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Methods for Assembling B-Cell Lymphoma Specific and Internalizing Aptamer–siRNA Nanoparticles Via the Sticky Bridge

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RNA Nanotechnology and Therapeutics

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1297))

Abstract

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.

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Acknowledgements

We thank Britta Hoehn for helping with the design of the RNA-library and primers. We thank Marcin Kortylewski for providing the sequences of human STAT3 DsiRNA and primers for qRT-PCR. This work was supported by grants from the Nesvig Lymphoma Foundation, Think Cure, and the Keck Foundation. This work also was supported by the National Institutes of Health grants P50CA107399 awarded to J.J.R and Stephen Forman (Beckman Research Institute of City of Hope); R37AI029329 awarded to J.J.R.; U01CA151648 awarded to Peixuan Guo (University of Kentucky) and subcontracted to J.J.R; and K12CA001727 for which Robert Chen (Beckman Research Institute of City of Hope) is a trainee. Conflict of Interest declaration: J.J.R. and J.Z. have an issued patent entitled “Cell-type specific aptamer-siRNA delivery system for HIV-1 therapy.” USPTO no: US 8, 222, 226 B2. Issued date: July 17, 2012. J.J.R. and J.Z. have a patent pending on “RNA aptamers against BAFF-R as cell-type specific delivery agents and methods for their use.” USPTO no: US2011/032385. Publication date: Oct 20, 2011.

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Authors and Affiliations

  1. Department of Molecular and Cellular Biology, Irell and Manella Graduate School of Biological Sciences, Beckman Research Institute of City of Hope, 1500 East Duarte Road, Duarte, CA, USA

    John J. Rossi

  2. Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, 1500 East Duarte Road, Duarte, CA, USA

    Jiehua Zhou & Ka To Shum

Authors
  1. Jiehua Zhou
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  2. John J. Rossi
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  3. Ka To Shum
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Corresponding author

Correspondence to John J. Rossi .

Editor information

Editors and Affiliations

  1. Nanobiotechnology Center, Markey Cancer Center, Department of Pharmaceutical Sciences, University of Kentucky, Lexington, Kentucky, USA

    Peixuan Guo

  2. Nanobiotechnology Center, Markey Cancer Center, Department of Pharmaceutical Sciences, University of Kentucky, Lexington, Kentucky, USA

    Farzin Haque

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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. In: Guo, P., Haque, F. (eds) RNA Nanotechnology and Therapeutics. Methods in Molecular Biology, vol 1297. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2562-9_12

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  • DOI: https://doi.org/10.1007/978-1-4939-2562-9_12

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-2561-2

  • Online ISBN: 978-1-4939-2562-9

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