Journal article
Rational Truncation of an RNA Aptamer to Prostate-Specific Membrane Antigen Using Computational Structural Modeling
Nucleic acid therapeutics, Vol.21(5), pp.299-314
10/01/2011
DOI: 10.1089/nat.2011.0313
PMCID: PMC3198747
PMID: 22004414
Abstract
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.
Details
- Title: Subtitle
- Rational Truncation of an RNA Aptamer to Prostate-Specific Membrane Antigen Using Computational Structural Modeling
- Creators
- William M Rockey - 1Department of Radiation Oncology, University of Iowa, Iowa City, IowaFrank J Hernandez - 2Department of Internal Medicine, University of Iowa, Iowa City, IowaSheng-You Huang - 6Informatics Institute, University of Missouri, Columbia, MissouriSong Cao - 6Informatics Institute, University of Missouri, Columbia, MissouriCraig A Howell - 2Department of Internal Medicine, University of Iowa, Iowa City, IowaGregory S Thomas - 7Molecular and Cellular Biology Program, University of Iowa, Iowa City, IowaXiu Ying Liu - 2Department of Internal Medicine, University of Iowa, Iowa City, IowaNatalia Lapteva - 8Department of Pathology and Immunology, Baylor College of Medicine, Houston, TexasDavid M Spencer - 8Department of Pathology and Immunology, Baylor College of Medicine, Houston, TexasJames O McNamara - 2Department of Internal Medicine, University of Iowa, Iowa City, IowaXiaoqin Zou - 6Informatics Institute, University of Missouri, Columbia, MissouriShi-Jie Chen - 6Informatics Institute, University of Missouri, Columbia, MissouriPaloma H Giangrande - 7Molecular and Cellular Biology Program, University of Iowa, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- Nucleic acid therapeutics, Vol.21(5), pp.299-314
- DOI
- 10.1089/nat.2011.0313
- PMID
- 22004414
- PMCID
- PMC3198747
- NLM abbreviation
- Nucleic Acid Ther
- ISSN
- 2159-3337
- eISSN
- 2159-3345
- Publisher
- Mary Ann Liebert, Inc
- Language
- English
- Date published
- 10/01/2011
- Academic Unit
- Radiation Oncology; Medicine Administration; Internal Medicine
- Record Identifier
- 9984047602102771
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