Thursday, April 17, 2008

The $100 Genome

Forget the $1,000 genome. Some companies are looking far past that goal to create a really inexpensive sequencing technology.

By Emily Singer

Cheap sequence: Threading long DNA molecules through nano-sized channels on a specially fabricated chip could provide a cheaper way to sequence DNA. This image shows a wafer developed by BioNanomatrix. Each rectangle is a nanoanalyzer chip lined with 50,000 channels. Credit: BioNanomatrix

It currently costs roughly $60,000 to sequence a human genome, and a handful of research groups are hoping to achieve a $1,000 genome within the next three years. But two companies, Complete Genomics and BioNanomatrix, are collaborating to create a novel approach that would sequence your genome for less than the price of a nice pair of jeans--and the technology could read the complete genome in a single workday. "It would have been absolutely impossible to think about this project 10 years ago," says Radoje Drmanac, chief scientific officer at Complete Genomics, which is based in Mountain View, CA.

The most recent figures for sequencing a human genome are $60,000 in about six weeks, as reported by Applied Biosystems last month. (That's down from $3 billion for the Human Genome Project, which was sequenced using traditional methods and finished in 2003, and about $1 million for James Watson's genome, sequenced using a newer, high-throughput approach and released last year.) But scientists are still racing to develop methods that are fast and cheap enough to allow everyone to get their genomes sequenced, thus truly ushering in the era of personalized medicine.

Most existing technologies detect the sequence of DNA a single letter at a time. But Complete Genomics aims to speed the process by detecting entire "words," each composed of five DNA letters. Drmanac likens the technology to Google searches, which query a database of text with keywords. Further speeding up the process with novel chemistry and advances in nanofabrication, the companies will develop a device that can simultaneously read the sequence of multiple genomes on a single chip.

To accomplish the new sequencing, scientists first generate all possible combinations of five-letter DNA segments, given the four letters, or bases, that make up all DNA. These segments are labeled with different types of fluorescent markers and added in groups to a single-stranded molecule of DNA. When a particular segment matches a sequence on the strand of DNA to be read, it binds to that part of the molecule. A specialized camera then snaps a picture--the different fluorescent signals indicate the sequence at specific points along the strand of DNA. The process is repeated with different five-letter DNA combinations, until the entire chromosome is sequenced. The approach is feasible because of the recent availability of cheap DNA synthesis, making it much more efficient to generate libraries of these DNA segments.

Each DNA molecule will be threaded into a nanofluidics device, made by Philadelphia-based BioNanomatrix, lined with rows of tiny channels. The narrow width of the channels--about 100 nanometers--forces the normally tangled DNA to unwind, lining up like a train in a long tunnel and giving researchers a clear view of the molecule. "Since we can stretch out DNA, we can get a huge amount of information from each piece of DNA we look at," says Mike Boyce-Jacino, chief executive officer of BioNanomatrix. "The big difference from any other approach is that we are looking at physical location at the same time we are looking at sequence information." Sequencing methods currently in use sequence small fragments of DNA and then piece together the location of each fragment computationally, which is more time consuming and requires repetitive sequencing.