Speeding up DNA identification - Univ of Texas Southwestern Medical Center researchers alter oligonucleotide probes for faster identification of DNA sequences - Brief Article

USA Today (Society for the Advancement of Education), June, 1997

Scientists at University of Texas Southwestern Medical Center at Dallas have shown that genetic probes can be modified to accelerate recognition of DNA sequences and increase the strength of their binding. The probes, known as oligonucleotides, are short man-made pieces of DNA-like molecules. Engineering improvements in their properties could make clinical testing for inherited diseases faster, suggests David Corey, assistant professor of pharmacology and Howard Hughes Medical Institute assistant investigator.

DNA is negatively charged and will repel unmodified DNA-based gene probes because they are, too. This limits the ability of probes to recognize DNA sequences within genes rapidly. To avoid this, the researchers used oligonucleotides stripped of their negative charge or which had a positive charge attached. These neutral molecules were not repelled by DNA while searching for a matching sequence, allowing them to bind faster and more tightly.

Such altered oligonucleotides should facilitate identification of genetic changes that determine an individual's inherited traits and diseases, Corey indicates. "DNA recognition is important for diagnosing genetic diseases because those are caused by a change in the DNA. You bring in a small piece of DNA to find out if a change is actually there or not. In the next 10 years, in the average doctor's office, physicians will be able to test people for a whole range of genetic diseases. That will be done by oligonucleotides recognizing complementary sequences.

"What we've shown is that you can manipulate the charge on the probe to increase the speed at which you can identify genes." This means current methods of gene identification would take an hour to accomplish what modified oligonucleotides would do in 30 seconds. In addition, it takes less DNA for the test, and the sample will last longer because it can't be changed by enzymes.

"On the diagnostic side of genetic testing, this is a very important tool. On the therapeutic side, it's been a great dream of a lot of scientists to develop a magic bullet that can target any gene. That would be wonderful. Oligonucleotides offer that possibility because they can, in theory, recognize any sequence. But that has been impossible because the chemical makeup hasn't been favorable. Everything I've seen says that the neutral oligonucleotides can target specific genes. Once scientists know how to get them into cells, we'll be able to ask the important question: `How well do they turn genes on or off?'"