Publications [#177514] of Bruce A Sullenger

Papers Published

1. JO McNamara 2nd, ER Andrechek, Y Wang, KD Viles, RE Rempel, E Gilboa, BA Sullenger, PH Giangrande, Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras., Nature biotechnology, vol. 24 no. 8 (August, 2006), pp. 1005-15, ISSN 1087-0156 [doi]
   (last updated on 2013/05/16)

   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.

   Keywords:
   Animals • Aptamers, Nucleotide • Cell Line, Tumor • Gene Silencing* • Gene Targeting • Gene Transfer Techniques* • Humans • RNA, Small Interfering • administration & dosage • administration & dosage* • genetics* • methods*