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


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2006-08

AUTHORS

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

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. More... »

PAGES

1005-1015

Journal

TITLE

Nature Biotechnology

ISSUE

8

VOLUME

24

Author Affiliations

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nbt1223

    DOI

    http://dx.doi.org/10.1038/nbt1223

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1038778955

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/16823371


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