Cited by 139RNA and protein synthesis mechanismsRNA Interference and Gene DeliveryAdvanced biosensing and bioanalysis techniques

Rational Truncation of an RNA Aptamer to Prostate-Specific Membrane Antigen Using Computational Structural Modeling

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Rockey, William M., Hernandez, Frank J., Huang, Sheng-You, Cao, Song, Howell, Craig A., Thomas, Gregory S., Liu, Xiu Ying, Lapteva, Natalia +5 more·2011·Nucleic Acid Therapeutics

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.

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Crossref · 10.1089/nat.2011.0313

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  • A9g aptamer has improved stability, reduced synthesis difficulty, and retains high-affinity binding to PSMA.

    “In order to obtain a shorter RNA aptamer, William M. Rockey et al. truncated the A9 aptamer to obtain the A9g aptamer, which improved the stability of the aptamer and reduced the difficulty of synthesis, while retaining the high-affinity binding ability to PSMA.246”

    From Smart nanoparticles for cancer therapy (2023) · cites this paper as [246]

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Authors
Rockey, W. M., Hernandez, F. J., Huang, S.-Y., Cao, S., Howell, C. A., Thomas, G. S., Liu, X. Y., Lapteva, N., Spencer, D. M., Mcnamara, J. O., Zou, X., Chen, S.-J., & Giangrande, P. H.
Affiliations
  • University of Iowa (US)
  • University of Iowa
  • University of Missouri (US)
  • Baylor College of Medicine (US)
Corresponding author
Giangrande, Paloma H.
Venue
Nucleic Acid Therapeutics
Published
2011-10-01
Volume
21
Issue
5
Pages
299-314
ISSN
  • 2159-3337 (ISSN-L)
  • 2159-3345
OpenAlex
W2078728864
Cited by
139
References
73
Citations by year
2026: 2 · 2025: 13 · 2024: 10 · 2023: 13 · 2022: 10 · 2021: 8 · 2020: 7 · 2019: 8 · 2018: 10 · 2017: 13 · 2016: 15 · 2015: 8 · 2014: 10 · 2013: 7 · 2012: 5
FWCI
2.86
Type
journal article
Language
en
Open access
Locations
  • Nucleic Acid Therapeutics (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Science Foundation (0953839, 0920411, 0920067, CAREER)
  • Roy J. Carver Charitable Trust (01-224, RJCCT 01-224)
  • Radiological Society of North America
  • National Institutes of Health
  • National Cancer Institute (R01CA138503)
  • National Institute of General Medical Sciences (GM 063732, R01GM063732, R21GM088517)
  • National Institute of Dental and Craniofacial Research (R21DE019953)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Advanced biosensing and bioanalysis techniques
Keywords
RNA aptamers, prostate-specific membrane antigen, aptamer therapeutics, RNA tertiary structure prediction, protein-RNA docking, targeted cancer therapy
MeSH terms
Computer Simulation, Humans, Male, Models, Molecular, Nucleic Acid Conformation, Prostatic Neoplasms, Protein Binding, Recombinant Proteins, Structure-Activity Relationship, Drug Design, Surface Plasmon Resonance, Protein Transport, Glutamate Carboxypeptidase II, Cell Line, Tumor, Aptamers, Nucleotide, Enzyme Assays

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