Recently Cloned Gene Produces Telomerase Activity in Normal Human Cells

Geron Corporation announced in Nature Genetics that it has, for the first time, produced telomerase activity in normal, mortal human cells using the recently cloned gene for the human telomerase catalytic protein.

Telomerase is a rarely expressed enzyme believed to play a key role in the regulation of cell lifespan, functioning as part of a molecular clock of cell aging. Its absence imparts mortality to some cells and its presence imparts replicative immortality to others.

“Reconstituting telomerase activity, especially in normal human cells, is a major milestone in telomerase biology that has widespread implications for the treatment of cancer and age-related diseases,” said Jerry Shay, PhD, professor of cell biology at the University of Texas Southwestern Medical Center at Dallas, and a coauthor of the paper.

Enzyme Produced

In the September 1, 1995, issue of Science, Geron scientists and their collaborators at Cold Spring Harbor Laboratory were the first to announce the cloning of the RNA component (“hTR”) of human telomerase. On August 15, 1997, again in Science, Geron and collaborators at the University of Colorado reported the cloning of the critical or catalytic protein component (“hTRT”) of human telomerase.

“We have demonstrated that for the first time telomerase activity can be generated in normal human cells using recombinant telomerase. Further, having discovered the two key components that are responsible for telomerase activity (hTRT and hTR), we are now in a stronger position to identify chemical compounds that regulate the activity of the enzyme,” said Calvin Harley, PhD, Geron’s chief scientific officer.

New Tool in Cancer Treatment?

Because telomerase is required for the proliferation of cancer, work is being done to discover anticancer drugs that can inhibit telomerase. Such drugs are expected to lead to the death of cancer cells through resumed telomere shortening, with little to no effect expected on normal cells and tissues. Telomerase has previously been shown to be active in all types of cancer examined and not expressed in most normal tissues. Telomerase is therefore thought to be unique among anticancer targets for its universality and specificity to cancer cells.

Coauthors of the Nature Genetics article include Rebecca Taylor and Drs. Scott L Weinrich, Ron Pruzan, Libin Ma, Andrea G. Bodnar, Serge Lichtsteiner, Nam W. Kim, James B. Trager, Ruben Carlos, William H. Andrews, and Gregg B. Morin, all from Geron; as well as Drs. Michel Ouellette, Valerie M. Tesmer, Shawn E. Holt and Woodring E. Wright, all from the University of Texas Southwestern Medical Center at Dallas.