Novel Method Uses Living Tumors to Screen for Anticancer Aptamers

Cancer researchers have used tumors growing in laboratory mice as a screening mechanism to select and isolate an RNA aptamer that could bind to and specifically inhibit a protein critical for the tumor's growth.

Nucleic acid aptamers are nucleic acid species that have been engineered through repeated rounds of in vitro selection to bind to various molecular targets such as small molecules, proteins, nucleic acids, and even cells, tissues and organisms. Aptamers are useful in biotechnological and therapeutic applications as they offer molecular recognition properties that rival that of antibodies. In addition to their discriminate recognition, aptamers offer advantages over antibodies as they can be engineered completely in a test tube, are readily produced by chemical synthesis, possess desirable storage properties, and elicit little or no immunogenicity in therapeutic applications.

Investigators at Duke University Medical Center (Durham, NC, USA) screened a large library of nuclease-resistant RNA oligonucleotides in tumor-bearing mice to identify candidate molecules with the ability to localize to hepatic colon cancer metastases. This work represents a novel in vivo approach to aptamer screening.

The authors reported in the November 29, 2009, online edition of the journal Nature Chemical Biology that after 14 cycles of screening and enrichment they isolated an aptamer specific for p68, an RNA helicase enzyme that had been shown to be upregulated in colorectal cancer. The aptamer, which may be a starting point for future drug development, not only bound to p68 protein in cell cultures, it also preferentially bound to cancer deposits in living animals.

"We hypothesized that the RNA molecules that bind to normal cellular elements would be filtered out, and this happened," said senior author Dr. Bryan Clary, professor of oncologic surgery at Duke University Medical Center. "In this way, we found the RNA molecules that went specifically to the tumor."

"We are already exploring attaching chemicals to the aptamers, so the aptamer molecules could deliver tumor-killing agents where they are needed, which is the next phase of our research," said Dr. Clary. "The idea of selecting molecules targeting a tumor growing in a body that results in a useful reagent for biologic exploration and therapy delivery in tumors is exciting."

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