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Telomerase, an enzyme that prevents chromosomes from shortening when they divide, is widely suspected of playing a key role in making cancer cells immortal. Though researchers have developed a variety of methods for measuring the activity of this enzyme, none of these methods have proved suitable for use in diagnostic assays for cancer or in efforts to develop drugs that block telomerase activity. Now, a team of investigators at Northwestern University's Nanomaterials for Cancer Diagnostics and Therapeutics has developed a new type of nanoparticle-based assay that appears to be both accurate and sensitive enough for clinical use.
Chad Mirkin, Ph.D., principal investigator of the National Cancer Institute-supported Center for Cancer Nanotechnology Excellence at Northwestern, led the research team that developed the new assay. Their results appear in the Journal of the American Chemical Society.
The assay system consists of gold nanoparticles coated with short stretches of DNA that can serve as a substrate for telomerase. When a sample containing this enzyme is mixed with these nanoparticles, telomerase binds to the DNA sequences and begins adding repeated stretches of six specific nucleotides to the end of the DNA. After a short time, the investigators wash off any telomerase and then add magnetic microparticles coated with a piece of oligonucleotide that is complementary to the sequence added by telomerase. The coated magnetic microparticles bind to any elongated DNA and enable the researchers to separate those complexes from the rest of the gold nanoparticles by using a magnetic field. Next, the DNA sequences are removed from the gold nanoparticles and are detected using a silver development process and automated reader that Dr. Mirkin's team invented for a related assay system, known as the biobarcode assay.
Using this assay, the investigators were able to reliably detect telomerase activity in as few as 10 to 1,000 tumor cells grown in culture. The researchers then showed that they could detect changes in telomerase activity after the addition of a known inhibitor of the enzyme, suggesting that this assay could help in efforts to develop telomerase inhibitors as anticancer agents.
About National Cancer Institute
To help meet the goal of reducing the burden of cancer, the National Cancer Institute (NCI), part of the National Institutes of Health, is engaged in efforts to harness the power of nanotechnology to radically change the way we diagnose, treat and prevent cancer.
The NCI Alliance for Nanotechnology in Cancer is a comprehensive, systematized initiative encompassing the public and private sectors, designed to accelerate the application of the best capabilities of nanotechnology to cancer.
Currently, scientists are limited in their ability to turn promising molecular discoveries into benefits for cancer patients. Nanotechnology can provide the technical power and tools that will enable those developing new diagnostics, therapeutics, and preventives to keep pace with today’s explosion in knowledge.
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