Targeted Inhibition of Prostate Cancer Metastases with an RNA Aptamer to Prostate-specific Membrane Antigen |
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| Authors: | Justin P Dassie Luiza I Hernandez Gregory S Thomas Matthew E Long William M Rockey Craig A Howell Yani Chen Frank J Hernandez Xiu Ying Liu Mary E Wilson Lee-Ann Allen Daniel A Vaena David K Meyerholz Paloma H Giangrande |
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| Institution: | 1. Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA;2. Molecular and Cellular Biology Program, University of Iowa, Iowa City, Iowa, USA;3. Inflammation Program, University of Iowa, Iowa City, Iowa, USA;4. Department of Radiation Oncology, University of Iowa, Iowa City, Iowa, USA;5. Department of Microbiology, University of Iowa, Iowa City, Iowa, USA;6. Veteran''s Affairs Medical Center, University of Iowa, Iowa City, Iowa, USA;7. Department of Pathology, University of Iowa, Iowa City, Iowa, USA |
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| Abstract: | Cell-targeted therapies (smart drugs), which selectively control cancer cell progression with limited toxicity to normal cells, have been developed to effectively treat some cancers. However, many cancers such as metastatic prostate cancer (PC) have yet to be treated with current smart drug technology. Here, we describe the thorough preclinical characterization of an RNA aptamer (A9g) that functions as a smart drug for PC by inhibiting the enzymatic activity of prostate-specific membrane antigen (PSMA). Treatment of PC cells with A9g results in reduced cell migration/invasion in culture and metastatic disease in vivo. Importantly, A9g is safe in vivo and is not immunogenic in human cells. Pharmacokinetic and biodistribution studies in mice confirm target specificity and absence of non-specific on/off-target effects. In conclusion, these studies provide new and important insights into the role of PSMA in driving carcinogenesis and demonstrate critical endpoints for the translation of a novel RNA smart drug for advanced stage PC. |
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