2003 July 08 Tuesday
Progress Toward $1000 Per Person DNA Sequencing

The Scientist has a good review of all the approaches being pursued to dramatically lower the cost of complete genome sequencing. (free registration required)

Some companies estimate that within the next five years, technical advances could drop the cost of sequencing the human genome low enough to make the "thousand-dollar genome" a reality. Whether or not that happens, new sequencing approaches could in the short term facilitate large-scale decoding of smaller genomes. In the long term, low-cost, rapid human genome sequencing could become a routine, in-office diagnostic test--the first step on the road to truly personalized medicine.

Companies discussed in the article which are pursuing approaches to radically lower the cost of DNA sequencing include VisiGen Biotechnologies, 454 Life Sciences, Solexa, and US Genomics. A number of university research labs are also pursuing approaches that may radically lower the cost of DNA sequencing including that of Daniel Branton at Harvard (using nanopores), George Church at Harvard (particularly his work on polymerase colony or polony technology) and Watt W. Webb of Cornell.

The approach being pursued by Cornell professor of applied and engineering physics Watt Webb's group is particularly interesting because the ability to optically watch the behavior a single biomolecule at a time could be used for many research purposes.

His report on watching individual molecules at work, "Zero-Mode Waveguides for Single-Molecule Analysis at High Concentrations," appears in the Jan. 31 issue of the journal Science. The article, which is illustrated on the cover of Science, also is authored by a multidisciplinary group of Cornell researchers: Michael Levene, an optics specialist and postdoctoral associate in applied and engineering physics; Jonas Korlach, a biologist who is a graduate student in biochemistry, molecular and cell biology; former postdoctoral associate Stephen Turner, now president and chief scientific officer of Nanofluidics, a Cornell spin-off (read the story); Mathieu Foquet, a graduate student in applied and engineering physics; and Harold Craighead, professor of applied and engineering physics.

"This is an example of the possibilities provided by integrating nanostructures with biomolecules," said Craighead, the C.W. Lake Jr. Professor of Productivity, who also is co-director of the National Science Foundation (NSF)-funded Nanobiotechnology Center at Cornell. "It represents a major step in the ability to isolate a single active biomolecule for study. This can be extended to other biological systems."

More on Webb's approach.

A new technique for the determination of the sequence of a single nucleic acid molecule is being developed in our laboratory. In its principle, the activity of a nucleic acid polymerizing enzyme on the template nucleic acid molecule to be sequenced is followed in real time. The sequence is deduced by identifying which base is being incorporated into the growing complementary strand of the target nucleic acid by the catalytic activity of the polymerase at each step in the sequence of base additions. Recognition of the time sequence of base additions is achieved by detecting fluorescence from appropriately labeled nucleotide analogs as they are incorporated into the growing nucleic acid strand.

Because efficient DNA synthesis occurs only at substrate concentrations much higher than the pico- or nanomolar regime typically required for single molecule analysis, zero-mode waveguide nanostructures have be developed as a way to overcome this limitation. They effectively reduce the observation volume to tens of zeptoliters, thereby enabling an inversely proportional increase in the upper limit of fluorophore concentration amenable to single molecule detection. Zero-mode waveguides thus extend the range of biochemical reactions that can be studied on a single molecule level into the micromolar range.

The cost of DNA sequencing looks set to drop dramatically. The big question is just how fast will the costs drop. DNA sequencing still costs several million per person. But that is orders of magnitude cheaper than it was 10 years ago. The newer approaches that attempt to read a single strand of molecules could be made very cheap if only they can be made to work in the first place.

See also my previous posts on approaches to lower DNA sequence costs in the Biotech Advance Rates archive.

By Randall Parker at 2003 July 08 11:08 AM 
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test.

Posted by: Randall Parker on March 23, 2006 01:44 PM
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