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 accessAbstract
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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Rational siRNA design for RNA interference
Reynolds, A., Leake, D., Boese, Q., Scaringe, S., Marshall, W. S., & Khvorova, A. (2004) · Nature Biotechnology · doi:10.1038/nbt936 · Cited by 2,094
Transvascular delivery of small interfering RNA to the central nervous system
Kumar, P., Wu, H., McBride, J. L., Jung, K.-E., Hee Kim, M., Davidson, B. L., Kyung Lee, S., Shankar, P., & Manjunath, N. (2007) · Nature · doi:10.1038/nature05901 · Cited by 1,246
Cited by
Keefe, A. D., Pai, S., & Ellington, A. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3141 · Cited by 2,289
Delivery materials for siRNA therapeutics
Kanasty, R., Dorkin, J. R., Vegas, A., & Anderson, D. (2013) · Nature Materials · doi:10.1038/nmat3765 · Cited by 1,800
The delivery of therapeutic oligonucleotides
Juliano, R. L. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw236 · Cited by 854
Aptamer-based targeted therapy
Zhu, G., & Chen, X. (2018) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2018.08.005 · Cited by 522
Silencing disease genes in the laboratory and the clinic
Watts, J. K., & Corey, D. R. (2012) · The Journal of Pathology · doi:10.1002/path.2993 · Cited by 470
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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- 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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