2011
DOI: 10.1089/nat.2011.0313
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Rational Truncation of an RNA Aptamer to Prostate-Specific Membrane Antigen Using Computational Structural Modeling

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 tria… Show more

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Cited by 110 publications
(91 citation statements)
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References 67 publications
(86 reference statements)
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“…We chemically synthesized a 43 nucleotide minimized version of A9 (denoted here as A9.min) based on the minimal sequence reported by Archemix [14] and more recently reported by Rockey et al [15]. The same minimized sequence was identified from an analysis of a doped selection performed by our own group using a library based on the fulllength A9 ( [16] and unpublished results).…”
Section: Resultsmentioning
confidence: 99%
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“…We chemically synthesized a 43 nucleotide minimized version of A9 (denoted here as A9.min) based on the minimal sequence reported by Archemix [14] and more recently reported by Rockey et al [15]. The same minimized sequence was identified from an analysis of a doped selection performed by our own group using a library based on the fulllength A9 ( [16] and unpublished results).…”
Section: Resultsmentioning
confidence: 99%
“…The same minimized sequence was identified from an analysis of a doped selection performed by our own group using a library based on the fulllength A9 ( [16] and unpublished results). Because the bulk of the reported characterization of this aptamer relied on the inhibition of the enzymatic activity of PSMA [14,15], we initially preformed a cell-based analysis by flow cytometry to confirm the specificity and determine the apparent binding constant for this molecule on PSMA-positive cells.…”
Section: Resultsmentioning
confidence: 99%
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“…Its molecular weight was significantly reduced, but it still has very good binding affinity to PSMA. 24,25 On the basis of previous studies on NBs carrying anti-PSMA monoclonal antibodies and nanobodies, this study aimed to couple the A10-3.2 aptamer as a ligand with lipid NBs and to study its imaging effect in prostate cancer. The purpose was not only to provide ultrasound molecular probes with better safety, small particle size, strong penetration and specificity for prostate cancer, but also to provide methods for relevant studies on targeted ultrasound NBs carrying aptamers.…”
Section: Introductionmentioning
confidence: 99%
“…A9g is a truncated version of A9 that shows enhanced binding affinity to PSMA and, importantly, can inhibit its NAALADase/ glutamate carboxypeptidase II activity with an IC 50 of 10 nM (ref. 15). …”
mentioning
confidence: 99%