Using cell-SELEX to identify 2'F-modified RNA aptamers that specifically target pancreatic cancer.

 

Trainee:

Sarah Claypool

Sarah Claypool

Research Mentor:

Dr. Rihe Liu

unavailable

Clinical Co-Mentor:

Dr. Young Whang

unavailable
Department Medicinal Chemistry and Natural Products
Project Description:

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer death in the United States with a dismal 5-year survival of 5%. This is largely due to the fact that it is hard to diagnose the cancer early due to the relatively asymptomatic nature of pancreatic cancer. It is therefore the long-term goal of this project to identify novel biomarkers to aid in early diagnosis of PDAC as well as to develop targeting ligands for these biomarkers as potential means of targeted therapy. We aim to systematically identify 2’-fluoro modified RNA aptamers that selectively and effectively bind to novel biomarkers on the cell-surface of PDAC cells without binding to normal pancreas cells and non-pancreatic cells; and that such aptamers can be used for diagnosis and potentially therapeutic purposes. From the series of aptamers that show selective binding to PDAC cells, we will characterize and optimize the aptamers by identifying their sequences and testing their cell-surface binding features. We have already expanded this cell-surface binding study by using immunohistochemistry on patient-derived tissue samples, to show that the aptamers can selectively bind to human tissue as well as cells. Second, we are using the strong binding capability of the optimized aptamer to isolate and identify the unknown cell-surface biomarker that we have observed to be present on PDAC cell lines. Seeing that there are very few biomarkers known for pancreatic cancer, this novel biomarker identification will aid in a future diagnostic tests that are of great need. Lastly, we will choose our best RNA aptamer to label with a near IR fluorescent dye and test with orthotopic PDAC mouse models. These studies will demonstrate the tumor targeting capability of the aptamer for in vivo imaging applications as well as for potential therapeutic applications.