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

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • McNamara, JO; Andrechek, ER; Wang, Y; Viles, KD; Rempel, RE; Gilboa, E; Sullenger, BA; Giangrande, PH

Published Date

  • August 2006

Published In

Volume / Issue

  • 24 / 8

Start / End Page

  • 1005 - 1015

PubMed ID

  • 16823371

International Standard Serial Number (ISSN)

  • 1087-0156

Digital Object Identifier (DOI)

  • 10.1038/nbt1223

Language

  • eng

Conference Location

  • United States