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Cited by 589

The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.

Systemic administration of optimized aptamer-siRNA chimeras promotes regression of PSMA-expressing tumors

Open access
Dassie, Justin P, Liu, Xiu-ying, Thomas, Gregory S, Whitaker, Ryan M, Thiel, Kristina W, Stockdale, Katie R, Meyerholz, David K, McCaffrey, Anton P, McNamara, James O, Giangrande, Paloma H·2009·Nature Biotechnology

Abstract

Prostate cancer cells expressing prostate-specific membrane antigen (PSMA) have been targeted with RNA aptamer–small interfering (si)RNA chimeras, but therapeutic efficacy in vivo was demonstrated only with intratumoral injection. Clinical translation of this approach will require chimeras that are effective when administered systemically and are amenable to chemical synthesis. To these ends, we enhanced the silencing activity and specificity of aptamer-siRNA chimeras by incorporating modifications that enable more efficient processing of the siRNA by the cellular machinery. These included adding 2-nucleotide 3′-overhangs and optimizing the thermodynamic profile and structure of the duplex to favor processing of the siRNA guide strand. We also truncated the aptamer portion of the chimeras to facilitate large-scale chemical synthesis. The optimized chimeras resulted in pronounced regression of PSMA-expressing tumors in athymic mice after systemic administration. Anti-tumor activity was further enhanced by appending a polyethylene glycol moiety, which increased the chimeras' circulating half-life.

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Metadata

Authors
Dassie, J. P., Liu, X.-Y., Thomas, G. S., Whitaker, R. M., Thiel, K. W., Stockdale, K. R., Meyerholz, D. K., McCaffrey, A. P., McNamara, J. O., & Giangrande, P. H.
Venue
Nature Biotechnology
Published
2009-08-23
Volume
27
Issue
9
Pages
839-846
ISSN
  • 0733-222X (ISSN-L)
  • 1087-0156
  • 1546-1696
OpenAlex
W2149147994
Cited by
589
References
2
FWCI
18.36
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Systemic administration of optimized aptamer-siRNA chimeras promotes regression of PSMA-expressing tumors. https://app.cochat.ai/papers/10.1038/nbt.1560
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Dassie, J. P., Liu, X.-Y., Thomas, G. S., Whitaker, R. M., Thiel, K. W., Stockdale, K. R., Meyerholz, D. K., McCaffrey, A. P., McNamara, J. O., & Giangrande, P. H. (2009). Systemic administration of optimized aptamer-siRNA chimeras promotes regression of PSMA-expressing tumors. Nature Biotechnology. https://doi.org/10.1038/nbt.1560

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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