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Sequencing One Human's Genome In Less Than 24 Hours

What took hundreds of researchers working together for nearly 10 years to complete soon may be accomplished in less than a day.

This is the view of University of Houston researchers who have filed a patent on a new process to sequence the human genome.

Biochemist Susan Hardin and four UH colleagues are developing a new technology for direct molecular sensing that could be used to sequence an individual's entire genome -- the gathering of all the genetic information contained in a person's DNA -- in less than 24 hours.

When fully developed as a commercial device, the technology could offer doctors a more rapid and more thorough way to determine who is at risk for certain genetic diseases, or which people might react adversely to a particular drug.

The technology also could be used to rapidly identify unknown pathogens used in a bioterrorism attack, where quick answers about an organism could save lives.

While the development of the technology is progressing quickly, Hardin estimates that a commercial device based on the direct molecular sensor is about three to five years away. She and colleagues in the UH Department of Biology and Biochemistry -- James Briggs, Xiaolian Gao, David Tu and Richard Willson -- formed a Houston company called Visigen Biotechnologies in 2000 to develop and commercialize the process.

In addition to recent patent applications, Hardin presented information about the technology for the first time Feb. 21 in Miami at the DARPA Tissue Based Biosensors, Advanced Diagnostics and Advanced Detection Technology Program Review.

"If you started today, using current technology to sequence one person's entire genome, the process might take two to four years," says Hardin, an assistant professor of biology and biochemistry at the University of Houston. "That's thanks to technological advances developed in the 10 years it took to complete the Human Genome Project.

"We predict the process we're developing could sequence the human genome in less than a day, and ultimately maybe even less than an hour. I'm hopeful that in a few years we'll be able to do this," she says.

Within each living cell are long strands of DNA, the genetic code containing all the information to create and control every cell in an organism. DNA resembles a long spiraling ladder, and the rungs of the ladder are made up of chemical units called bases. Clusters of bases make up our genes, which determine inherited physical traits and many of our behaviors. Sequencing all this genetic information -- the genome -- requires identifying and determining the order of the billions of bases that make up DNA and individual genes.

The process that Hardin and her colleagues pioneered includes genetically engineering an enzyme called a DNA polymerase, which in current sequencing methods is responsible for moving along a strand of DNA and copying the bases so that they can then be "read" by a computer. Typically this sequencing process is time consuming, taking weeks or months to complete, requires a large number of DNA molecules, and involves many labor-intensive steps.

"We have made our polymerase so that theoretically it should act as a direct molecular sensor, sending a computer a signal telling us immediately the identity of the base it just read," Hardin says. "And that's something we just don't have now. This process would eliminate many time-consuming intermediary steps, and in addition, would require the use of only a single molecule of DNA to 'read'."

Having quick and easy access to a person's entire genetic information opens the possibility for tailoring medical treatments or prevention strategies based on a person's unique genetic makeup.

"There are several genetic diseases that can be aggravated by diet or environment," Hardin says. "If you knew early on, from infancy, perhaps, that you carried the gene for such a disease, then you could take preventive action. You may be able to avoid drug therapy altogether simply by manipulating diet."

For those conditions that do require drug therapy, knowledge of a person's individual genome could lead to more effective treatments, again based on a person's unique reaction to certain pharmaceuticals.

"Pharmaceutical companies have lots of drugs on their shelves that would be great for 90 percent of the population, but which have had really bad side effects in the other 10 percent, based on their DNA. The ability to scrutinize the genes of individual patients would financially benefit the drug companies because they could safely bring those products to market, while also helping people who could truly benefit from those therapies."

Hardin's and Visigen's research efforts are funded in part by the National Institutes of Health and the Defense Advanced Research Programs Agency (DARPA). The DARPA program they are funded through is called the Advanced Diagnostics Program.

"This technology has applications for very rapid and sensitive pathogen identification, so after September 11 our project took on a different tone and sense of urgency," Hardin says. "Just as with human genetic information, if you know the genetic potential of an organism, you can determine how nasty it might be. Also, a complete genetic analysis would be better than a fingerprint in helping to track a pathogen's origin." - By Amanda Siegfried

[Contact: Amanda Siegfried ]






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