Structured functional RNA entities, including aptamers and siRNAs, have amazing versatility in structure and function. These molecules can serve as powerful, attractive building blocks for the bottom-up assembly of complex nanostructures. Here, we describe novel cell-type specific and internalizing B-cell activating factor receptor (BAFF-R) aptamer–siRNA delivery systems for B-cell lymphoma therapy, in which both the aptamer and the Dicer substrate siRNA (DsiRNA) portions are conjugated through a “sticky bridge.” The BAFF-R is overexpressed on the surface of B-cell malignancies, allowing binding and internalization of the aptamer–stick–siRNA nanoparticles. STAT3 siRNAs are encapsulated within the nanoparticles delivered by the BAFF-R aptamers and are localized to the cytoplasm, resulting in robust gene silencing of STAT3 mRNAs in a variety of B-cell lines. Moreover, these nanoparticles do not induce cell proliferation and apoptosis. Collectively, aptamer-mediated delivery strategies provide a toolset to become a more widely used therapeutic modality for the treatment of diseases.
CITATION STYLE
Zhou, J., Rossi, J. J., & Shum, K. T. (2015). Methods for assembling b-cell lymphoma specific and internalizing aptamer–siRNA nanoparticles via the sticky bridge. Methods in Molecular Biology, 1297, 169–185. https://doi.org/10.1007/978-1-4939-2562-9_12
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