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Rational truncation of an RNA aptamer to prostate-specific membrane antigen using computational structural modeling
Department of Radiation Oncology, University of of Iowa, Iowa City, IA, United States.
Department of Internal Medicine, University of of Iowa, 285 Newton Road, Iowa City, IA 52242, United States.
Departments of Physics and Astronomy, United States; Department of Biochemistry, University of of Missouri, Columbia, MO, United States; Dalton Cardiovascular Research Center, University of of Missouri, Columbia, MO, United States; Informatics Institute, University of of Missouri, Columbia, MO, United States.
Departments of Physics and Astronomy, United States; Department of Biochemistry, University of of Missouri, Columbia, MO, United States; Informatics Institute, University of of Missouri, Columbia, MO, United States.
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2011 (English)In: Nucleic Acid Therapeutics, ISSN 2159-3337, E-ISSN 2159-3345, Vol. 21, no 5, 299-314 p.Article in journal (Refereed) Published
Abstract [en]

RNA aptamers represent an emerging class of pharmaceuticals with great potential for targeted cancer diagnostics and therapy. Several RNA aptamers that bind cancer cell-surface antigens with high affinity and specificity have been described. However, their clinical potential has yet to be realized. A significant obstacle to the clinical adoption of RNA aptamers is the high cost of manufacturing long RNA sequences through chemical synthesis. Therapeutic aptamers are often truncated postselection by using a trial-and-error process, which is time consuming and inefficient. Here, we used a rational truncation approach guided by RNA structural prediction and protein/RNA docking algorithms that enabled us to substantially truncateA9, an RNA aptamer to prostate-specific membrane antigen (PSMA),with great potential for targeted therapeutics. This truncated PSMA aptamer (A9L; 41mer) retains binding activity, functionality, and is amenable to large-scale chemical synthesis for future clinical applications. In addition, the modeled RNA tertiary structure and protein/RNA docking predictions revealed key nucleotides within the aptamer critical for binding to PSMA and inhibiting its enzymatic activity. Finally, this work highlights the utility of existing RNA structural prediction and protein docking techniques that may be generally applicable to developing RNA aptamers optimized for therapeutic use. © 2011 Mary Ann Liebert, Inc.

Place, publisher, year, edition, pages
Mary Ann Liebert, 2011. Vol. 21, no 5, 299-314 p.
National Category
Biochemistry and Molecular Biology
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URN: urn:nbn:se:liu:diva-143340DOI: 10.1089/nat.2011.0313ISI: 000296231700131PubMedID: 22004414Scopus ID: 2-s2.0-80054730117OAI: oai:DiVA.org:liu-143340DiVA: diva2:1162516
Available from: 2017-12-04 Created: 2017-12-04 Last updated: 2017-12-13Bibliographically approved

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Hernandez, Frank J

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