UT Southwestern Researchers Find Way To Control Gene Activity, Opening Way For Cancer Drugs

DALLAS - May 12, 1999 - Researchers at UT Southwestern Medical Center at Dallas have developed a method to turn off a gene for telomerase, which activates the continuous division of cancer cells. This finding could aid in the creation of new cancer drugs.

The research team invented a novel method for slipping a small molecule, known as peptide nucleic acid (PNA), into cells, where it then blocked telomerase activity. Telomerase is an enzyme that prevents depletion of the ends -- telomeres -- of chromosomes and allows continuous cell division. The study was reported in the June issue of Chemistry and Biology published today.

Telomeres shorten each time the cell divides, 50 to 70 times during the lifetime of a normal cell. Once the protective tips of DNA are gone, the cells die. All human cells have a gene for telomerase, but it is switched off in normal cells, except embryonic cells, so the enzyme is not manufactured. It is switched on in tumor cells allowing them to divide uncontrollably and be immortal.

The same investigators published a related paper describing the rules for attacking DNA targets with PNAs. That study appeared in March in the Journal of the American Chemical Society.

"A challenge that researchers have faced in trying to switch genes on and off with any efficiency is to identify a small molecule that can enter cells, bind to a target gene and turn the gene off," said Dr. David Corey, co-author of the study, associate professor of pharmacology and biochemistry and a Howard Hughes Medical Institute (HHMI) investigator. "We have a simple way to get PNAs into cells, and we have determined rules guiding their ability to block DNA and RNA targets."

The scientists introduced PNAs into cells by adding a lipid -- a fat-soluble substance. This method allowed delivery of PNAs into the nucleus in almost 100 percent of the tests on two different cell lines, Corey said.

One of the most significant aspects of the work, especially in r

Contact: Susan Steeves
UT Southwestern Medical Center

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