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RNA Aptamers Deliver Chemotherapy Directly to Tumors.

Scientists have harnessed synthetic RNA molecules that behave like antibodies—with high affinity and specificity for a target—to shuttle chemotherapy agents directly into tumors. The drug delivery strategy employs RNA aptamers, whose etymology stems from the Greek word aptus, meaning “to fit.” These short-stranded nucleic acid molecules are easy to engineer, nonimmunogenic, and thanks to their small size can penetrate deep within tissues. The US Food and Drug Administration approved the first RNA aptamer, pegaptanib (marketed as Macugen), in 2004 to treat patients with age-related macular degeneration. Since then, scientists have been testing their potential as diagnostic, prognostic, and therapeutic tools for a range of diseases. Investigators recently identified 4 RNA aptamers that bind to molecules on the surface of cancer-promoting immune cells. These so-called myeloid-derived suppressor cells accumulate within tumors and support cancer cell survival by suppressing antitumor immune responses. The new drug delivery approach, described in Science Translational Medicine, turns this harmful process on its head. In an interview, senior author Paolo Serafini, PhD, said the study grew out of “the idea to transform these immune cells to become our allies and deliver therapeutics specifically to the tumor site.” Because myeloid-derived suppressor cells are similar across patients and malignancies, “an agent that targets them has the potential to be universal and work for most patients with solid tumors,” said Serafini, an assistant professor of microbiology and immunology at the University of Miami Miller School of Medicine’s Sylvester Comprehensive Cancer Center. To find the RNA aptamers, his team used a sophisticated method to create billions of random sequences and then subject them to multiple rounds of selection with increasing stringency, thus mimicking an evolutionary process in the laboratory. Importantly, in multiple mouse models and cells from patients with head and neck squamous cell carcinoma, the aptamers they identified recognized only tumor-infiltrating myeloid cells and not their peripheral or circulating counterparts. This finding offers preliminary reassurance that the treatment could be generally safe and nontoxic.