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Telomerase

Cells are the building blocks for all tissues in the human body and cell division plays a critical role in the normal growth, maintenance and repair of human tissue. However, in the human body, most cell division is a limited process. Depending on the tissue type, cells generally divide only 60 to 100 times during the course of their normal lifespan.

We and our collaborators have shown that telomeres, located at the ends of chromosomes, are key genetic elements involved in the regulation of the cellular aging process. Our work has shown that each time a normal cell divides, telomeres shorten. Once telomeres reach a certain short length, cell division halts and the cell enters a state known as replicative senescence or aging. Thus, this shortening of the telomeres effectively serves as a molecular "clock" for cellular aging. We and others have shown that when the enzyme telomerase is introduced into normal cells, it can restore telomere length - reset the "clock" - thereby increasing the functional lifespan of the cells. Importantly, it does this without altering the cells' biology or causing them to become cancerous. Human telomerase, a complex enzyme, is composed of a ribonucleic acid (RNA) component, known as hTR, a protein component, known as hTERT, and other accessory proteins. In 1994, we cloned the gene for hTR, and in 1997, with collaborators, cloned the gene for hTERT.

Our work and that of others has shown that telomerase is not present, or is present at very low levels, in most normal cells and tissues, but that during cancer progression, telomerase is abnormally reactivated in all major cancer types. We have shown that while telomerase does not cause cancer (which is caused by mutations in oncogenes and tumor suppressor genes), the continued presence of telomerase enables cancer cells to maintain telomere length, providing them with indefinite replicative capacity. We and others have shown in various tumor models that inhibiting telomerase activity results in telomere shortening and causes aging or death of the cancer cell.

Although telomerase is expressed in nearly all cancer cells, it is not expressed in most normal cells. That gives telomerase the potential of being both a universal as well as a highly specific cancer target. This specificity means that drugs and biologics that attack cancer cells by targeting telomerase may leave other cells unaffected, and thus should have fewer side effects than conventional chemotherapeutic agents that typically attack both cancer and non-cancer cells.

We are developing anti-cancer therapies based on telomerase inhibitors, telomerase therapeutic vaccines and, through a licensee, telomerase-based oncolytic (cancer-killing) viruses. Through our licensees, we also intend to develop products using telomerase as a marker for cancer diagnosis, prognosis, patient monitoring and screening.

We are also researching compounds that transiently activate telomerase in senescent cells to restore cell function for treatment of injuries and chronic diseases.

Following is a list of telomerase-related products that we are developing. Click on the links below for more information about a specific product.

Product Product Description Disease Treatment Development Stage
GRN163L Telomerase Inhibitor Chronic Lymphoproliferative Disease Phase I/II Trial
GRN163L Telomerase Inhibitor Solid Tumors Phase I Trial
GRN163L Telomerase Inhibitor Non-Small Cell
Lung Cancer
Phase I/II Trial
GRN163L Telomerase Inhibitor Multiple Myeloma Phase I/II Trial
GRN163L Telomerase Inhibitor Breast Cancer Phase I/II Trial
GRNVAC1 Telomerase Cancer Vaccine Acute Myelogenous Leukemia (AML) Phase II Trial
Visionary Therapeutics
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