1,000 genome.”

“It became clear that if we can reduce the amount of genetic material and biological reagents needed for sequencing, we could remove most of the time and cost of amplification,” says Meller.

Indeed, only a few copies of DNA would be needed for the nanopore sequencing technique Meller and Weng are developing. The method would use an electric current to pull segments of a single DNA strand through an array of holes in a thin silicon membrane, holes so tiny that just one link of DNA could fit through at a time. Fluorescent tags attached to each base pair would allow an optical sensor to read the DNA sequence in order as the segments pass through the membrane. The hope, says Meller, is that this nanopore technology could allow scientists to sequence an entire human genome in a matter of a few hours.

In addition to enhancing individualized medicine, readily available genome sequences would give scientists a powerful tool in the study of disease, according to Jeffrey Schloss, program director for technology development at the National Human Genome Research Institute. It would allow researchers to know the full genome of thousands of patients in a study looking for genetic links with various diseases. At present, genetics research can look only for correlations between a large number of specific genetic variants and disease, but “complex diseases are caused by multiple genes, and often each gene only makes a small difference,” says Schloss. In addition, today’s population-based studies can’t detect rearranged or repeated segments in a genome and rearrangements are believed to have significant health effects.

Meller and Weng have yet to sequence any DNA using their technique, but with the NIH support, they anticipate rapid progress in 2007. Currently, they are designing a custom microscope capable of the superfast optical imaging and atomic precision necessary to accurately read the DNA segments as they speed through the nanopores at about 500 nucleotides per second. Weng will develop the computational component of the process, code that a cluster of computers will use to read the gigabytes of data that the sensors produce and patch them together into a fully sequenced genome. In addition, the duo have so far produced membranes with 36 nanopores each, when ideally they would like to have around 2,500 nanopores or more per array for higher throughput speed.

“We have all the basic technologies in our hands,” says Meller. “We just need to combine all these components into a working setup. And that’s the real challenge now.”

Chris Berdik can be reached at cberdik@bu.edu.