Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras

James O. McNamara, Eran R. Andrechek, Yong Wang, Kristi D. Viles, Rachel E. Rempel, Eli Gilboa, Bruce A. Sullenger, Paloma H. Giangrande

Research output: Contribution to journalArticle

740 Citations (Scopus)

Abstract

Technologies that mediate targeted delivery of small interfering RNAs (siRNAs) are needed to improve their therapeutic efficacy and safety. Therefore, we have developed aptamer-siRNA chimeric RNAs capable of cell type-specific binding and delivery of functional siRNAs into cells. The aptamer portion of the chimeras mediates binding to PSMA, a cell-surface receptor overexpressed in prostate cancer cells and tumor vascular endothelium, whereas the siRNA portion targets the expression of survival genes. When applied to cells expressing PSMA, these RNAs are internalized and processed by Dicer, resulting in depletion of the siRNA target proteins and cell death. In contrast, the chimeras do not bind to or function in cells that do not express PSMA. These reagents also specifically inhibit tumor growth and mediate tumor regression in a xenograft model of prostate cancer. These studies demonstrate an approach for targeted delivery of siRNAs with numerous potential applications, including cancer therapeutics.

Original languageEnglish
Pages (from-to)1005-1015
Number of pages11
JournalNature Biotechnology
Volume24
Issue number8
DOIs
StatePublished - Aug 1 2006
Externally publishedYes

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Nucleotide Aptamers
RNA
Small Interfering RNA
Tumors
Cells
Neoplasms
Prostatic Neoplasms
Cell death
Vascular Endothelium
Cell Surface Receptors
Heterografts
Genes
Proteins
Cell Death
Technology
Safety
Gene Expression
Therapeutics
Growth

ASJC Scopus subject areas

  • Microbiology

Cite this

McNamara, J. O., Andrechek, E. R., Wang, Y., Viles, K. D., Rempel, R. E., Gilboa, E., ... Giangrande, P. H. (2006). Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras. Nature Biotechnology, 24(8), 1005-1015. https://doi.org/10.1038/nbt1223

Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras. / McNamara, James O.; Andrechek, Eran R.; Wang, Yong; Viles, Kristi D.; Rempel, Rachel E.; Gilboa, Eli; Sullenger, Bruce A.; Giangrande, Paloma H.

In: Nature Biotechnology, Vol. 24, No. 8, 01.08.2006, p. 1005-1015.

Research output: Contribution to journalArticle

McNamara, JO, Andrechek, ER, Wang, Y, Viles, KD, Rempel, RE, Gilboa, E, Sullenger, BA & Giangrande, PH 2006, 'Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras', Nature Biotechnology, vol. 24, no. 8, pp. 1005-1015. https://doi.org/10.1038/nbt1223
McNamara JO, Andrechek ER, Wang Y, Viles KD, Rempel RE, Gilboa E et al. Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras. Nature Biotechnology. 2006 Aug 1;24(8):1005-1015. https://doi.org/10.1038/nbt1223
McNamara, James O. ; Andrechek, Eran R. ; Wang, Yong ; Viles, Kristi D. ; Rempel, Rachel E. ; Gilboa, Eli ; Sullenger, Bruce A. ; Giangrande, Paloma H. / Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras. In: Nature Biotechnology. 2006 ; Vol. 24, No. 8. pp. 1005-1015.
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