Nanowire-Mediated Delivery Enables Functional Interrogation of Primary Immune Cells: Application to the Analysis of Chronic Lymphocytic Leukemia

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Nanowire-Mediated Delivery Enables Functional Interrogation of Primary Immune Cells: Application to the Analysis of Chronic Lymphocytic Leukemia

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Title: Nanowire-Mediated Delivery Enables Functional Interrogation of Primary Immune Cells: Application to the Analysis of Chronic Lymphocytic Leukemia
Author: Shalek, Alexander Kann; Gaublomme, Jellert Thomas; Wang, Lili; Yosef, Nir; Chevrier, Nicolas; Andersen, Mette S.; Robinson, Jacob T.; Pochet, Nathalie; Neuberg, Donna S.; Gertner, Rona S.; Amit, Ido; Brown, Jennifer Ruth; Hacohen, Nir; Regev, Aviv; Wu, Cathy Ju-Ying; Park, Hongkun

Note: Order does not necessarily reflect citation order of authors.

Citation: Shalek, Alex K., Jellert T. Gaublomme, Lili Wang, Nir Yosef, Nicolas Chevrier, Mette S. Andersen, Jacob T. Robinson, et al. 2012. Nanowire-mediated delivery enables functional interrogation of primary immune cells: application to the analysis of chronic lymphocytic leukemia. Nano Letters 12(12): 6498-6504.
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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.
Published Version: doi:10.1021/nl3042917
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3573729/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:11726250
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