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Targeted inhibition of prostate cancer metastases with an RNA aptamer to prostate-specific membrane antigen
Department of Internal Medicine, University of of Iowa, 375 Newton Rd, 5202 MERF, Iowa City, IA, United States.
Department of Internal Medicine, University of of Iowa, 375 Newton Rd, 5202 MERF, Iowa City, IA, United States.
Department of Internal Medicine, University of of Iowa, 375 Newton Rd, 5202 MERF, Iowa City, IA, United States.
Molecular and Cellular Biology Program, University of of Iowa, Iowa City, IA, United States; Inflammation Program, University of of Iowa, Iowa City, IA, United States.
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2014 (English)In: Molecular Therapy, ISSN 1525-0016, E-ISSN 1525-0024, Vol. 22, no 11, 1910-1922 p.Article in journal (Refereed) Published
Abstract [en]

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. © The American Society of Gene amp; Cell Therapy.

Place, publisher, year, edition, pages
Nature Publishing Group, 2014. Vol. 22, no 11, 1910-1922 p.
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:liu:diva-143330DOI: 10.1038/mt.2014.117ISI: 000344429800009PubMedID: 24954476Scopus ID: 2-s2.0-84964313160OAI: oai:DiVA.org:liu-143330DiVA: diva2:1162485
Note

Funding Agencies|T32HL07344, NIH, National Institutes of Health; NIH, National Institutes of Health; 001-09, TMKF, Mary Kay Foundation; 9033-12, TMKF, Mary Kay Foundation; R01CA138503, NIH, National Institutes of Health; R21DE019953, NIH, National Institutes of Health

Available from: 2017-12-04 Created: 2017-12-04 Last updated: 2017-12-12Bibliographically approved

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Hernandez, Luiza I.Hernandez, Frank J

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