Research abstract

Article abstract


Nature Biotechnology 24, 1005 - 1015 (2006)
Published online: 25 June 2006 | doi:10.1038/nbt1223

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

James O McNamara II1,3, Eran R Andrechek2,3, Yong Wang1, Kristi D Viles1, Rachel E Rempel2, Eli Gilboa1, Bruce A Sullenger1 & Paloma H Giangrande1


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.

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  1. Duke Center for Translational Research, Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
  2. Duke Institute for Genome Sciences and Policy, Duke University Medical Center, Durham, North Carolina 27710, USA.
  3. These authors contributed equally to this work.

Correspondence to: Bruce A Sullenger1 e-mail: b.sullenger@cgct.duke.edu



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