Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras - PubMed (original) (raw)
. 2006 Aug;24(8):1005-15.
doi: 10.1038/nbt1223. Epub 2006 Jun 25.
Affiliations
- PMID: 16823371
- DOI: 10.1038/nbt1223
Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras
James O McNamara 2nd et al. Nat Biotechnol. 2006 Aug.
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.
Comment in
- All in the RNA family.
Davidson BL. Davidson BL. Nat Biotechnol. 2006 Aug;24(8):951-2. doi: 10.1038/nbt0806-951. Nat Biotechnol. 2006. PMID: 16900139 No abstract available. - Conjugates of small targeting molecules to non-viral vectors for the mediation of siRNA.
Zhi D, Zhao Y, Cui S, Chen H, Zhang S. Zhi D, et al. Acta Biomater. 2016 May;36:21-41. doi: 10.1016/j.actbio.2016.03.048. Epub 2016 Apr 1. Acta Biomater. 2016. PMID: 27045350 Review.
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