Nanowire-Mediated Delivery Enables Functional Interrogation of Primary Immune Cells: Application to the Analysis of Chronic Lymphocytic Leukemia
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Shalek_2012-Nanowire-mediated delivery.pdf
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Author(s)
Shalek, Alex K.
Gaublomme, Jellert T.
Wang, Lili
Yosef, Nir
Chevrier, Nicolas
Andersen, Mette S.
Robinson, Jacob T.
Pochet, Nathalie
Neuberg, Donna S.
Gertner, Rona S.
Date Issued
November 2012
Journal
Nano Letters
Publisher
American Chemical Society (ACS)
Citation
Shalek, Alex K., Jellert T. Gaublomme, Lili Wang, Nir Yosef, Nicolas Chevrier, Mette S. Andersen, Jacob T. Robinson, et al. “Nanowire-Mediated Delivery Enables Functional Interrogation of Primary Immune Cells: Application to the Analysis of Chronic Lymphocytic Leukemia.” Nano Letters 12, no. 12 (December 12, 2012): 6498-6504. © 2012 American Chemical Society
Version
Final published version
Abstract
A circuit level understanding of immune cells and hematological cancers has been severely impeded by a lack of techniques that enable intracellular perturbation without significantly altering cell viability and function. Here, we demonstrate that vertical silicon nanowires (NWs) enable gene-specific manipulation of diverse murine and human immune cells with negligible toxicity. To illustrate the power of the technique, we then apply NW-mediated gene silencing to investigate the role of the Wnt signaling pathway in chronic lymphocytic leukemia (CLL). Remarkably, CLL-B cells from different patients exhibit tremendous heterogeneity in their response to the knockdown of a single gene, LEF1. This functional heterogeneity defines three distinct patient groups not discernible by conventional CLL cytogenetic markers and provides a prognostic indicator for patients’ time to first therapy. Analyses of gene expression signatures associated with these functional patient subgroups reveal unique insights into the underlying molecular basis for disease heterogeneity. Overall, our findings suggest a functional classification that can potentially guide the selection of patient-specific therapies in CLL and highlight the opportunities for nanotechnology to drive biological inquiry.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1021/nl3042917
