Duke University scientists demonstrated the possibility of using RNA aptamers to target tumor cells without affecting healthy tissue or activating the immune system. They did this on a mouse model by meticulously searching for a short strand aptemer that would bind to the specific tumor protein:
The researchers used a large pool of RNA strands and applied them to a rodent with a liver tumor, the type of metastatic tumor that often results from a colon cancer tumor.
“We hypothesized that the RNA molecules that bind to normal cellular elements would be filtered out, and this happened,” said Clary [Bryan Clary, MD, chief of the Division of Hepatopancreatobiliary and Oncologic Surgery –ed.], who treats colon cancer patients. “In this way, we found the RNA molecules that went specifically to the tumor.”
The researchers removed the tumor, extracted the specific RNA in the tumor, amplified these pieces of RNA to create a greater amount, and reinjected the molecules to learn which bound most tightly to the tumor. They repeated this process 14 times to find a good candidate.
The team found a tumor-targeting RNA aptamer that specifically bound to RNA helicase p68, a nuclear protein produced in colorectal tumors.
“This aptamer not only binds to p68 protein in cell culture, but also preferentially binds to cancer deposits in a living animal,” Mi said. “The nice thing about this aptamer approach is that it could be used to discover the molecular signatures of many other diseases.”
Clary said the process could be repeated with different types of tumors. For example, a scientist might take a breast cancer line and grow it in the lung as a metastasis model and then perform in vivo selection to identify RNAs specifically binding to the lung tumor.
Full story: First Live Targeting of Tumors with RNA-Based Technology…
Abstract in Nature Chemical Biology: In vivo selection of tumor-targeting RNA motifs
Image credit: Wellcome Images…
